PSUMMIT-Jr: A Study of Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the pharmacokinetics (PK) and efficacy of ustekinumab and guselkumab in juvenile psoriatic arthritis (jPsA).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
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 (though mostly off-label) 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: Ustekinumab 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
Ustekinumab will be administered as subcutaneous injection.
Other Names:
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| Experimental: Cohort 2: Guselkumab Participants without evidence of joint damage will be dosed with guselkumab at Week 0, Week 4 and then every 8 weeks up to Week 52. Participants with radiographic evidence of joint damage will be dosed with guselkumab every 4 weeks from Week 0 through Week 52. Participants at high risk of joint damage according to clinical judgement but should be considered for dosing every 4 weeks, depending upon the judgement of the study doctor. |
Drug: Guselkumab
Guselkumab will be administered as subcutaneous injection.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Cohort 1: Observed Steady-state Trough Serum Concentration of Ustekinumab [Week 28]
Observed steady-state trough serum concentration of ustekinumab will be reported.
- Cohort 2: Observed Steady-state Trough Serum Concentration of Guselkumab [Week 28]
Observed steady-state trough serum concentration of guselkumab will be reported.
- 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 [Week 28]
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.
- Cohort 2: AUCss Over a Dosing Interval (4 or 8 Weeks) of Guselkumab at Week 28 by Baseline Age Groups [Week 28]
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.
- Cohort 1: Percentage of Participants with Juvenile Psoriatic Arthritis (jPsA) Achieving American College of Rheumatology (ACR) Pediatric 30 Response [Week 24]
Percentage of participants with jPsA achieving ACR pediatric 30 response 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 (>) 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).
- Cohort 2: Percentage of Participants with jPsA Achieving ACR Pediatric 30 Response [Week 24]
Percentage of participants with jPsA achieving ACR pediatric 30 response 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.
Secondary Outcome Measures
- Cohorts 1 and 2: Observed Steady-state Trough Serum Concentration of Ustekinumab and Guselkumab [Week 52]
Observed steady-state trough serum concentration of ustekinumab and guselkumab will be reported.
- Cohort 1: AUCss Over a 12-Week Dosing Interval of Ustekinumab at Week 52 by Baseline Age Groups [Week 52]
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.
- Cohort 2: AUCss Over a Dosing Interval (4 or 8 Weeks) of Guselkumab at Week 52 by Baseline Age Groups [Week 52]
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.
- Cohorts 1 and 2: Percentage of Participants Achieving ACR Pediatric 30 Response [Weeks 4, 8, 12, 16, 24 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.
- Cohorts 1 and 2: Percentage of Participants Achieving ACR Pediatric 50 and 70 Responses [Weeks 4, 8, 12, 16, 24, and 52]
The ACR 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.
- Cohorts 1 and 2: Time to Response Measured as Time to Achieving ACR Pediatric 30 [Baseline, up to Week 24]
Time to response measured as time to achieving ACR pediatric 30 will be reported.
- Cohorts 1 and 2: Change from Baseline in Clinical Juvenile Arthritis Disease Activity Score (cJADAS) 10 at Weeks 4, 8, 12, 16, 24, 28, and 52 [Baseline, up to Weeks 4, 8, 12, 16, 24, 28, and 52]
Change from baseline in cJADAS 10 at Weeks 4, 8, 12, 16, 24, 28, and 52 will be reported. The JADAS is computed by assessing the following variables: 1) physician global rating of overall disease activity; 2) parent/child ratings of well-being and pain; 3) number of active joints, assessed as 71, 27 and 10 (JADAS 71, 27, and 10 respectively); 4) CRP. cJADAS10 is a simple sum of active joint count (capped at a maximum of 10) plus physician global rating, plus parent/child assessment of well-being.
- 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, 28, and 52 [Baseline, up to Weeks 4, 8, 12, 16, 24, 28, and 52]
Change from baseline in JADAS 10, 27 and 71 at Weeks 4, 8, 12, 16, 24, 28, and 52 will be reported. The JADAS is computed by assessing the following variables: 1) physician global rating of overall disease activity; 2) parent/child ratings of well-being and pain; 3) number of active joints, assessed as 10, 27 and 71 (JADAS 10, 27, and 71 respectively); 4) CRP.
- Cohorts 1 and 2: Psoriasis Area Severity Index (PASI) Response Between Baseline and Week 24 [Baseline and Week 24]
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.
- Cohorts 1 and 2: Percentage of Participants with Adverse Events (AEs) [Up to Week 68]
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.
- Cohorts 1 and 2: Percentage of Participants with Serious Adverse Events (SAEs) [Up to Week 68]
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.
- Cohorts 1 and 2: Percentage of Participants with Reasonably Related AEs [Up to Week 68]
Percentage of participants with reasonably related AEs (including injection-site reactions and infections) will be reported.
- Cohorts 1 and 2 : Number of Participants with Antibodies to Ustekinumab and Guselkumab [Up to Week 68]
Number of participants with antibodies to ustekinumab and guselkumab (including peak titers) will be reported.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of juvenile psoriatic arthritis (jPsA) by Vancouver criteria with exclusion of enthesitis-related arthritis (ERA). Diagnosis made at least 12 weeks 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
-
Inadequate response (>= 4 weeks) or intolerance to >=1 non-steroidal anti-inflammatory drug (NSAID)
-
Inadequate response (>=12 weeks) or intolerance to >=1 non-biological disease modifying anti-rheumatic drug (DMARD)
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If using corticosteroids; must be on a stable dose of less than or equal to (<=) 10 milligrams (mg) prednisone equivalent or 0.20 mg per kilograms (kg) per day (whichever is less) for >=4 weeks before first administration of study intervention. If currently not using corticosteroids, the participant must have not received corticosteroids (intra articular, intramuscular, or intravenous [IV] corticosteroids [including intramuscular corticotropin]) for >=4 weeks before the first dose administration
Exclusion Criteria:
-
Participants with 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Childrens Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 2 | Nemours Children's Hospital/Endocrinology | Orlando | Florida | United States | 32827 |
| 3 | University of Chicago Medical Center | Chicago | Illinois | United States | 60637-1447 |
| 4 | Harvard Medical School - Boston Children's Hospital | Boston | Massachusetts | United States | 02215-5450 |
| 5 | Montefiore Medical Center | Bronx | New York | United States | 10467-2403 |
| 6 | Northwell Health | New York | New York | United States | 11040 |
| 7 | University of North Carolina | Chapel Hill | North Carolina | United States | 27514 |
| 8 | Legacy Emanuel Medical Center | Portland | Oregon | United States | 97227 |
| 9 | University of Utah | Salt Lake City | Utah | United States | 84132 |
| 10 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 11 | STAT Research S.A. | Ciudad Autonoma Buenos Aires | Argentina | C1013AAAB | |
| 12 | Hospital de Ninos de Cordoba | Cordoba | Argentina | 5000 | |
| 13 | Instituto Medico Platense | La Plata | Argentina | B1900 | |
| 14 | Centro Medico Privado de Reumatologia | San Miguel De Tucuman | Argentina | T4000AXL | |
| 15 | CHU de Caen | Caen | France | 14033 | |
| 16 | Hopital de Bicetre | Le Kremlin Bicêtre | France | 94270 | |
| 17 | CHU de Toulouse Hopital des Enfants | Toulouse cedex 9 | France | 31059 | |
| 18 | Hôpital D'Enfants | Vandoeuvre les Nancy | France | 54511 | |
| 19 | Helios Kliniken Berlin Buch Gmbh | Berlin | Germany | 13125 | |
| 20 | Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum | Berlin | Germany | 13353 | |
| 21 | Schön Klinik Hamburg Eilbek | Hamburg | Germany | 22081 | |
| 22 | Asklepios Klinik Sankt Augustin | Sankt Augustin | Germany | 53757 | |
| 23 | Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia Presidio Spedali Civili | Brescia | Italy | 25100 | |
| 24 | Istituto Giannina Gaslini | Genova | Italy | 16147 | |
| 25 | Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO | Milano | Italy | 20122 | |
| 26 | Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico | Milano | Italy | 20122 | |
| 27 | Hosp. Univ. Vall D Hebron | Barcelona | Spain | 08035 | |
| 28 | Hosp. Gral. Univ. Gregorio Marañon | Madrid | Spain | 28007 | |
| 29 | Hosp. Univ. La Paz | Madrid | Spain | 28046 | |
| 30 | Hosp. Clinico Univ. de Santiago | Santiago de Compostela | Spain | 15706 | |
| 31 | Hosp. Infanta Luisa | Sevilla | Spain | 41010 | |
| 32 | Hosp. Univ. I Politecni La Fe | Valencia | Spain | 46026 | |
| 33 | Hacettepe Universitesi Hastanesi | Ankara | Turkey | 6230 | |
| 34 | Istanbul University Cerrahpasa Medical Faculty | Istanbul | Turkey | 34098 | |
| 35 | Umraniye Training and Research Hospital | Istanbul | Turkey | 34766 | |
| 36 | Birmingham Children's Hospital | Birmingham | United Kingdom | B4 6NH | |
| 37 | Great Ormond Street Hospital | London | United Kingdom | WC1N 3JH | |
| 38 | Royal Victoria Infirmary | Newcastle upon Tyne | United Kingdom | NE1 4LP | |
| 39 | Nottingham University Hospitals NHS Trust | Nottingham | United Kingdom | NG7 2UH | |
| 40 | Sheffield Children's Hospital | Sheffield | United Kingdom | S1 0 2TH |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR109101
- 2020-005503-40
- CNTO1275JPA3001