A Study of Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics (PK), efficacy, safety and immunogenicity of ustekinumab and guselkumab in active juvenile psoriatic arthritis (jPsA).

Detailed Description
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Juvenile psoriatic arthritis is a complex, chronic, progressive, debilitating musculoskeletal disease with significant remaining medical need. There is a need for medications which have a similar efficacy profile and a similar safety profile relative to currently available treatment for jPsA which include anti-tumor necrosis factor alpha (TNF alpha) inhibitors and secukinumab. STELARA (ustekinumab) is a fully human immunoglobulin G (IgG) 1 kappa monoclonal antibody (mAb) which binds with high affinity to the p40 subunit common to both interleukin (IL)-12 and IL 23 preventing IL-12/23p40 binding to the IL 12 Rb1 cell surface receptor shared by both cytokines. Through this mechanism of action, ustekinumab effectively neutralizes IL-12 T helper 1- and IL-23 T helper 17-mediated cellular responses. TREMFYA (guselkumab) is a fully human IgG1 lambda (G1 lambda) mAb that binds to the p19 subunit of human IL-23 with high affinity. The binding of guselkumab to IL-23 blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23-specific intracellular signaling and subsequent activation and cytokine production. This study consists of Screening period (up to 6 weeks), Treatment period (up to 52 weeks) and a final safety visit at Week 68. The total duration of the study is up to 68 weeks.

Official Title
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A Phase 3 Multicenter, Open-label Study to Evaluate the Efficacy, Pharmacokinetics, Safety, and Immunogenicity of Subcutaneously Administered Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis (PSUMMIT-Jr)

Conditions
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Arthritis, Juvenile

Intervention / Treatment
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* Drug: Ustekinumab
* Drug: Guselkumab


Participation Criteria
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Eligibility Criteria
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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 at week 0 (defined as swelling or loss of motion with pain and/or tenderness. Swelling alone meets the criteria for an active arthritic joint. In the absence of swelling, loss of motion with pain or tenderness or both pain and tenderness meet the criteria for an active arthritic joint Have active disease despite previous non-biologic disease modifying anti-rheumatic drug (DMARD) and/or non-steroidal anti-inflammatory drug (NSAID) therapy: Non-biologic DMARD therapy is defined as taking a non-biologic DMARD for at least 12 weeks or evidence of intolerance; NSAID therapy is defined as taking an NSAID for at least 4 weeks or evidence of intolerance Concurrent use of methotrexate, sulfasalazine, leflunomide, oral corticosteroids or NSAIDs is permitted but must be on stable dose Participants must be up to date with all immunizations in agreement with current local immunization guidelines for immunosuppressed patients Prior use of anti-TNFα agents, IL-17 inhibitors and other biologics (except non-responders to IL-23 inhibitors) and JAK inhibitors are permitted with sufficient washout period Exclusion Criteria: Participants with enthesitis-related arthritis (ERA) Have a history of latent or active granulomatous infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis prior to screening Have a history of, or ongoing, chronic or recurrent infectious disease Has evidence of herpes zoster infection within 8 weeks prior to Week 0 Have a known history of hepatitis C infection or test positive at screening

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Ustekinumab<br>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. | Drug: Ustekinumab<br>* Ustekinumab will be administered as subcutaneous injection.<br>* Other names: STELARA;|
| Experimental: Cohort 2: Guselkumab<br>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. | Drug: Guselkumab<br>* Guselkumab will be administered as subcutaneous injection.<br>* Other names: TREMFYA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Steady-state Trough Serum Concentration of Ustekinumab at Week 28 by Baseline Age Groups | Steady-state trough serum concentration of ustekinumab at Week 28 by baseline age groups will be reported. | Week 28 | 
| Cohort 2: Steady-state Trough Serum Concentration of Guselkumab at Week 28 by Baseline Age Groups | Steady-state trough serum concentration of guselkumab at Week 28 by baseline age groups will be reported. | Week 28 | 
| Cohort 1: Area Under the Curve at Steady-state (AUCss) 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 12-week dosing interval of ustekinumab at Week 28 by baseline age groups. | Week 28 | 
| Cohort 2: AUCss Over a Dosing Interval (4 or 8 Weeks) of Guselkumab 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. | Week 28 | 
| Cohort 1: Percentage of Participants with Juvenile Psoriatic Arthritis (jPsA) Achieving American College of Rheumatology (ACR) Pediatric 30 Response at Week 24 | 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). | Week 24 | 
| Cohort 2: Percentage of Participants with jPsA Achieving ACR Pediatric 30 Response at Week 24 | 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. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohorts 1: Steady-state Trough Serum Concentration of Ustekinumab at Week 52 by Baseline Age Groups | Steady-state trough serum concentration of ustekinumab at Week 52 by baseline age groups will be reported. | Week 52 | 
| Cohorts 2: Steady-state Trough Serum Concentration of Guselkumabat at Week 52 by Baseline Age Groups | Steady-state trough serum concentration of guselkumab at Week 52 by baseline age groups will be reported. | Week 52 | 
| Cohort 1: AUCss Over a 12-Week Dosing Interval of Ustekinumab at Week 52 by Baseline Age Groups | AUCss is defined as area under the curve at steady-state over a 12-week dosing interval of ustekinumab at Week 52 by baseline age groups. | Week 52 | 
| Cohort 2: AUCss Over a Dosing Interval (4 or 8 Weeks) of Guselkumab at Week 52 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 52 by baseline age groups. | Week 52 | 
| Cohorts 1 and 2: Percentage of Participants Achieving ACR Pediatric 30 Response at Weeks 4, 8, 12, 16, and 52 | 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. | Weeks 4, 8, 12, 16 and 52 | 
| Cohorts 1 and 2: Percentage of Participants Achieving ACR Pediatric 50 and 70 Responses at Weeks 4, 8, 12, 16, 24, and 52 | The ACR pediatric 50 and 70 responses are defined as a 50% improvement or 70% 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: 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. | Weeks 4, 8, 12, 16, 24, and 52 | 
| Cohorts 1 and 2: Time to Response Measured as Time to Achieving ACR Pediatric 30 | Time to response measured as time to achieving ACR pediatric 30 will be reported. | Baseline, up to Week 24 | 
| Cohorts 1 and 2: Change from Baseline in Clinical Juvenile Arthritis Disease Activity Score (cJADAS) 10 at Weeks 4, 8, 12, 16, 24, and 52 | Change from baseline in cJADAS 10 at Weeks 4, 8, 12, 16, 24, and 52 will be reported. The cJADAS is calculated as the sum of the scores of its 3 components: (1) physician global rating of overall disease activity, measured on a 10-cm horizontal visual analog scale; (2) parent/child ratings of well-being, assessed on a 10 cm horizontal line VAS; (3) number of active joints, assessed in 10 joints, for a total score ranging from 0 to 30 where 0=no activity and 30=maximum activity. | Baseline, up to Weeks 4, 8, 12, 16, 24, and 52 | 
| Cohorts 1 and 2: Change from Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 10, 27 and 71 at Weeks 4, 8, 12, 16, 24, and 52 | Change from baseline in JADAS 10, 27 and 71 at Weeks 4, 8, 12, 16, 24, and 52 will be reported. The JADAS is calculated as the sum of the scores of its 4 components: (1) physician global rating of overall disease activity, measured on a 10-cm horizontal visual analog scale; (2) parent/child ratings of well-being, assessed on a 10 cm horizontal line VAS; (3) number of active joints, assessed in 71, 27, or 10 joints (for JADAS 71, JADAS 27, and JADAS 10, respectively); (4) CRP (truncated to 0-10 mg/dL). | Baseline, up to Weeks 4, 8, 12, 16, 24, and 52 | 
| Cohorts 1 and 2: Change from Baseline in Psoriasis Area Severity Index (PASI) Score at Week 24 | Change from baseline in PASI score at Week 24 among the participants with greater than or equal to (>=) 3% body surface area (BSA) psoriatic involvement and a PGA psoriasis score of >=2 (mild) at baseline will be reported. The PASI includes assessments of 4 areas of the body: the head and neck, the arms, the trunk, and the legs. The percentage of skin in each area affected by psoriasis is given a numeric score representing the proportion involved. The severity of the 3 plaque signs of erythema, thickness/induration, and desquamation/scaling, is assessed on a 5-point scale. The total PASI score is from 0-72, where 0=no disease and 72=more disease. | Baseline and Week 24 | 
| Cohorts 1 and 2: Percentage of Participants with Adverse Events (AEs) | 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. | Up to Week 68 | 
| Cohorts 1 and 2: Percentage of Participants with Serious Adverse Events (SAEs) | A SAE is any untoward medical occurrence that at any dose results in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Up to Week 68 | 
| Cohorts 1 and 2: Percentage of Participants with Reasonably Related AEs | Percentage of participants with reasonably related AEs (including injection-site reactions and infections) will be reported. | Up to Week 68 | 
| Cohorts 1: Number of Participants with Antibodies to Ustekinumab | Number of participants with antibodies to ustekinumab (including peak titers) will be reported. | Weeks 52 and 68 | 
| Cohorts 2 : Number of Participants with Antibodies to Guselkumab | Number of participants with antibodies to guselkumab (including peak titers) will be reported. | Weeks 52 and 68 |