Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Ustekinumab · 20 trials · 11 indications
Steady-state trough serum concentration of ustekinumab at Week 28 by baseline age groups will be reported.
Steady-state trough serum concentration of guselkumab at Week 28 by baseline age groups will be reported.
AUCss is defined as area under the curve at steady-state over a 12-week dosing interval of ustekinumab at Week 28 by baseline age groups.
AUCss is defined as area under the curve at steady-state over a dosing interval (4 or 8 weeks) of guselkumab at Week 28 by baseline age groups.
Percentage of Participants with jPsA achieving ACR pediatric 30 response at Week 24 will be reported. The ACR pediatric 30 response criteria is defined as a 30 percent (%) improvement (that is, a decrease in score) from baseline in greater than or equal to (\>=) 3 of the following 6 components, with worsening of \>=30% in no more than 1 of the following components: physician global assessment (PGA) of disease activity, patient/participant assessment of overall well-being, number of active joints (defined as swelling or loss of motion with pain and/or tenderness), number of joints with limited range of motion, physician function by childhood health assessment questionnaire (CHAQ) and C-reactive protein (CRP).
Percentage of Participants with jPsA achieving ACR pediatric 30 response at Week 24 will be reported. The ACR pediatric 30 response criteria is defined as a 30% improvement (that is, a decrease in score) from baseline in \>=3 of the following 6 components, with worsening of \>=30% in no more than 1 of the following components: PGA of disease activity, patient/participant assessment of overall well-being, number of active joints (defined as swelling or loss of motion with pain and/or tenderness), number of joints with limited range of motion, physician function by CHAQ and CRP.
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of participants with AEs leading to discontinuation of study intervention will be reported.
Number of participants with AEs of special interest (any newly identified malignancy case of active tuberculosis \[TB\], or opportunistic infection occurring after the first administration of study intervention\[s\]) will be reported.
Number of participants with abnormalities in clinical laboratory parameters (such as hematology and serum chemistry) will be reported.
Number of participants with injection-site reactions will be reported. An injection-site reaction is any adverse reaction at a subcutaneous (SC) study intervention injection-site.
Number of participants with AEs of worsening of the disease will be reported.
Number of participants with concomitant therapy due to loss of response will be reported.
Number of participants with clinical remission in induction period will be assessed. Clinical remission is defined as having a Pediatric Crohn's Disease Activity Index (PCDAI) score less than or equal to (\<=) 10 points. 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, abdominal tenderness or mass, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease.
Number of participants with reactions temporally associated with IV infusion in induction period will be reported.
Number of participants with SC injection-site reactions in maintenance period will be reported.
Serum ustekinumab concentrations will be reported.
Number of participants with clinical remission in maintenance period will be assessed. This will be assessed among participants who are in clinical response at induction week-8 (I-8). Clinical remission is defined as having a PCDAI score \<= 10 points. 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, abdominal tenderness or mass, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease.
Proportion of patients with steroid free clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) and fecal calprotectin\<250µg/g at week 48. \[stool frequency (ST): average number of liquid stools for 1 week abdominal pain (AP): average scoring for abdominal pain for 1 week (0=none; 1=mild, 2=moderate; 3= severe)\]
Percentage of participants with clinical remission at Week 52 were assessed. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of less than (\<) 150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.
Endoscopic response defined as showing a reduction from baseline in simple endoscopic score for Crohn's disease (SES-CD) of greater than or equal to (\>=) 50 percent (%). SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is sum of 4 variables for all 5 bowel segments. Scores range from 0-60 with higher scores indicating more severe disease. Randomized participants who stopped treatment before reaching Week 48 due to any reason, or participants without endoscopic data at Week 48 were analyzed as nonresponders.
The PGA is used to determine the participant's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participant's psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), marked (4), or severe (5). Higher scores indicate worse disease. Treatment Failure (TF) criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
As per global definition, clinical remission is defined as a Mayo score less than or equal to (\<=)2 points, with no individual subscore greater than (\>)1. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding \[RB\], endoscopy findings, and physician's global assessment \[PGA\]), rated as 0 (normal) to 3 (severe). Total score was calculated as the sum of 4 subscores and values range from 0 to 12 scores, where 3 to 5 = mild; 6 to 10 = moderate; and 11 to 12 = severe; higher scores indicate worsening of the disease. Participants who had a prohibited change in concomitant ulcerative colitis (UC) medication or an ostomy or colectomy prior to the Week 8 or who had all 4 Mayo subscores missing at Week 8 were considered not to be in clinical remission. Endoscopy subscore as assessed during central review of video of endoscopy was used.
As per US definition, clinical remission was defined as absolute stool number \<=3, a Mayo rectal bleeding subscore of 0 (no blood seen), and a Mayo endoscopy subscore of 0 (normal or inactive disease) or 1 (mild disease \[erythema, decreased vascular pattern, mild friability\]) without the physician's global assessment. Absolute stool number is average of daily stool number over the three days. The Mayo rectal bleeding and endoscopy findings subscores were rated as 0 (normal) to 3 (severe). Participants who had a prohibited change in concomitant UC medication or an ostomy or colectomy prior to the Week 8 or who were missing all 3 of the Mayo components pertaining to this outcome measure (OM) (absolute stool number, rectal bleeding subscore, and Mayo endoscopy subscore) at Week 8 were considered not to be in clinical remission. Endoscopy subscore as assessed during central review of the video of the endoscopy was used.
As per global definition, clinical remission was defined as a Mayo score \<=2 points, with no individual subscore \>1. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, endoscopy findings, and physician's global assessment), rated as 0 (normal) to 3 (severe). Total score was calculated as the sum of 4 subscores and values range from 0 to 12 scores, where 3 to 5 = mild; 6 to 10 = moderate; and 11 to 12 = severe; higher scores indicate worsening of the disease. Participants who had a prohibited change in UC medication or an ostomy or colectomy or used a rescue medication after clinical flare, or discontinued study agent due to lack of therapeutic effect or due to an AE of worsening of UC prior to the Week 44 or who had all 4 Mayo subscores missing at Week 44 were considered not to be in clinical remission. Endoscopy subscore as assessed during central review of the video of the endoscopy was used.
Per US definition, clinical remission: absolute stool number \<=3, a Mayo rectal bleeding subscore of 0 (no blood seen), and a Mayo endoscopy subscore of 0 (normal or inactive disease) or 1 (mild disease \[erythema, decreased vascular pattern, mild friability\]), without the physician's global assessment. Absolute stool number is average of daily stool number over the three days. The Mayo rectal bleeding and endoscopy findings subscores were rated as 0 (normal) to 3 (severe). Participants who had prohibited change in UC medication/ ostomy/ colectomy/ used rescue medication after clinical flare/ discontinued study agent due to lack of therapeutic effect/ due to AE of worsening of UC prior to Week 44 and who were missing all 3 of Mayo components pertaining to this OM (absolute stool number, rectal bleeding subscore, and Mayo endoscopy subscore) at Week 44 were considered not to be in clinical remission. Endoscopy subscore as assessed during central review of video of endoscopy was used.
The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).
Clinical responses for week (wk)28 sPGA responders randomized to every 12 weeks (q12wk) fixed-interval dosing (Group 1) vs. patient-tailored fixed-interval dosing (Group 2) were assessed using the static PGA (sPGA) measure. Investigators graded psoriasis lesions for induration (0=no plaque elevation to 5=severe plaque elevation), erythema (0=no evidence of erythema to 5=dusky to deep red coloration), and scaling (0=no evidence of scaling to 5=severe scaling). The sum of the 3 scales is divided by 3 and rounded to obtain a final sPGA score, defined as 0=cleared (except for residual discoloration), 1=minimal, 2=mild, 3=moderate, 4=marked or 5=severe.
An ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 20 percent improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 cm) 4) Participant's assessment of physical function as measured by the "Disability Index of the Health Assessment Questionnaire" (HAQ-DI) (score of 0-3 in 8 functional areas) and 5) C reactive protein.
Percentage of participants with \>=75% improvement in PASI score at Week 12 from Baseline was reported. PASI is a widely used tool for the measurement of severity of psoriasis. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. The scale ranges from 0 (best) to 72 (worst). Baseline visit refers to Week 0.
SRI-4 response was defined as greater than or equal to 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA). Composite response is defined as SRI-4 response in participants who do not meet treatment failure criteria. SLEDAI-2K assessment consists of 24 items with total score of 0 to 105, with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale = from very well (0)-very poor (10).
The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (greater than \[\>\] 90 percent \[%\]-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score.
The ALP response was defined as a greater than 40 percent (%) decrease from Baseline in ALP concentration at Week 12.
Serum samples will be analyzed to determine concentrations of ustekinumab using a validated, specific, and sensitive immunoassay method.
Cmax is maximum observed serum concentration of ustekinumab.
AUC (0-Infinite) defined as area under the serum concentration versus time curve from time zero to infinity with extrapolation of the terminal phase will be evaluated.
Serum samples will be collected to measure seum concentrations of Ustekinumab.
The Cmax is the maximum observed plasma concentration of study drug.
The AUC(0-inf) is the area under the serum concentration versus time curve from time zero to infinity with extrapolation of the terminal phase.
| Arm | Type | Description |
|---|---|---|
| Cohort 1: Ustekinumab | EXPERIMENTAL | Participants will receive a weight-based dose of ustekinumab subcutaneously (SC) at Week 0, Week 4 and then every 12 weeks up to Week 52. Cohort 1 is closed for further enrollment. |
| Cohort 2: Guselkumab | EXPERIMENTAL | The dose of guselkumab will be based on the participant's weight. Participants will receive guselkumab SC at Weeks 0 and 4 followed by either every 4 weeks (Q4W) (with historical radiographic evidence of joint damage) or every 8 weeks (Q8W) (without historical evidence of joint damage) dosing with the last dose at Week 52. Participants at high risk of joint damage can also be considered for Q4W dosing per investigator. |
| Ustekinumab | EXPERIMENTAL | Participants will have continued access to ustekinumab for primary study (CNTO1275CRD1001, CNTO1275PUC3001, CNTO1275CRD3004, CNTO1275JPA3001) participants who in the opinion of the investigator will continue to benefit from ustekinumab therapy. All blinded participants who enroll in the long-term extension (LTE) from blinded primary studies with both every 8 weeks (q8w) and every 12 weeks (q12w) dosing groups just prior to the end of the primary study will be assigned to the q8w dosing regimen. Participants enrolling in the LTE from an unblinded primary study will remain on the final dosing regimen that they were receiving in the primary study. Participants enrolling from the Exposure Optimization Substudy may be eligible to remain on the every 4 weeks (q4w) dosing regimen. |
| Open- Label Ustekinumab Intravenous (IV): Induction Period | EXPERIMENTAL | All participants will receive a single IV administration of ustekinumab at induction Week 0 (I-0) based on body surface area (BSA) (milligram per meter square \[mg/m\^2\]) or weight-tiered induction dose (milligram per kilogram \[mg/kg\]). |
| Ustekinumab Subcutaneous (SC) Every 8 Weeks (q8w): Maintenance Period | EXPERIMENTAL | Participants will receive SC administration of ustekinumab q8w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at maintenance weeks (Weeks M)-0, M-8, M-16, M-24, M 32, and M-40 and matching placebo at Weeks M-12 and M-36 to maintain the blind. |
| Ustekinumab SC Every 12 Weeks (q12w): Maintenance Period | EXPERIMENTAL | Participants will receive SC administration of ustekinumab q12w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at Weeks M-0, M-12, M-24, M-36 and matching placebo at Weeks M-8, M-16, M-32, and M-40 to maintain the blind. |
| 1. Subcutaneous ustekinumab every 8 weeks | PLACEBO_COMPARATOR | re-induction (≈6mg/kg) intravenous ustekinumab followed by 90 mg Subcutaneous ustekinumab every 8 weeks (Q8W) for 48 weeks - receiving Q8W placebo to mimic Q4W injections |
| 2. Subcutaneous ustekinumab every 4 weeks | ACTIVE_COMPARATOR | re-induction (≈6mg/kg) intravenous ustekinumab followed by 90 mg Subcutaneous ustekinumab every 4 weeks (Q4W) for 48 weeks |
| Group 1 (Ustekinumab) | EXPERIMENTAL | Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals. |
| Group 2 (Adalimumab) | ACTIVE_COMPARATOR | Participants will receive IV infusion of placebo for ustekinumab and 4 SC injections of adalimumab (each 40 mg, total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants will self-administer 1 SC injection of adalimumab 40 mg q2w. |
| All Participants | EXPERIMENTAL | At Week (Wk) 0, all eligible participants will initiate intravenous (IV) induction treatment with ustekinumab (UST) on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg). At Week 8, all participants will receive a 90 milligram (mg) subcutaneous (SC) injection of ustekinumab. At Week 16, participants who do not achieve a Crohn's Disease Activity Index (CDAI) improvement of greater than or equal to (\>=) 70 points versus Week 0 (CDAI 70) will leave the study. Remaining participants will be randomized in a 1:1 ratio to either one of two arms for open label maintenance treatment up to Week 48: the treat to target arm or the routine care arm. From Week 48, participants will continue ustekinumab treatment in the study extension period, up to Week 104. Dosing frequency will be adjusted in the extension period for the participants failing to meet the treatment target. |
| Routine Care Arm | EXPERIMENTAL | In the routine care arm, assessment visits will be scheduled according to the timing of maintenance treatment injections up to Week 48, which will be in compliance with the EU SmPC for ustekinumab for the treatment of Crohn's disease, in which dosing every 12 weeks is recommended. At Week 16, (that is, 8 weeks after the first SC dose) participants continuing in the study will have demonstrated a CDAI-70 response. Nonetheless, participants who have not shown adequate response based on the investigator's judgment may receive a second SC dose at Week 16. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion. |
| Treat to Target (T2T) Arm | EXPERIMENTAL | UST maintenance treatment assignment will be based on centrally-read colonoscopy (at Wk16). Participants with \<25% improvement in SES-CD score at Wk16 will be assigned to Q8 (8-weekly) treatment and will receive UST 90mg SC at Wk16. In contrast, participants with \>=25% improvement in SES-CD score at Wk16 will be assigned to Q12 treatment and will receive next UST dose (90 mg SC) at Wk20. At assessment visits (from Wk24 for participants assigned to the Q8 regimen or from Wk20 for the Q12 group) UST maintenance treatment (up to Wk 48) will be directed by T2T assessments. Participants meeting target will continue with same UST dosing frequency. The dosing frequency will be optimized for all participants failing to meet the target at assessment visit. Those previously on Q12 regimens will be adjusted to Q8 dosing; those previously on Q8 regimens will be adjusted to Q4 dosing. Participants subsequently failing to meet the target will not be able to adjust further and will leave the study. |
| Exploratory Extension period: From Week 48 to Week 104 | EXPERIMENTAL | At Week 48, dose de-escalation will be implemented for participants with both endoscopic remission (SES-CD score \<=2) and corticosteroid-free clinical remission of at least 16 weeks duration. Participants receiving 12 weekly dosing frequency (Q12) ustekinumab will maintain this dosing frequency. Participants with either clinical remission or endoscopic remission, but not both, at Week 48 will continue with same dosing frequency or de-escalate provided maintenance of corticosteroid-free clinical remission and biomarker remission at 2 consecutive visits. Participants with neither corticosteroid-free clinical remission nor endoscopic remission will escalate dose or leave study if already on 4 weekly dosing frequency (Q4) dose. If neither clinical remission nor biomarker remission is evident at the next visit, participant will leave study. Later in the extension period, only those who achieve corticosteroid-free clinical remission and biomarker remission will undergo dose de-escalation. |
| Ustekinumab Group | EXPERIMENTAL | Participants will receive 1 of the following dose levels depending on their weight: participants weighing less than (\<) 60 kg will receive Ustekinumab 0.75 milligram per kilogram (mg/kg); participants weighing greater than or equal to (\>=) 60 kg to less than or equal to (\<=) 100 kg will receive ustekinumab 45 mg; participants weighing \>100 kg will receive ustekinumab 90 mg, at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants who enter the long-term extension (LTE) period will continue receiving ustekinumab every 12 weeks (q12w) beginning at Week 56 up to Week 248. |
| Induction Study - Placebo Intravenous (IV) | PLACEBO_COMPARATOR | Participants will be randomized to receive single dose of placebo as Intravenous (IV: into the vein) infusion at Week 0. Participants with clinical response at Week 8 will be eligible to enter the Maintenance study, but will not be randomized. |
| Induction Study - Ustekinumab 130 milligram (mg) IV | EXPERIMENTAL | Participants will be randomized to receive single dose of ustekinumab 130 mg as IV infusion at Week 0. Participants with clinical response at Week 8 will be eligible to enter the Maintenance study and will be randomized. |
| Induction Study - Ustekinumab 6 mg/kg IV | EXPERIMENTAL | Participants will be randomized to receive ustekinumab approximating 6 mg/kg of body weight, as intravenous infusion at Week 0. Participants with clinical response at Week 8 will be eligible to enter the Maintenance study and will be randomized. |
| Induction Study- Placebo- Nonresponsders at Week 8 | OTHER | Participants without clinical response to placebo at Week 8 will receive a single IV infusion of ustekinumab approximating 6mg/kg along with matching subcutaneous (SC) placebo (to maintain the blind). Participants in clinical response at Week 16 will be eligible to enter Maintenance study and will be randomized. |
| Induction study-Ustekinumab Nonresponders at Week 8 | OTHER | Participants without clinical response to ustekinumab (130 mg or 6 mg/kg \[IV\]) at Week 8 will receive a single dose of ustekinumab 90 mg subcutaneously along with matching placebo intravenously (to maintain the blind). Participants in clinical response at Week 16 (that is, delayed responders) will be eligible to enter Maintenance study, but will not be randomized. |
| Maintenance Study - Placebo Subcutaneous (SC) | PLACEBO_COMPARATOR | Participants in clinical response (at Week 8 or Week 16) to Induction treatment with single IV infusion of Ustekinumab will be randomized to receive placebo subcutaneously, beginning Week 0 of Maintenance study through Week 44. |
| Maintenance Study - Ustekinumab 90mg SC every 12 weeks | EXPERIMENTAL | Participants in clinical response (at Week 8 or Week 16) to Induction treatment with single IV infusion of Ustekinumab will be randomized to receive ustekinumab 90 mg subcutaneously every 12 weeks, beginning Week 0 of Maintenance study through Week 44. |
| Maintenance Study - Ustekinumab 90mg SC every 8 weeks (q8w) | EXPERIMENTAL | Participants in clinical response (at Week 8 or Week 16) to Induction treatment with single IV infusion of Ustekinumab will be randomized to receive ustekinumab 90 mg subcutaneously every 8 weeks, beginning Week 0 of Maintenance study through Week 44. |
| Maintenance Study - Placebo IV - Responder - Placebo SC | OTHER | Participants in clinical response to Induction treatment with IV Placebo will receive placebo subcutaneously, beginning Week 0 of Maintenance study through Week 44. Participants are not randomized. |
| Maintenance Study-Delayed Responder-Ustekinumab 90mg SC q8w | OTHER | Participants without clinical response to induction treatment ustekinumab (130 mg or 6 mg/kg \[IV\]) at Week 8 but in clinical response at Week 16 after receiving Induction Ustekinumab at week 8 (delayed responders) will receive ustekinumab 90 mg subcutaneously every 8 weeks, beginning Week 0 of Maintenance study through Week 44. Participants are not randomized. |
| Open-label ustekinumab | EXPERIMENTAL | - |
| Double-blind guselkumab | EXPERIMENTAL | - |
| Double-blind ustekinumab | EXPERIMENTAL | - |
| Group 1: Approved q12w maintenance regimen | EXPERIMENTAL | Active ustekinumab study agent q12 weeks with sham/placebo as necessary to maintain blind |
| Group 2: Subject-tailored fixed-interval maintenance regimen | EXPERIMENTAL | Subjects will undergo placebo withdrawal and will receive active study agent up to q24w intervals with sham/placebo injections to maintain the blind. |
| Placebo | EXPERIMENTAL | Participants will receive subcutaneous (SC) injections of placebo at Weeks 0, 4, 16, and 20. At Week 24 participants will cross over to receive SC injections of ustekinumab 45 mg at Weeks 24 and 28 and every 12 weeks thereafter with the last dose at Week 40. If early escape, SC injections of 45 mg ustekinumab will be given at Weeks 16, 20, and 28 and every 12 weeks thereafter with the last dose at Week 40. For participants entering early escape, a SC placebo injection will be given at Week 24 to maintain the blind. |
| Ustekinumab 45 mg | EXPERIMENTAL | Participants will receive SC injections of ustekinumab 45 mg at Weeks 0 and 4 and every 12 weeks thereafter with the last dose at Week 40. If early escape, SC injections of 90 mg ustekinumab will be given at Week 16 and every 12 weeks thereafter with the last dose at Week 40. Participants will receive SC injections of placebo at Weeks 20 and 24 to maintain the blind. |
| Ustekinumab 90 mg | EXPERIMENTAL | Participants will receive SC injections of ustekinumab 90 mg at Weeks 0 and 4 and every 12 weeks thereafter with the last dose at Week 40. If early escape, the same dosage schedule will continue. Participants will receive SC injections of placebo at Weeks 20 and 24 to maintain the blind. |
| Placebo (CP) | PLACEBO_COMPARATOR | Placebo 0.5 ml and 1.0 ml will be administered subcutaneously (SC) on Weeks 0 and 4 respectively during the controlled period (Weeks 0-12). |
| Ustekinumab 45 mg (CP) | ACTIVE_COMPARATOR | Ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) will be administered SC on Weeks 0 and 4 during controlled period (Weeks 0-12). |
| Ustekinumab 90 mg (CP) | ACTIVE_COMPARATOR | Ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) will be administered SC on Weeks 0 and 4 during controlled period (Weeks 0-12). |
| Placebo A (After CP) | PLACEBO_COMPARATOR | After the controlled period (that is \[i.e.\], during the active drug treatment period \[Weeks 12-64\]), the placebo group will be randomized into 2 groups, including Placebo A, in which ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) will be administered SC at Weeks 12, 16, 28, 40, and 52. |
| Placebo B (After CP) | PLACEBO_COMPARATOR | After the controlled period (i.e., during the active drug treatment period \[Weeks 12-64\]), the placebo group will be randomized into 2 groups, including Placebo B, in which ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) will be administered SC at Weeks 12, 16, 28, 40, and 52. |
| Ustekinumab 45 mg (After CP) | ACTIVE_COMPARATOR | After the controlled period (i.e., during the active drug treatment period \[Weeks 12-64\]), participants in the ustekinumab 45 mg group will receive placebo (0.5 ml and 1.0 ml) SC at Week 12 followed by ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) SC at Weeks 16, 28, 40 and 52. |
| Ustekinumab 90 mg (After CP) | ACTIVE_COMPARATOR | After the controlled period (i.e., during the active drug treatment period \[Weeks 12-64\]), participants in the ustekinumab 90 mg group will receive placebo (0.5 ml and 1.0 ml) SC at Week 12 followed by ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) SC at Weeks 16, 28, 40 and 52. |
| Ustekinumab plus Concomitant Medication | EXPERIMENTAL | Participants will receive weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0 followed by ustekinumab 90 mg subcutaneously (SC) every 8 weeks (q8w) up to Week 40. Participants who meet the study extension inclusion criteria will continue to receive ustekinumab 90 mg SC q8w starting at Week 48 or 56 through Week 104. Participants will continue stable concomitant treatment through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. Participants who complete or discontinue study treatment will be evaluated for 16 additional Weeks of safety follow-up. |
| Placebo followed by Ustekinumab plus Concomitant Medication | EXPERIMENTAL | Participants will receive placebo intravenously at Week 0 followed by placebo subcutaneously at Weeks 8 and 16. At week 24 participants will receive ustekinumab SC q8w up to Week 40. Participants who meet the study extension inclusion criteria will continue to receive ustekinumab 90 mg SC q8w starting at Week 48 or 56 through Week 104. Participants will continue stable concomitant treatment through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. Participants who complete or discontinue study treatment will be evaluated for 16 additional Weeks of safety follow-up. |
| Open-label: ustekinumab 90 mg | EXPERIMENTAL | - |
| Double-blind: ustekinumab 45 mg | EXPERIMENTAL | - |
| Double-blind: ustekinumab 90 mg | EXPERIMENTAL | - |
| Double-blind: ustekinumb 180 mg | EXPERIMENTAL | - |
| Double-blind: placebo | PLACEBO_COMPARATOR | - |
| Cohort 1: Juvenile Psoriatic Arthritis (jPsA) | EXPERIMENTAL | Participants (aged greater than or equal to \[\>=\] 5 to less than \[\<\] 18 years) will receive ustekinumab at the dose and frequency as prescribed by their treating health care professional (HCP). |
| Cohort 2: Pediatric Psoriasis (PsO) | EXPERIMENTAL | Participants (aged \>=6 to \<18 years) will receive ustekinumab at the dose and frequency as prescribed by their treating HCP. |
| Ustekinumab (Using Reference Device) | ACTIVE_COMPARATOR | Participants will receive a single subcutaneous (SC) injection of ustekinumab in Device 1 as a reference device on Day 1. |
| Ustekinumab (Using Test Device) | EXPERIMENTAL | Participants will receive a single SC injection of ustekinumab in Device 2 as a test device on Day 1. |
| Group1: Ustekinumab Dose Regimen 1 | EXPERIMENTAL | Subjects will receive a single intravenous (IV) induction dose of 3 milligram per kilogram (mg/kg) for subjects less than \< 40 kilogram (kg) or 130 milligram (mg) for subjects greater than or equal to \>= 40 kg at Week 0 followed by subcutaneous (SC) maintenance dose of 2 mg/kg for subjects \< 40 kg or 90 mg for subjects \>= 40 kg at week 8. |
| Group2: Ustekinumab Dose Regimen 2 | EXPERIMENTAL | Subjects will receive a single Intravenous (IV) dose of 9 mg/kg for subjects \<40 kg or 390 mg for subjects \>= 40 kg at Week 0 followed by SC maintenance dose of 2 mg/kg for subjects \<40 kg or 90 mg for subjects \>= 40 kg at week 8. |
| Ustekinumab 90 mg/mL | EXPERIMENTAL | - |
| Ustekinumab 5 mg/mL | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Ustekinumab | DRUG | Ustekinumab will be administered as subcutaneous injection. |
| Guselkumab | DRUG | Guselkumab will be administered as subcutaneous injection. |
| Placebo | DRUG | Matching placebo will be administered as SC injection. |
| Placebo for Ustekinumab | BIOLOGICAL | Participants will receive placebo as SC injection to blind adalimumab. |
| Placebo for Adalimumab | BIOLOGICAL | Participants will receive placebo as IV infusion to blind ustekinumab. |
| Ustekinumab (6 mg/kg) | BIOLOGICAL | Participants will receive ustekinumab 6 mg/kg (weight based dosing) as IV infusion. |
| Ustekinumab (90 mg) | BIOLOGICAL | Participants will self-administer SC injection of ustekinumab 90 mg. |
| Adalimumab (40 mg) | BIOLOGICAL | Participants will self-administer multiple SC injections of adalimumab (each 40 mg) and will receive total dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg q2w from Week 4 to 56. |
| Ustekinumab 0.75 mg/kg | DRUG | Participants weighing less than (\<) 60 kilograms will receive ustekinumab 0.75 milligram per kilogram (mg/kg) at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants for LTE period will continue to receive ustekinumab 0.75 mg/kg up to Week 248. |
| Ustekinumab 45 mg | DRUG | Participants weighing greater than or equal to (\>=) 60 kg to less than or equal to (\<=) 100 kg will receive ustekinumab 45 mg at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants for LTE period will continue to receive ustekinumab 45 mg up to Week 248. |
| Ustekinumab 90 mg | DRUG | Participants weighing \>100 kg will receive ustekinumab 90 mg at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants for LTE period will continue to receive ustekinumab 90 mg up to Week 248. |
| Placebo IV | DRUG | Placebo will be administered as intravenous infusion. |
| Placebo SC | DRUG | Placebo will be administered Subcutaneously. |
| Ustekinumab IV | DRUG | Ustekinumab will be administered as intravenous infusion at Week 0 or Week 8 in Induction Study. |
| Ustekinumab SC | DRUG | Ustekinumab will be administered as subcutaneously. |
| Placebo for guselkumab | DRUG | Subcutaneous injection at Weeks 16 and 20 and q8w thereafter through Week 44 to maintain the blind for participants randomized to treatment with ustekinumab. |
| Placebo (CP) | DRUG | Placebo 0.5 ml and 1.0 ml will be administered subcutaneously (SC) on Weeks 0 and 4 respectively during the controlled period (Weeks 0-12). |
| Ustekinumab 45 mg (CP) | DRUG | Ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) will be administered SC on Weeks 0 and 4 during controlled period (Weeks 0-12). |
| Ustekinumab 90 mg (CP) | DRUG | Ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) will be administered SC on Weeks 0 and 4 during controlled period (Weeks 0-12). |
| Placebo A (After CP) | DRUG | After the controlled period (i.e., during the active drug treatment period \[Weeks 12-64\]), the placebo group will be randomized into 2 groups, including Placebo A, in which ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) will be administered SC at Weeks 12, 16, 28, 40, and 52. |
| Placebo B (After CP) | DRUG | After the controlled period (i.e., during the active drug treatment period \[Weeks 12-64\]), the placebo group will be randomized into 2 groups, including Placebo B, in which ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) will be administered SC at Weeks 12, 16, 28, 40, and 52. |
| Ustekinumab 45 mg (After CP) | DRUG | After the controlled period (i.e., during the active drug treatment period \[Weeks 12-64\]), participants in the ustekinumab 45 mg group will receive placebo (0.5 ml and 1.0 ml) SC at Week 12 followed by ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) SC at Weeks 16, 28, 40 and 52. |
| Ustekinumab 90 mg (After CP) | DRUG | After the controlled period (i.e., during the active drug treatment period \[Weeks 12-64\]), participants in the ustekinumab 90 mg group will receive placebo (0.5 ml and 1.0 ml) SC at Week 12 followed by ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) SC at Weeks 16, 28, 40 and 52. |
| Placebo Infusion | DRUG | Placebo intravenously at Week 0. |
| Concomitant Medication | OTHER | Concomitant treatment (mycophenolate, azathioprine/6-mercaptopurine, methotrexate, hydroxychloroquine and/or chloroquine, oral corticosteroids, NSAIDs, antihypertensive medications, and topical medications) through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. |
| Concomitant topical medications for atopic dermatitis | OTHER | Concomitant topical medications (as defined in the protocol) can be used from 4 weeks prior to randomization and throughout the study. However, the dosage cannot be increased and new medications cannot be added until after Week 12. |
| ustekinumab 180 mg | DRUG | Subcutaneous injections of ustekinumb 180 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose. |
Inclusion Criteria: * Diagnosis of juvenile psoriatic arthritis (jPsA) by Vancouver criteria with exclusion of enthesitis-related arthritis (ERA). Diagnosis made \>=3 months (that is, 90 days) prior to screening * Active disease in at least greater than or equal to (\>=) 3 joints at screening and a...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Sanofi SA Sponsored ADR | SNY | 6 | PHASE3 | Duvakitug |
| Eli Lilly and Company | LLY | 8 | PHASE3 | Mirikizumab |
| AbbVie, Inc. | ABBV | 14 | PHASE3 | Risankizumab, Risankizumab On-Body Injector |
| Johnson & Johnson | JNJ | 13 | PHASE3 | Ustekinumab |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 17 | PHASE3 | Vedolizumab |
| Merck & Co., Inc. | MRK | 2 | PHASE3 | Tulisokibart |
| AstraZeneca PLC | AZN | 2 | PHASE2 | AZD7798 |
| Disc Medicine, Inc. | IRON | 1 | PHASE2 | DISC-0974 |
| Spyre Therapeutics, Inc | SYRE | 1 | PHASE2 | SPY001, SPY002, SPY003 |
| Abivax SA Sponsored ADR | ABVX | 1 | PHASE2 | Obefazimod |
| Palisade Bio, Inc. | PALI | 1 | PHASE1 | PALI-2108 |
| Novartis AG Sponsored ADR | NVS | 1 | - | Undisclosed |
| Amgen Inc. | AMGN | 1 | N/A | Undisclosed |
| TScan Therapeutics, Inc. | TCRX | 1 | - | Undisclosed |