Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AIN457 · 23 trials · 18 indications
Assessed the efficacy of secukinumab relative to placebo at week 16 using Non-responder imputation (NRI) and based on the percentage of participants achieving an ACR20 response (ACR = American College of Rheumatology). ACR20 response criteria is response ≥ 20% improvement based on: Swollen Joint Count (SJC)/Tender Joint Count (TJC), Patient's global assessment of disease activity (PaGA) (Visual Analog Scale (VAS)), Physician's global assessment of disease activity (PhGA) (VAS), Patient's assessment of PsA pain intensity (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI), and High-sensitivity C-reactive protein (hsCRP) or Erythrocyte sedimentation rate (ESR).
Percentage of participants with active psoriatic arthritis (PsA) who achieved an American College of Rheumatology 50 (ACR50) response The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[most often Health Assessment Questionnaire (HAQ)\], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP)
The spinal pain numerical rating scale (NRS) is an 11-point scale to assess pain intensity in patients who are able to self-report. It is an 11-point scale from 0-10: 1) "0" = no pain. 2) "10" = the most intense pain imaginable. To calculate the average spinal pain, the patient was asked to answer 2 questions to get 2 pain ratings, the total spinal pain corresponding to the intensity of spinal pain experienced on an average over 24 hours during the previous week and the nocturnal back pain corresponding to the intensity of spinal pain experienced on an average over the night during the previous week.
Mixed model repeated measures (MMRM) analysis of change in Global OMERACT-EULAR Synovitis Score (GLOESS) score at Week 12 (observed data) to compare treatments The range for the GLOESS score is 0 to 144. GLOESS is the ultrasound scoring system measured for 24 pairs of joints. The scoring is from 0 to 3 for each joint; so the minimum score can be 0 and maximum can be 144.
Psoriasis Area and Severity Index (PASI) is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 90 responders were defined as participants achieving ≥ 90% improvement at Week 16
Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC)
ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire \[HAQ-DI\] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR20 response results at week 24 used non-responder imputation.
PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section(head: 0.1, arms: 0.2 body: 0.3 legs: 0.4)
Safety outcomes will be described in Adverse events section as there was not an efficacy primary outcome
Safety was assessed by frequency of adverse events including serious adverse events.
PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).
Combined unique active lesions (CUAL) observed on brain MRI scans performed every 4th week from week 4 to week 24 in patients with relapsing-remitting multiple sclerosis (RRMS). CUAL is defined as: new gadolinium (Gd)-enhancing lesions on T1-weighted, or new or enlarging lesions on T2-weighted MRI scans, without double counting.
Number (%) of patients achieving PASI 50, PASI 75, PASI 90, by visit and induction treatment
A participant was considered to be a responder according to the ACR20, 50 or 70 criteria if the participant had at least 20% 50% or 70% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)
Psoriatic Arthritis Response Criteria (PsARC) includes measures of tender and swollen joint counts, patient's assessment of pain, physician's and patient's global assessment of disease activity A subject is defined as a PsARC responder if, and only if, they have an improvement in two of the following four factors (with at least one factor being a joint count) and no worsening in the remaining factors: 1) Patient global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 2) Physician global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 3) Tender 78-joint count (improvement defined as decrease of at least 30%) 4) Swollen 76-joint count (improvement defined as decrease of at least 30%)
Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of 20% or more and absolute improvement of at least 1 units (on a scale of 0 \[least\] to 10 \[worst\]) from Baseline in at least 3 of the following 4 domains, with absence of deterioration (worsening of at least 20% an absolute Worsening of at least 1 unit) in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores
ASAS20 as described in Primary Outcome. ASAS40 responder had improvement of 40% or more and absolute improvement of at least 2 units (on a scale of 0 \[least\] to 10 \[worst\]) from Baseline in at least 3 of the following 4 domains, with no deterioration in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores). ASAS 5/6 responder had improvement of 20% or more) from Baseline in at least 5 of the following 6 domains: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (BASFI); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] scores); Spinal Mobility (BASFI); Acute phase reactant (CRP)
PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).
This outcome measure shows the proportion of participants in each of the AIN457 treatment groups who were relapse free throughout the study up to and including week 56.
AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
The PASI assessed the extent of psoriasis on four body surface areas (head, trunk and upper limbs) and the degree of plaque erythema, scaling and thickness. The PASI score accounted for the extent of body surface area affected by the erythema, scaling and thickness and the severity of these measures. The score ranged from 0 (no disease) to 72 (maximal disease) where a reduction in PASI score from baseline indicates improvement. The percentage change was calculated by subtracting the week 4 values from the baseline values.The percentage change was calculated for each entire treatment group (not for each participant). A positive percentage change from baseline indicates improvement.
The IGA is an instrument which captured and categorized the global assessment of all clinical signs and symptoms of disease. The investigator used all available information for the assessment, including subjective information from the participant and (where available) photographs taken at baseline. The IGA categories were clear, almost clear, mild disease, moderate disease, severe disease and very severe disease. This outcome measure shows the percentage of patients who experienced a category change from baseline. Category changes of 1, 2 or 3 indicate improvement.
Clinical response to treatment was assessed according to ACR20 criteria. A participant was defined as an ACR20 responder if the following 3 conditions were met: 1) ≥20% improvement in the number of tender joints, 2) ≥20% improvement in the number of swollen joint and 3) ≥20% improvement in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99 and 113.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
| Arm | Type | Description |
|---|---|---|
| Arm 1 | EXPERIMENTAL | Participants received 150 mg dose (dose level 1) of Secukinumab |
| Arm 2 | PLACEBO_COMPARATOR | Participants received Placebo of the study drug. |
| Arm 3 | ACTIVE_COMPARATOR | Participants who received Placebo and switched to dose level 1 (150 mg) of secukinumab. |
| Arm 4 | ACTIVE_COMPARATOR | Participants who received Placebo and switched to dose level 2 (300 mg) of secukinumab. |
| AIN457 6 mg/kg - 3 mg/kg i.v. | EXPERIMENTAL | AIN457 6 mg/kg i.v. infusion at baseline, followed by AIN457 3 mg/kg i.v. infusion every 4 weeks starting at Week 4 through Week 48 (exposure through Week 52). |
| Placebo | PLACEBO_COMPARATOR | Matching placebo from baseline to Week 16 and switch to AIN457 3mg/kg i.v. infusion every 4 weeks through Week 48 (exposure through Week 52). |
| Secukinumab 150 mg (Group A) | EXPERIMENTAL | Treatment Period 1: Secukinumab 150 mg (1 x 1.0 mL) s.c. administered at Baseline, Week 1, 2, 3 and 4 |
| Placebo (Group B) | PLACEBO_COMPARATOR | Treatment Period 1: Placebo (1 x 1.0 mL) s.c. administered at Baseline and Week 1, 2, 3 and 4 |
| Arm A1 | ACTIVE_COMPARATOR | Treatment Period 2: Secukinumab 150 mg (1 x 1.0 mL) plus placebo (1 x 1.0 mL) administered at Week 8, 12, 16 and 20 |
| Arm A2 | ACTIVE_COMPARATOR | Treatment Period 2: Secukinumab 150 mg (1 x 1.0 mL) plus placebo (1 x 1.0 mL) administered at Week 8, 12, 16 and 20 |
| Arm A3 | ACTIVE_COMPARATOR | Treatment Period 2: Secukinumab 300 mg (2 x 1.0 mL) administered at Week 8, 12, 16, and 20 |
| Arm B1 | ACTIVE_COMPARATOR | Treatment Period 2: Secukinumab 150 mg (1 x 1.0 mL) plus placebo (1 x 1.0 mL) administered at Week 8, 12, 16 and 20 |
| Arm B2 | ACTIVE_COMPARATOR | Treatment Period 2: Secukinumab 300 mg (2 x 1.0 mL) administered at Week 8, 12, 16, and 20 |
| Group 1 | ACTIVE_COMPARATOR | In Treatment Period-1: Patients in this group were administered secukinumab with 12 weeks of treatment from baseline. In Treatment Period-2: Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24 In Treatment Period 3 (extension period): the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52 |
| Group 2 | PLACEBO_COMPARATOR | In Treatment Period-1: Patients received placebo at baseline and same time points as secukinumab until Week 8. In Treatment Period-2: Patients commenced open-label secukinumab every 4 weeks from Week 12, as follows, based on their clinical characteristics at Week 12 In Treatment Period-3: Open-label secukinumab continued to be assigned to patients |
| AIN457 300 mg | EXPERIMENTAL | patients received AIN457 (secukinumab) 300 mg (two secukinumab 150 mg injections) s.c. (subcutaneously) once every week at weeks 0, 1,2,3, followed by monthly dosing starting at week 4 to week 48 inclusive |
| Ustekinumab | ACTIVE_COMPARATOR | patients received ustekinumab 45/90 mg (weight depended, according to label) s.c. (subcutaneously) and/or placebo secukinumab injections once every week at weeks 0,1,2, and 3 followed by monthly dosing starting at week 4 to week 48 inclusive |
| AIN457 150 mg - Fixed Interval (FI) | EXPERIMENTAL | 1 s.c. Secukinumab 150 mg Pre-filled seringue (PFS) injection + 1 s.c. Placebo (PBO) Secukinumab PFS injection every 4 weeks |
| AIN457 150 mg - Start of relapse (SoR) | EXPERIMENTAL | Start of relapse: 1 s.c. Secukinumab 150 mg PFS injection + 1 s.c. PBO Secukinumab PFS injection every 4 weeks Otherwise: 2 s.c. PBO Secukinumab PFS injections every 4 weeks |
| AIN457 300 mg - Fixed Interval (FI) | EXPERIMENTAL | 2 s.c. Secukinumab 150 mg PFS injections every 4 weeks |
| AIN457 300 mg - Start of Relapse (SoR) | EXPERIMENTAL | Start of relapse: 2 s.c. Secukinumab 150 mg PFS injection every 4 weeks Otherwise: 2 s.c. PBO Secukinumab PFS injections every 4 weeks |
| AIN457 300 mg - Open Label (OL) | EXPERIMENTAL | Open Label - Secukinumab 300mg every 4 weeks |
| AIN457 10mg/kg - 75 mg | EXPERIMENTAL | Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks |
| AIN457 10mg/kg - 150 mg | EXPERIMENTAL | Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks |
| Abatacept | ACTIVE_COMPARATOR | Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period). |
| AIN457150 mg- Induction period Only(IPO) | EXPERIMENTAL | secukinumab 150 mg (1 injection per dose) and placebo to secukinumab 150 mg (1 injection per dose). Induction period only (IPO) |
| AIN457 300 mg - IPO | EXPERIMENTAL | secukinumab- 2 x 150mg injections per dose |
| AIN457 300 mg FI | EXPERIMENTAL | 2 s.c. secukinumab 150 mg injections |
| AIN457 150 mg- Start of relapse (SoR) | EXPERIMENTAL | 1 s.c. secukinumab 150 mg injection + 1 s.c. PBO secukinumab injection |
| AIN457 300 mg- SoR | EXPERIMENTAL | 2 s.c. secukinumab 150 mg injections |
| AIN457C 300 mg every 2 week dosage regimen | EXPERIMENTAL | AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each. every 2 weeks |
| AIN457C 300 mg monthly dosage regimen | EXPERIMENTAL | AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg e |
| AIN 457 Core | EXPERIMENTAL | (10mg/kg i.v.). AIN 457 core study /AIN 457 Extension |
| AIN457 Placebo Core | EXPERIMENTAL | (10mg/kg i.v.). AIN 457 placebo core study /AIN 457 Extension |
| Fixed-time interval regimen | EXPERIMENTAL | Secukinumab 150 mg subcutaneous (sc) administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter |
| Treatment at start of relapse regimen | EXPERIMENTAL | Placebo administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter. If relapse, then switch to secukinumab 150 mg sc administered every 4 weeks |
| Open-label | EXPERIMENTAL | Secukinumab 150 mg sc administered every 4 weeks |
| AIN457 1x25mg | EXPERIMENTAL | - |
| AIN457 3x25mg | EXPERIMENTAL | - |
| AIN457 3x75mg | EXPERIMENTAL | - |
| AIN457 3x150mg | EXPERIMENTAL | - |
| AIN457 | EXPERIMENTAL | - |
| Induction Single Dose | EXPERIMENTAL | Induction with single injection - "Single": secukinumab (AIN457) 150 mg s.c. administered at Week 1, Baseline through Week 12 |
| Induction Monthly Dose | EXPERIMENTAL | Induction with monthly injections - "Monthly": secukinumab (AIN457) 150 mg s.c. administered at weeks 1, 5, 9, Baseline through Week 12 |
| Induction Early Loading Dose | EXPERIMENTAL | Early loading induction - "Early": secukinumab (AIN457) 150 mg s.c. administered at weeks 1, 2, 3, 5, Baseline through Week 12 |
| Placebo Dose | PLACEBO_COMPARATOR | Placebo administered at weeks 1, 2, 3, 5, 9, Baseline through Week 12 |
| AIN457 (2x 10mg/kg) | EXPERIMENTAL | Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22. |
| Part 1 - AIN457A 10 mg/kg | EXPERIMENTAL | AIN457A 10.0 mg/kg was administered intravenously as a single dose. |
| Part 1 - Placebo | PLACEBO_COMPARATOR | Placebo to AIN457A was administered intravenously as a single dose |
| Parts 1 and 2 - AIN457A 1.0 mg/kg | EXPERIMENTAL | AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| Part 1 and 2 - AIN457 0.1 mg/kg | EXPERIMENTAL | AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| Part 1 and 2 - AIN457 10 mg/kg | EXPERIMENTAL | AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| AIN457 3 mg/kg | EXPERIMENTAL | Participants randomized to this arm received AIN457 3 mg/kg on day 1, and then matching placebo on days 15 and 29. |
| AIN457 10 mg/kg | EXPERIMENTAL | Participants randomized to this arm received AIN457 10 mg/kg on day 1, and then matching placebo on days 15 and 29. |
| AIN457 10 mg/kg x3 | EXPERIMENTAL | Participants randomized to this arm received AIN457 3 mg/kg on days 1, 15 and 29. |
| AIN457 0.3 mg/kg | EXPERIMENTAL | Participants received AIN457 0.3 mg/kg IV on Day 1. |
| AIN457 1.0 mg/kg | EXPERIMENTAL | Participants received AIN457 1.0 mg/kg IV on Day 1. |
| AIN457 3.0 mg/kg | EXPERIMENTAL | Participants received AIN457 3.0 mg/kg IV on Day 1. |
| Cohort 1 | EXPERIMENTAL | Participants were administered with AIN457 (Sp2/0derived) 10 milligrams per kilogram (mg/kg) intravenous (i.v.) dose on Day 1 and Day 22. |
| Cohort 2 | EXPERIMENTAL | Participants were administered with AIN457 (Sp2/0 or Chinese hamster ovary cell (CHO) derived) 10 mg/kg, (CHO derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and if needed a second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. 3 participants from cohort 1 rolled on into this cohort. |
| Cohort 3 | EXPERIMENTAL | Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22. |
| Cohort 4 | EXPERIMENTAL | Extension period: Participants were administered with AIN457 10 mg/kg, i.v. (with or without a short course of corticosteroids) once a flare had occurred, or periodically at a frequency of not more than once per month at the discretion of the investigator. |
| Cohort 5 | EXPERIMENTAL | Participants were administered with AIN457 30 mg/kg single i.v. dose. A second dose was given when all 4 participants completed at least 29 days, and the 30 mg/kg dose was well tolerated by all. |
| Cohort 6 Arm 1 | EXPERIMENTAL | Participants were administered with AIN457 300 mg subcutaneously (s.c.) and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43). |
| Cohort 6 Arm 2 | EXPERIMENTAL | Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43). |
| Cohort 6 Arm 3 | EXPERIMENTAL | Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every 4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15 and 43 to maintain masking of treatment groups. |
| Secukinumab | EXPERIMENTAL | Secukinumab over 24 weeks |
| oral corticosteroid | ACTIVE_COMPARATOR | - |
| Part 1 - AIN457A 0.3 mg/kg | EXPERIMENTAL | AIN457A 0.3 mg/kg was administered intravenously as a single dose. |
| Part 1 - AIN457A 1.0 mg/kg | EXPERIMENTAL | AIN457A 1.0 mg/kg was administered intravenously as a single dose. |
| Part 1 - AIN457A 3.0 mg/kg | EXPERIMENTAL | AIN457A 3.0 mg/kg was administered intravenously as a single dose. |
| Parts 2 and 3 - AIN457A 1.0 mg/kg | EXPERIMENTAL | AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| Parts 2 and 3 - AIN457A 3.0 mg/kg | EXPERIMENTAL | AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| Parts 2 and 3 - AIN457A 10 mg/kg | EXPERIMENTAL | AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| Parts 2 and 3 - Placebo | PLACEBO_COMPARATOR | Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| Part 1 - Healthy Volunteers - AIN457A 3 mg/kg | EXPERIMENTAL | AIN457A 3.0 mg/kg was administered intravenously as a single dose. |
| Part 1 - Healthy Volunteers - AIN457A 10 mg/kg | EXPERIMENTAL | AIN457A 10 mg/kg was administered intravenously as a single dose. |
| Part 1 - Healthy Volunteers - Placebo | PLACEBO_COMPARATOR | Placebo to AIN457A was administered intravenously as a single dose. |
| Name | Type | Description |
|---|---|---|
| AIN457 | DRUG | Secukinumab 150 mg was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection |
| Secukinumab Placebo | OTHER | Secukinumab placebo was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection |
| AIN457 6 mg/kg i.v. | DRUG | AIN457 6 mg/kg delivered by i.v. infusion |
| Placebo | DRUG | Matching placebo to AIN457 i.v. infusion |
| AIN457 3 mg/kg | DRUG | AIN457 3 mg/kg delivered by i.v. infusion |
| AIN457 Placebo | DRUG | Placebo matching AIN457 |
| AIN457 (secukinumab) | DRUG | Is a recombinant monoclonal antibody which neutralizes the activity of IL-17A, and has been shown to be effective in treating patients with moderate-to-severe plaque psoriasis. Secukinumab 150 mg provided in 1 mL pre filled syringes (PFS) for s.c. injection. The 300 mg dose was administered as 2 × PFS injections. |
| AIN457 300 mg | DRUG | - |
| ustekinumab 45/90 mg | DRUG | - |
| placebo secukinumab | DRUG | Placebo |
| AIN457 150 mg | DRUG | (1 injection per dose) and placebo to Secukinumab 150 mg |
| Abatacept | BIOLOGICAL | Abatacept (from 500 to 1000 mg i.v. based on weight) was given as i.v. at baseline, weeks 2 and 4, and then every 4 weeks starting at week 8. |
| AIN457 150mg | DRUG | (1 injection per dose) and placebo to secukinumab 150 mg |
| AIN457 300mg | DRUG | secukinumab 150 mg (2 injections per dose) |
| AIN457A | DRUG | Induction with monthly injections - "Monthly": secukinumab (AIN457) 150 mg s.c. administered at weeks 1, 5, 9 |
| AIN 457 | DRUG | AIN457 low dose (i.v) |
| Midazolam | DRUG | midazolam administered to all patients Days -7, 1 and 35. |
| prednisolone | DRUG | - |
Inclusion Criteria: * Participant must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed. * Chinese male or non-pregnant, non-lactating Chinese...
AIN457 is an investigational monoclonal antibody being studied for immune-mediated inflammatory conditions. Clinical trials have evaluated it in rheumatoid arthritis, non-infectious uveitis, and Behcet's disease. It is also associated with chronic plaque-type psoriasis and multiple sclerosis indications, though the listed trials focus on the arthritis and uveitis conditions.
AIN457 is being developed by Novartis AG, which trades under the ticker NVS. The company has sponsored multiple clinical trials of the drug across different inflammatory conditions, including phase 1, phase 2, and phase 3 studies.
AIN457 has completed clinical trials in phases 1, 2, and 3. The most advanced completed trial is a phase 3 study in rheumatoid arthritis. It remains an investigational drug and is not approved, with no active trials currently listed.
AIN457 has completed four clinical trials. NCT00669942 was a phase 1 study in rheumatoid arthritis. NCT00685399 was a phase 2 trial in non-infectious uveitis. NCT00995709 was a phase 3 study in Behcet's disease. NCT01350804 was a phase 3 trial in rheumatoid arthritis.
Yes, AIN457 is also known as secukinumab. One clinical trial, NCT01350804, explicitly refers to secukinumab (AIN457) in its title, confirming that the two names refer to the same drug being developed by Novartis.
AIN457 is not FDA approved. It is an investigational drug that has completed clinical trials in phases 1, 2, and 3, but no approval status has been indicated. The drug remains in clinical development as an unapproved therapy.