Ustekinumab/Guselkumab for Juvenile Psoriatic Arthritis

(PSUMMIT-Jr Trial)

Recruiting in Palo Alto (17 mi)

+64 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Janssen Research & Development, LLC

Must be taking: Methotrexate, Sulfasalazine

Disqualifiers: Enthesitis-related arthritis, Tuberculosis, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial allows you to continue taking methotrexate, sulfasalazine, leflunomide, oral corticosteroids, or NSAIDs, but you must be on a stable dose. If you have used certain other medications like anti-TNFα agents, IL-17 inhibitors, or JAK inhibitors, a washout period (time without taking these medications) is required.

What data supports the effectiveness of the drug Guselkumab for treating juvenile psoriatic arthritis?

Guselkumab has been shown to improve clinical outcomes in patients with psoriatic arthritis, as seen in studies where it was effective in both biologic-naive patients and those with prior treatment experience. Additionally, it has been effective in treating moderate to severe plaque psoriasis, suggesting potential benefits for similar inflammatory conditions. ^{1 2 3 4 5}

Is Ustekinumab/Guselkumab safe for use in humans?

Guselkumab and Ustekinumab have been generally well tolerated in studies for conditions like plaque psoriasis and psoriatic arthritis, with serious infections or major heart-related issues occurring rarely. These treatments have been used in adults and have shown a good safety profile, but more data is needed for their use in children. ^{1 2 3 6 7}

How is the drug Ustekinumab/Guselkumab unique for treating juvenile psoriatic arthritis?

Ustekinumab and Guselkumab are unique because they target specific proteins in the immune system, interleukins IL-12, IL-23, and IL-17, which are involved in inflammation. This makes them different from traditional treatments like TNF inhibitors, offering an alternative for patients who do not respond well to other therapies. ^{2 7 8 9 10}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for children with active juvenile psoriatic arthritis who've had it for at least 3 months. They must be up-to-date on immunizations and have tried other treatments without success. Kids can't join if they have a different type of arthritis, serious infections like TB, or hepatitis C.

Inclusion Criteria

I was diagnosed with juvenile psoriatic arthritis more than 3 months ago, not enthesitis-related arthritis.

I have active arthritis in 3 or more joints.

I have used certain medications for my condition, following a break period.

Exclusion Criteria

I had a shingles infection within the last 8 weeks.

I have arthritis that affects where my tendons or ligaments meet my bones.

I have had TB or fungal infections like histoplasmosis or coccidioidomycosis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weight-based doses of ustekinumab or guselkumab subcutaneously, with dosing intervals based on cohort and risk of joint damage

52 weeks

Visits at Weeks 0, 4, and then every 4, 8, or 12 weeks depending on cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Treatment Details

Interventions

• Guselkumab (Monoclonal Antibodies)
• Ustekinumab (Monoclonal Antibodies)

Trial Overview The study tests Ustekinumab and Guselkumab's effects on juvenile psoriatic arthritis. It looks at how the body processes these drugs, their safety, effectiveness, and whether the body develops resistance to them.

Participant Groups

Group I: Cohort 2: Guselkumab Experimental Treatment 1 Intervention

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.

Group II: Cohort 1: Ustekinumab Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Guselkumab is an effective treatment for moderate to severe plaque psoriasis, showing superior results compared to placebo and adalimumab in the VOYAGE trials, with benefits maintained for up to 2 years.

Patients who previously did not respond well to ustekinumab showed significantly better outcomes when switched to guselkumab, indicating its efficacy in treatment-resistant cases, while also improving overall quality of life and being well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab: A Review in Moderate to Severe Plaque Psoriasis. Al-Salama, ZT., Scott, LJ.[2019]

Guselkumab is an approved treatment for moderate-to-severe plaque psoriasis, specifically designed to inhibit interleukin 23 (IL-23), which plays a key role in the inflammatory process of the disease.

By blocking IL-23 from binding to its receptor, guselkumab disrupts the IL-17 pathway, which is crucial for the activation of type 17 helper T cells, thereby reducing inflammation and symptoms in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab: First Global Approval. Markham, A.[2019]

Guselkumab (GUS) demonstrated a favorable safety profile in patients with psoriatic arthritis (PsA), showing low adverse event (AE) rates for both TNFi-naïve (139.7/100 patient-years) and TNFi-experienced patients (174.0/100 patient-years) over a period of up to 2 years.

The safety outcomes, including rates of serious AEs and treatment discontinuation, were consistent between GUS-treated patients and those receiving placebo, indicating that GUS is a safe treatment option for PsA regardless of prior TNFi use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Guselkumab With and Without Prior Tumor Necrosis Factor Inhibitor Treatment: Pooled Results Across 4 Studies in Patients With Psoriatic Arthritis. Rahman, P., Boehncke, WH., Mease, PJ., et al.[2023]

In a study of 114 patients with active psoriatic arthritis (PsA) who started on guselkumab, 78.9% continued treatment after 6 months, showing strong treatment persistence.

Patients experienced significant improvements in joint and skin symptoms, with a mean reduction in disease activity index (cDAPSA) of -5.4 and notable decreases in pain and psoriasis severity, confirming guselkumab's efficacy in a real-world setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. Mease, PJ., Ogdie, A., Tesser, J., et al.[2023]

In the DISCOVER-2 trial, guselkumab was tested in biologic-naive patients with active psoriatic arthritis, demonstrating significant efficacy in reducing disease activity compared to placebo.

The study's double-blind, randomized, placebo-controlled design ensures robust results, highlighting guselkumab as a promising treatment option for patients who have not previously received biologic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab safely improved clinical outcomes in biologic-naive patients with psoriatic arthritis. Schattner, A.[2020]

Biologic response modifiers like etanercept, adalimumab, infliximab, and ustekinumab have shown efficacy and safety in treating psoriasis in adults, but only etanercept is approved for use in children in the EU, and none are approved in the US.

Evidence from case reports and clinical trials supports the use of etanercept for treating psoriasis in children, and data from its use in other inflammatory diseases in children suggest a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic response modifiers and pediatric psoriasis. Bellodi Schmidt, F., Shah, KN.[2015]

Ustekinumab is an effective treatment for adults with active psoriatic arthritis, showing significant improvement compared to placebo in phase 3 trials, with benefits maintained up to 100 weeks.

The drug has a favorable safety profile, with rare occurrences of serious infections or major cardiovascular events, making it a valuable option for patients who do not respond to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab: a review of its use in psoriatic arthritis. McKeage, K.[2021]

Ustekinumab, an interleukin-12 and -23 antagonist, is primarily used for moderate to severe plaque psoriasis and other inflammatory conditions, but emerging literature suggests it may also be effective for various off-label uses, including other types of psoriasis and hidradenitis suppurativa.

Despite promising findings for these off-label conditions, the review highlights the need for more clinical trials to thoroughly evaluate the safety and efficacy of ustekinumab beyond its approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label uses of ustekinumab. Ye, L., Wu, Z., Li, C., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Guselkumab: A Review in Moderate to Severe Plaque Psoriasis. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Guselkumab: First Global Approval. [2019]

3. Canada pubmed.ncbi.nlm.nih.gov

Safety of Guselkumab With and Without Prior Tumor Necrosis Factor Inhibitor Treatment: Pooled Results Across 4 Studies in Patients With Psoriatic Arthritis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Guselkumab safely improved clinical outcomes in biologic-naive patients with psoriatic arthritis. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Biologic response modifiers and pediatric psoriasis. [2015]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Ustekinumab: a review of its use in psoriatic arthritis. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Off-label uses of ustekinumab. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ustekinumab in adolescents. [2023]