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Adalimumab

Phase 3

Ankylosing Spondylitis | Small molecule | Immunology |Abbott Laboratories|Last Updated: Nov 7, 2019

Target and mechanism

ModalitySmall molecule

Also known as Adalimumab (D2E7), Double-blind adalimumab, adalimumab (Humira), adalimumab (D2E7), Humira (adalimumab), Humira, Adalimumab (Humira)

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials5
Total Enrollment2,032

FDA Designations

No designations recorded

Clinical trial landscape

Adalimumab · 56 trials · 16 indications

Phase 3 41Phase 2 15
NCT01497717Efficacy of Humira in Behcet Patients With ArthritisArthritis; Behcet
COMPLETED9 Analytics
NCT01295814Efficacy Study of Adalimumab to Treat Interstitial CystitisInterstitial Cystitis
COMPLETED43 Analytics
NCT00660647Optimized Treatment Algorithm for Patients With Early Rheumatoid Arthritis (RA)Arthritis, Rheumatoid
COMPLETED180 Analytics
NCT01114880Efficacy and Safety of Adalimumab in Adult Chinese Subjects With Active Ankylosing SpondylitisAnkylosing Spondylitis
COMPLETED344 Analytics
NCT00870467A Study of Adalimumab in Japanese Subjects With Rheumatoid ArthritisRheumatoid Arthritis
COMPLETED334 Analytics
NCT00690573Safety, Efficacy, and Pharmacokinetics of Adalimumab in Japanese Children With Juvenile Rheumatoid ArthritisJuvenile Rheumatoid Arthritis
COMPLETED25 Analytics
NCT00667355A Study of Adalimumab in Japanese Subjects With Active Ankylosing SpondylitisAnkylosing Spondylitis
COMPLETED41 Analytics
NCT00566722Open Label Study of Adalimumab in Subjects Who Have a Sub-optimal Response to Systemic Therapy or PhototherapyPsoriasis
COMPLETED152 Analytics
NCT01231321A Study of Adalimumab When Added to Inadequate Standard Anti-rheumatic Therapy in Patients With Active Rheumatoid ArthritisRheumatoid Arthritis
COMPLETED100 Analytics
NCT00647270Study Comparing 80 mg of Adalimumab With Placebo, and Demonstrating the Non-inferiority of Monthly 80 mg Adalimumab Dosing Compared With 40 mg Adalimumab Every Other Week DosingRheumatoid Arthritis
COMPLETED420 Analytics
PHASE3COMPLETED
Efficacy of Humira in Behcet Patients With Arthritis
Arthritis; BehcetUnlock trial analytics
PHASE3COMPLETED
Efficacy Study of Adalimumab to Treat Interstitial Cystitis
Interstitial CystitisUnlock trial analytics
PHASE3COMPLETED
Optimized Treatment Algorithm for Patients With Early Rheumatoid Arthritis (RA)
Arthritis, RheumatoidUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety of Adalimumab in Adult Chinese Subjects With Active Ankylosing Spondylitis
Ankylosing SpondylitisUnlock trial analytics
PHASE3COMPLETED
A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis
Rheumatoid ArthritisUnlock trial analytics
PHASE3COMPLETED
Safety, Efficacy, and Pharmacokinetics of Adalimumab in Japanese Children With Juvenile Rheumatoid Arthritis
Juvenile Rheumatoid ArthritisUnlock trial analytics
PHASE3COMPLETED
A Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis
Ankylosing SpondylitisUnlock trial analytics
PHASE3COMPLETED
Open Label Study of Adalimumab in Subjects Who Have a Sub-optimal Response to Systemic Therapy or Phototherapy
PsoriasisUnlock trial analytics
PHASE3COMPLETED
A Study of Adalimumab When Added to Inadequate Standard Anti-rheumatic Therapy in Patients With Active Rheumatoid Arthritis
Rheumatoid ArthritisUnlock trial analytics
PHASE3COMPLETED
Study Comparing 80 mg of Adalimumab With Placebo, and Demonstrating the Non-inferiority of Monthly 80 mg Adalimumab Dosing Compared With 40 mg Adalimumab Every Other Week Dosing
Rheumatoid ArthritisUnlock trial analytics

Study Endpoints

Primary Endpoints

Reduction in DAS28
Week 24

The proportion of patients with improvement in arthritis (DAS 28) at week 24 -changes from screening in DAS 28 , HAQ, , CRP. ANOVA analysis and descriptive statistics. An interim evaluation of the above parameters will be performed at week 16 (visit 4) and yearly afterwards for 3 more years in those patients who will continue drug study during the extension period

O'Leary-Santa Interstitial Cystitis Symptom Index and Problem Index (OSPI) Score
Baseline/12 Weeks

Improvement in the O'Leary Sant Symptom and Problem Index from baseline to week 12 Total scores on a scale range: 0-36 (0, meaning no symptoms to 36, meaning the most severe symptoms)

Number of patients who achieve a DAS28 < 3.2
0, 1, 3, 6, 9, 12 and 24 months (DAS28)
Number of Participants Meeting the Assessment of Spondyloarthritis International Society (ASAS) ASAS20 Response Criteria
Week 12

ASAS20 responder had improvement of 20% or more and absolute improvement of at least 10 units (on a scale of 0 \[least\] to 100 \[worst\]) from Baseline in at least 3 of the following 4 domains, with absence of deterioration (change for worse of at least 20% and net worsening of at least 10 units) in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Bath Ankylosing Spondylitis Functional Index (BASFI); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores).

Change From Baseline in Modified Total Sharp X-Ray Score at Week 26
Baseline, Week 26

Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease. Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 \[no damage\] to 5 \[complete collapse or total destruction of joint\]) and for joint space narrowing (0 \[no damage\] to 4 \[complete luxation of joint\]). Scores were added, giving total mTSS (0 \[normal\] to 380 \[maximal disease\]). Large positive change in mTSS indicates disease progression; small positive/no change indicates slowing/halting of disease progression.

Number of Subjects Achieving Pediatric American College of Rheumatology 30% (PedACR30) Response at Week 16
Week 16

Response defined as at least 30% improvement in 3 or more of 6 juvenile rheumatoid arthritis (JRA) core set criteria, and at least 30% worsening in not more than 1 JRA criterion, compared with baseline. JRA core set criteria include physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion \[LOM\] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein.

Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12
Week 12

ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = at least 20% improvement (vs. baseline) and an absolute improvement ≥ 10 units on a 0 - 100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain.

Number of Participants Who Achieved a Physician's Global Assessment (PGA) of Clear (0) or Minimal (1) at Week 16
Week 16

The PGA is a 6-point scale used to measure the severity of a patient's disease. Plaque elevation, scaling, and erythema are rated from 0= clear (no plaque elevation; no scaling; erythema=hyperpigmentation, pigmented macules, diffuse faint pink or red coloration) to 5=very severe (plaque elevation=very marked; scaling=very coarse; erythema=very severe \[extreme red coloration, dusky to deep red coloration\]).

Frequency of Adverse Events
Up to 34 weeks (24 week study treatment plus 70-day follow-up period)

Serious adverse events were collected from the time of informed consent, and nonserious adverse events were collected from the time of first dose of adalimumab, until 70 days after the last injection of adalimumab. Refer to the Reported Adverse Events section of this results disclosure for specific adverse events reported. Note: Severe events considerably interfered in patients' usual activities and may have been life-threatening. Serious events were life-threatening; resulted in hospitalization, congenital anomalies, or disability; or required intervention to prevent seriousness.

Changes of Physical Examination
Baseline and 24 weeks

Physical examination findings were compared between Baseline and Week 24, and changes were recorded (Normal at Baseline to Abnormal at Week 24; or Abnormal at Baseline to Normal at Week 24). Physical examination criteria (normal vs. abnormal) were at the clinical judgement of the examining physician. Significant changes in physical examination from Baseline were considered to be adverse events.

Deviation From Normal Laboratory Ranges
24 weeks

Laboratory values were assessed for values above and below the normal (reference) ranges used by the central laboratory. Note abbreviations used in table: Alk. phosphatase = alkaline phosphatase, ALT = alanine aminotransferase, AST = aspartate aminotransferase, ESR = erythrocyte sedimentation rate

Vital Sign Values
24 weeks

Vital signs values were assessed for values above and below the normal (reference) ranges used by the central laboratory. Note, in table, BP = blood pressure.

The Number of Responders According to the American College of Rheumatology (ACR) 20 Response Criteria at Week 12 Involving the Comparison of Adalimumab 80 mg Monthly Dose Versus Placebo and Adalimumab 40 mg Every Other Week (Eow)
Week 12

Comparison of adalimumab 80 mg monthly dose versus placebo and adalimumab 40 mg eow in the number of responders with ACR criteria improvement consisting of 20%, (ACR20) reduction in tender or swollen joint counts (TJC or SJC, respectively) and 20% improvement in 3 of the following 5 criteria: \[1\] physician's global assessment of disease activity (PGA), \[2\] subject's assessment of disease activity, \[3\] subject's assessment of pain, \[4\] subject's assessment of physical disability via a health assessment questionnaire disability index(HAQ-DI), and \[5\] C-reactive protein (CRP) at each visit

Percentage of Participants Who Achieve a PASI75 Response at Week 16 Compared With Baseline (Week 0)
Week 0 and Week 16

PASI75 is defined as at least a 75% reduction in PASI (Psoriasis Area and Severity Index) score compared with the Baseline PASI score. PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. The percent decrease in score is calculated as (Week 0 PASI score minus Week 16 PASI score) divided by Week 0 PASI score. Positive percent decreases indicate improvement, with best improvement being 100%. The outcome measure is the percentage of participants who had at least a 75% PASI score decrease.

Number of Subjects With Psoriasis Area and Severity Index (PASI) 75 Response at 16 Weeks
16 weeks

PASI 75 is a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI). The PASI scale runs from 0-72, where 0 = no psoriasis and 72 = complete erythroderma of the severest possible degree

Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 26
Week 26

Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. The primary endpoint was clinical remission as defined by PCDAI score ≤ 10. The comparison was between High-Dose adalimumab versus Low-Dose adalimumab in the intent-to-treat population.

Mean Extent of Exposure - Duration in Days
Up to 24 weeks

Extent of exposure for all adalimumab treated subjects

Total Number of Injections of Adalimumab
Up to 24 weeks

Extent of exposure for all adalimumab treated subjects

Compliance With Number of Injections of Adalimumab. Compliance Corresponds to Patients Who Received Their Injections.
Up to 24 weeks

Treatment compliance (%) = 100 \* (Number of doses of study medication actually received)/(Number of doses planned during the subject's participation in the study).

Number of Participants in Clinical Remission at Treatment Week 20. Clinical Remission Defined as Harvey Bradshaw Index (HBI) Score Less Than 5.
Week 20 of treatment

5-items that assess general well-being, abdominal pain, diarrhea, abdominal mass, and complications. Score is total of 1) subject well-being (0=very well; 4=terrible); 2) abdominal pain (0=none; 3=severe); 3) diarrhea (number of time per day); 4) abdominal mass (0=none; 3=definite and tender); 5) complications (number). Maximum total score for HBI is not specified, is dependent on number of diarrhea times each day and number of complications. Clinical remission = HBI less than 5. Highest total score at Baseline was 47. Missing data were imputed using non-responder imputation (NRI).

Proportion of Participants With Clinical Remission Per Mayo Score at Week 8
Week 8

Clinical remission per Mayo score is defined as a total Mayo score \<= 2 and no individual subscore \> 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, Endoscopy Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).

Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 8
Week 8

Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: Stool Frequency Subscore (SFS), Rectal Bleeding Subscore (RBS), Endoscopy Subscore, and Physician's Global Assessment Subscore (PGA), each of which ranges from 0 (normal) to 3 (severe disease).

Proportion of Participants Who Achieved Clinical Remission Per Mayo Score at Week 52
Week 52

Clinical remission per Mayo score is defined as a total Mayo score of at least 2 and no individual subscore greater than 1. The Mayo Score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 12 (severe disease) and is a composite of 4 subscores: SFS, RBS, Endoscopy Subscore, and PGA, each of which ranges from 0 (normal) to 3 (severe disease).

Number of Subjects Without Mucosal Ulceration at Week 12
Week 12

Subjects were to have undergone up to 4 endoscopies to evaluate the presence or absence of mucosal ulceration: at Screening, at Week 12 (subjects who moved to open label (OL) drug between Week 8 and Week 12 because of disease flare or non-response were evaluated by endoscopy prior to receiving OL dosing), at the time of switch from blinded study drug to OL adalimumab at any time after Week 12, and at Week 52 or Early Termination. Subjects who remained blinded for the entire 52-week trial or switched to OL adalimumab between Week 8 and Week 12 were to have undergone 3 endoscopies.

AEs, laboratory data, physical examinations and vital signs
ACR20 response
Week 12
Number of Subjects With American College of Rheumatology (ACR) Criteria Improvement of at Least 20%, 50%, and 70% (ACR20/50/70 Responders, Respectively)
Every 4 weeks up to Week 24 and every 12 weeks thereafter until study completion or discontinuation (Final value)

Number of responders with ACR criteria improvement consisting of 20%, 50%, and 70% (ACR20, ACR50, and ACR70, respectively) reduction in tender or swollen joint counts (TJC or SJC, respectively) and 20%, 50%, and 70% improvement, respectively, in 3 of the following 5 criteria: \[1\] physician's global assessment of disease activity (PGA), \[2\] subject's assessment of disease activity, \[3\] subject's assessment of pain, \[4\] subject's assessment of physical disability via a health assessment questionnaire disability index(HAQ-DI), and \[5\] C-reactive protein (CRP) at each visit.

ASAS 20/40/50/70
ASAS 5/6
BASDAI score
Proportion of subjects achieving clinical response at Week 16 relative to the Baseline (Week 0) PASI score.
Week 16
Safety parameters
Every Study Visit
PsARC
ACR20
Physician Global Assessment for Psoriasis and Psoriasis Target Lesion Assessment
Patient reported outcomes
Proportion of subjects achieving clinical response at Week 16 relative to the Baseline (Week 0) PASI score
Week 16
Induction of clinical remission (CDAI score < 150 at Week 4)
Percentage of Subjects Achieving Clinical Remission
Week 156

Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of \< 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.

Number of Subjects With American College of Rheumatology (ACR) Criteria Improvement Consisting of 20%, 50%, and 70% (ACR20/50/70 Responders, Respectively)
Every 4 weeks up to Week 24 and every 12 weeks thereafter until Study completion or discontinuation (final value)

Number of responders with ACR criteria improvement consisting of 20%, 50%, and 70% (ACR20/50/70, respectively) reduction in tender or swollen joint counts (TJC or SJC, respectively) and 20%, 50%, and 70% improvement, respectively, in 3 of the following 5 criteria: 1) physician's global assessment of disease activity (PGA), 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire (DI-HAQ), and 5) C-reactive protein (CRP) at each visit.

Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R
Week 16 of Period R

The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.

Number of Responders With a Reduction of Signs and Symptoms of Ankylosing Spondylitis (AS) as Measured With ASAS International Working Group Response Criteria (ASAS 20).
Week 12

ASAS 20 responders - improvement of \>=20% and absolute improvement of \>=10 units from Baseline in a visual analog scale (VAS) for \>=3 of 4 domains; Patient's Global Assessment of disease activity VAS (0 \[none\]-100 \[severe\]), Total Back Pain VAS (0 \[no pain\]-100 \[severe\]), BASFI VAS (0 \[easy\]-100\[impossible\]); and Inflammation VAS (0 \[none\]-10 \[very severe\]) and absence of deterioration in the potential remaining domain, defined as a worsening of \>=20% and a net worsening of \>=10 units. Applied to each scale and not to an overall global scale.

Mean Change in the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) Compared Against a Historical Control Group (Outcomes in Ankylosing Spondylitis International Study [OASIS]) Using the ANCOVA Model Adjusting for Baseline mSASSS Score
Week 104

Radiographic progression was based on change in mSASSS scoring (comparison of the means) from double-blind Baseline visit to Week 104. The mSASSS is the sum of the lumbar and cervical spine score ( 0 \[no change\] to 72 \[progression\]), derived from scoring the anterior site of the lumbar spine (T12 to S1) and the cervical spine (C2 to T1) as either 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), 3 (bridging syndesmophyte), or N (vertebral body not evaluable). Data from NCT00195819 was compared with data from AS patients in OASIS.

Number of Subjects With a Reduction in Signs and Symptoms as Measured by Assessments of Ankylosing Spondylitis (ASAS) 20 Response at Week 12
Week 12

ASAS 20 responders - improvement of \>=20% and absolute improvement of \>=10 units from Baseline in a visual analog scale (VAS) 0 \[no disease activity\]-100 \[high disease activity\]) for \>=3 of 4 domains; Patient's Global Assessment of disease activity VAS; (0\[none\]-100 \[severe\]), Total Back Pain VAS; (0 \[no pain\]-100 \[severe\]), BAth Ankylosing Spondylitis Functional Index (BASFI) VAS (0 \[easy \]-100\[impossible\]); and Inflammation VAS; (1 \[no pain\] to 10 \[severe pain\]) and absence of deterioration in the potential remaining domain. Applied to each scale and not to an overall global scale.

QOL
12 months
Clinical remission (CDAI<150).
56 weeks
Adverse Events
Throughout the Study
Job loss measurement
Change of disease activity score (DAS28) compared with study entry
Week 12
EULAR and ACR response criteria at week 12
Week 12
Change in disease activity score at visit week 12 as compared to baseline
Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 520
Week 520

ACR20 response criteria were: \>=20% improvement in tender joint count; \>=20% improvement in swollen joint count; and \>=20% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.

Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260
Week 260

ACR20 response criteria were: \>=20% improvement in tender joint count; \>=20% improvement in swollen joint count; and \>=20% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.

Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 520
Week 520

ACR50 response criteria were: \>=50% improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.

Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 260
Week 260

ACR50 response criteria were: \>=50% improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.

Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 520
Week 520

ACR70 response criteria were: \>=70% improvement in tender joint count; \>=70% improvement in swollen joint count; and \>=70% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.

Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 260
Week 260

ACR70 response criteria were: \>=70% improvement in tender joint count; \>=70% improvement in swollen joint count; and \>=70% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.

Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 520
Week 520

Clinical remission on modified Disease Activity Score (DAS28) was a value \<2.6; \>=2.6 to \<=3.2 indicated low disease activity; \>3.2 to \<=5.1 indicated moderate disease activity; and \>5.1 indicated high disease activity. DAS28 score is calculated using the number of tender joints and swollen joints (out of 28 each), patient global assessment of disease activity, and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response).

Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 260
Week 260

Clinical remission on modified Disease Activity Score (DAS28) was a value \<2.6; \>=2.6 to \<=3.2 indicated low disease activity; \>3.2 to \<=5.1 indicated moderate disease activity; and \>5.1 indicated high disease activity. DAS28 score is calculated using the number of tender joints and swollen joints (out of 28 each), patient global assessment of disease activity, and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response).

Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 520
Baseline of prior Phase 1, 2, or 3 adalimumab study and Week 520

The HAQ-DI is a measure of disability that ranges from 0 to 3. Decrease in score indicates improvement in physical function; a decrease of 0.22 or greater from Baseline score is clinically significant. Participants assessed their ability to perform at least 6 of the following 8 specific tasks (1. dress/groom; 2. arise; 3. eat; 4. walk; 5. reach; 6. grip; 7. maintain hygiene; 8. maintain daily activity) over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The 8 task scores are added and the sum is divided by the number of tasks assessed (range = 6 to 8). This yields a HAQ-DI score of 0 to 3.

Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 260
Baseline of prior Phase 1, 2, or 3 adalimumab study and Week 260

The HAQ-DI is a measure of disability that ranges from 0 to 3. Decrease in score indicates improvement in physical function; a decrease of 0.22 or greater from Baseline score is clinically significant. Participants assessed their ability to perform at least 6 of the following 8 specific tasks (1. dress/groom; 2. arise; 3. eat; 4. walk; 5. reach; 6. grip; 7. maintain hygiene; 8. maintain daily activity) over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The 8 task scores are added and the sum is divided by the number of tasks assessed (range = 6 to 8). This yields a HAQ-DI score of 0 to 3.

Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 24
Week 24

Patients were responders if they had: \>= 20% improvement in tender joint count; \>= 20% improvement in swollen joint count; and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.

Change From Baseline in Modified Total Sharp X-ray Score at Week 52
Baseline and Week 52

Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 52. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 \[normal\] to 398 \[maximal disease\]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.

Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 52
Baseline and Week 52

Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from baseline in the disability index of the HAQ indicated improvement.

Patients in remission at 24 weeks.
24 weeks

Number in remission at 24 weeks (absence of clinical-evidence synovitis (no tender/swollen joints) \& CRP\< 5mg/ml)

The proportion of subjects who are Responders, achieving at least Moderate Improvement on the Physician's Global Assessment, after 12 weeks of treatment during Period A (double-blind phase).
at completion of double-blind phase (12 weeks)
Percentage of Participants Achieving Clinical Response at Week 16
Baseline, Week 16

Clinical response is defined as a Physician's Global Assessment (PGA) of clear, minimal, or mild (scores of 0, 1, or 2) with a minimum of 2 grades improvement (reduction) from baseline. PGA is a physician's assessment of the severity of disease based on a 6-point scale (score of 0 = clear and 5 = very severe).

Number of Participants With American College of Rheumatology (ACR)20 at Week 12 of the Double-Blind Period
Week 12

American College of Rheumatology (ACR) criteria improvement consisting of 20% (ACR20) reduction in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. Week 12 = end of Double-Blind period.

Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment
Week 52 of double-blind treatment

Clinical remission=Crohn's Disease (CD) Activity Index (CDAI) \<150; number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI total score is \>= 0 and without upper limit. Low score=less severe CD activity. Decrease indicates improvement.

The Number of Subjects With a Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) at Week 4
4 Weeks

CDAI is used to quantify the symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score above 450 indicates severe disease. Comparison of the number of subjects with a clinical remission (CDAI \< 150) in the adalimumab 160 mg (Week 0)/ 80 mg (Week 2) and adalimumab 80 mg (Week 0)/ 40 mg (Week 2) groups at Week 4.

Number of Participants With a 50% Reduction in PASI (Psoriasis Area and Severity Index) Score Compared With Baseline PASI Score (PASI50 Response)
Baseline and 12, 24, 36, 52, 76, 100, 160, and 208 weeks after the first dose of adalimumab

PASI scores range from 0 (best outcome) to 72 (worst outcome including erythema, induration, desquamation, and area affected). Baseline is defined as the last available PASI value prior to the first dose of study drug (adalimumab or placebo) in Study M04-688 (NCT00338754).

Psoriasis Area and Severity Index
Week 12
Number of Responders With American College of Rheumatology (ACR) Criteria Improvement of at Least 20%, 50%, and 70% (ACR 20/50/70 Responders)
Every 6 weeks up to Week 24 and every 12 weeks thereafter up to study completion or discontinuation (final value)

Number of subjects with American College of Rheumatology (ACR) criteria improvement consisting of 20%, 50%, and 70% (ACR20, ACR50, and ACR70, respectively) reduction in tender or swollen joint counts \[TJC or SJC, respectively\] and 20%, 50%, and 70% improvement, respectively, in 3 of the following 5 criteria: \[1\] physician's global assessment of disease activity \[PGA\], \[2\] subject's assessment of disease activity, \[3\] subject's assessment of pain, \[4\] subject's assessment of functional disability via a health assessment questionnaire \[HAQ\], and \[5\] C-reactive protein \[CRP\]) at each visit

Sharp Score
Week 24
comparison of the induction of clinical remission
(achievement of a CDAI <150) of adalimumab 40 mg and 80 mg vs. placebo at Week 4.

Secondary Endpoints

Interstitial Cystitis Symptom Index (ICSI)
Baseline/ 12 weeks
Interstitial Cystitis Problem Index (ICPI)
Baseline/12 Weeks
Pelvic Pain Urgency/Frequency (PUF) Score
Baseline12 Weeks
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Adalimumab, Behcet with arthritisEXPERIMENTAL -
adalimumabEXPERIMENTALAdalimumab 80mg subcutaneous loading dose followed by 40 mg subcutaneous every 2 weeks for 12 weeks
Inactive drugPLACEBO_COMPARATORPlacebo in identical syringe subcutaneous every 2 weeks for 12 weeks
methotrexate + adalimumabEXPERIMENTALMethotrexate and intraarticular triamcinolone hexacetonide plus adalimumab.
methotrexate + placeboPLACEBO_COMPARATORMethotrexate and intraarticular triamcinolone hexacetonide and placebo
PlaceboPLACEBO_COMPARATORBlinded placebo from Week 0 to Week 10, open-label adalimumab from Week 12 to Week 24.
DB PlaceboPLACEBO_COMPARATORParticipants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
DB adalimumabEXPERIMENTALParticipants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
DB Adalimumab/OL AdalimumabEXPERIMENTALParticipants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
DB Placebo/OL AdalimumabEXPERIMENTALParticipants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
DB Adalimumab/RE OL AdalimumabEXPERIMENTALParticipants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible at Week 12 or after) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
DB Placebo/RE OL AdalimumabEXPERIMENTALParticipants received double-blind placebo administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible at Week 12 or after) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Open LabelEXPERIMENTAL -
40 mgACTIVE_COMPARATOR40 mg every other week
80 mgACTIVE_COMPARATOR80 mg monthly
adalimumab + placeboACTIVE_COMPARATORadalimumab + placebo (vehicle ointment)
adalimumab + calcipotriol/betamethasoneACTIVE_COMPARATORadalimumab + calcipotriol/betamethasone ointment
1EXPERIMENTAL -
Open-label adalimumab (Week 0 to Week 4)ACTIVE_COMPARATORAll subjects received an open-label adalimumab induction regimen. Subjects weighing greater than or equal to 40 kg at Baseline received 160 mg at Week 0 and 80 mg at Week 2. Subjects weighing less than 40 kg at Baseline received 80 mg at Week 0 and 40mg at Week 2.
Low-Dose Adalimumab: 20 mg or 10 mg eow (Week 4 to Week 52)ACTIVE_COMPARATORSubjects randomized to the Low-Dose treatment group received either 20 mg adalimumab every other week (eow) (if Week 4 body weight \[BW\] was greater than or equal to 40 kg) or 10 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blind (DB) ew therapy they could be switched to open-label ew therapy.
High-Dose Adalimumab: 40 mg or 20 mg eow (Week 4 to Week 52)ACTIVE_COMPARATORSubjects randomized to the High-Dose treatment group received either 40 mg adalimumab every other week (eow) (if Week 4 body weight \[BW\] was greater than or equal to 40 kg) or 20 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blinded (DB) ew therapy they could be switched to open-label ew therapy.
Adalimumab 80/40EXPERIMENTAL -
Adalimumab 160/80/40EXPERIMENTAL -
adalimumab groupEXPERIMENTAL -
placebo groupEXPERIMENTAL -
Double BlindPLACEBO_COMPARATORBlinded study through Week 52. Adalimumab compared to placebo during blinded portion.
AACTIVE_COMPARATOR -
BACTIVE_COMPARATOR -
CPLACEBO_COMPARATOR -
Adalimumab 40 mg every other week (eow)EXPERIMENTAL -
DB adalimumab 20 mg ewEXPERIMENTALSubjects received 20 mg adalimumab subcutaneously (SC) once weekly (ew) and concomitant methotrexate (MTX) during the double-blind (DB) phase.
DB adalimumab 40 mg eowEXPERIMENTALSubjects received 40 mg adalimumab subcutaneously (SC) every other week (eow) and concomitant methotrexate (MTX) during the double-blind (DB) phase. Subjects received placebo injections SC and concomitant MTX on the alternate weeks during the DB phase.
DB placebo ewPLACEBO_COMPARATORSubjects received placebo subcutaneously (SC) once weekly (ew) and concomitant methotrexate (MTX) during the double-blind (DB) phase.
DB adalimumab 20 mg ew/OL adalimumab 40 mg eowEXPERIMENTALSubjects received adalimumab 20 mg subcutaneously (SC) once weekly (ew) during the double-blind (DB) phase, then adalimumab 40 mg SC every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
DB adalimumab 40 mg eow/OL adalimumab 40 mg eowEXPERIMENTALSubjects received adalimumab 40 mg subcutaneously (SC) every other week (eow) with placebo on alternate weeks during the double-blind (DB) phase, then adalimumab 40 mg SC eow during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
DB placebo ew/OL adalimumab 40 mg eowEXPERIMENTALSubjects received placebo subcutaneously (SC) once weekly (ew) during the double-blind phase, then adalimumab 40 mg SC every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
TNF-antagonistEXPERIMENTALAdalimumab, 40 mg, 2-weekly Methotrexate, rapid escalation to 25mg, weekly Folic Acid 5mg, 6 days a week
Placebo + MTXACTIVE_COMPARATORPlacebo, 2 weekly Methotrexate, rapid escalation to 25mg, weekly Folic Acid 5mg, 6 days a week
Adalimumab 40 mg qwkEXPERIMENTALInitial dose of adalimumab 160 mg at Week 0, adalimumab 80 mg at Week 2, followed by 40 mg weekly (qwk) starting at Week 4 through Week 15.
Adalimumab 40 mg eowEXPERIMENTALInitial dose of adalimumab 80 mg at Week 0, followed by adalimumab 40 mg eow (every other week) starting at Week 1 through Week 15.
Adalimumab 80 mgEXPERIMENTALAdalimumab 80 mg administered subcutaneously every other week
Adalimumab 40 mgEXPERIMENTALAdalimumab 40 mg administered subcutaneously every other week
Placebo eowPLACEBO_COMPARATORSubjects received placebo subcutaneously (SC) every other week (eow) during the double-blind treatment period lasting 52 weeks.
OL Adalimumab 40 mg eowEXPERIMENTALSubjects received open-label (OL) 40 mg adalimumab subcutaneously (SC) every other week (eow) during the double-blind treatment period lasting 52 weeks.
Adalimumab 160 mg/80 mgEXPERIMENTAL -
Adalimumab 80 mg/40 mgEXPERIMENTAL -
Adalimumab 40 mg every other weekEXPERIMENTAL -
Adalimumab 80 mg every other weekEXPERIMENTAL -
20 mgEXPERIMENTAL20 mg adalimumab eow

Interventions

NameTypeDescription
Adalimumab (Humira)DRUGOpen label pilot trial. The study includes 3 phases : 1. Open label treatment period of 24 weeks. 2. Extension follow -up (3 years): Patients who responded well to study drug and their disease relapsed within the first 12 weeks following study drug interruption will be eligible to receive the study drug for 3 years in order to comply with the Israeli Ministry of Health requirements. 3. Safety follow-up: For patients who withdraw from either the open label treatment period or extension period, for another 24 weeks.
AdalimumabDRUG80 mg loading dose given subcutaneously followed by 40 mg dose given subcutaneously every two weeks over a twelve week period
inactive drugOTHER80 mg loading dose given subcutaneously followed by 40 mg dose given subcutaneously every two weeks over a twelve week period
PlaceboDRUGSaline injection 0.9%, 0.8 ml s.c. every second week up to 2 years
Double-blind adalimumabBIOLOGICALDouble-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)
Double-blind PlaceboDRUGDouble-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow)
Open-label AdalimumabBIOLOGICALOpen-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Open-labelAdalimumabRescueBIOLOGICALOpen-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) as rescue treatment to complete the first 26 weeks in the study- dependent on participant eligibility (increase in disease activity), applies to Weeks 12 to 26
Calcipotriol/Betamethasone OintmentDRUGTopical ointment (calcipotriol 50 mcg/g and betamethasone 500 mcg/g) to be applied once daily to affected psoriasis skin on trunk and extremities for first 4 weeks and as needed from Week 5 through Week 16
placebo (vehicle ointment)DRUGTopical vehicle ointment (matching active calcipotriol/betamethasone ointment) to be applied once daily to affected psoriasis skin on trunk and extremities for first 4 weeks and as needed from Week 5 through Week 16
Humira (adalimumab)BIOLOGICALStudy drug will be provided as a sterile, preservative-free solution for subcutaneous injection, contained in a pre-filled syringe housed in a pen device (pre-filled pen). Loading dose of 80 mg of adalimumab subcutaneously (sc) at Baseline, and 40 mg of adalimumab sc at Week 1, followed by 40 mg of adalimumab sc every other week (eow) for 24 weeks.
MTXDRUGMTX 7.5 to 25 mg once weekly
placebo adalimumab, placebo MTXDRUGplacebo injections once every other week after 2 injections at Baseline (adalimumab) placebo capsules once weekly (MTX)
adalimumab (D2E7)BIOLOGICALAdalimumab 40 mg every other week, subcutaneous
MethotrexateDRUG -
placebo for adalimumabDRUGplacebo eow Week 0 - Week 12
Folic AcidDRUG -
Adalimumab 80 mgBIOLOGICALAdalimumab 80 mg administered subcutaneously (SC) every other week (eow) for 12 weeks, followed by adalimumab 40 mg SC eow for 92 weeks.
Adalimumab 40 mgBIOLOGICALAdalimumab 40 mg administered subcutaneously every other week for 104 weeks
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Eligibility Criteria

Age Range18 Years to 80 Years
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: 1. Able and willing to give written informed consent and comply with the requirements of the study protocol. 2. Patients with Behcet disease ,who fulfilled the International Study group criteria for Behcet Disease. 3. Experienced an inadequate response to previous or current tre...

Countries:IsraelUnited StatesDenmarkChinaJapanCanadaRussiaAustraliaGermanyPuerto RicoUnited KingdomAustriaBelgiumCzechiaFinlandFranceGreeceItalyNetherlandsSpainSwedenSwitzerlandTurkey (Türkiye)PolandIrelandNorwayPortugalSlovakiaHungaryArgentinaNew ZealandSouth AfricaTaiwan
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Frequently asked questions about Adalimumab

What is Humira used for in psoriasis?

Humira is a monoclonal antibody used for the treatment of psoriasis. It is being developed by Abbott Laboratories for this dermatological condition. In clinical trials, Humira has been studied as an add-on therapy for patients with psoriasis who have had an inadequate response to their current treatment.

What does Humira target?

Humira is a monoclonal antibody that targets tumor necrosis factor-alpha (TNF-alpha). By binding to TNF-alpha, Humira is designed to block its activity, which is involved in the inflammatory process of psoriasis. This mechanism is intended to reduce the signs and symptoms of the condition.

Who makes Humira?

Humira is developed by Abbott Laboratories, a company traded under the ticker symbol ABT. The company is conducting clinical research on Humira for the treatment of psoriasis, with a completed Phase 3 trial evaluating its use in this indication.

What phase is Humira in for psoriasis?

Humira is in Phase 3 clinical development for the treatment of psoriasis. A Phase 3 trial, identified as NCT00513370, has been completed. This trial was an open-label, uncontrolled study that enrolled 203 participants in Canada. Humira is still considered investigational for this use.

What clinical trials is Humira in for psoriasis?

Humira has one completed clinical trial for psoriasis, registered as NCT00513370. This Phase 3 study was titled "A Canadian Open-Label Access Program to Evaluate Adalimumab When Added to Inadequate Therapy for the Treatment of Psoriasis." The trial enrolled 203 adults aged 18 years and older in Canada.

Is Humira the same as adalimumab?

Yes, Humira is the same as adalimumab. The clinical trial for Humira in psoriasis, NCT00513370, specifically evaluates adalimumab, which is the scientific name for Humira. This alternative name is used in the trial title and is important for identifying the drug in medical literature.