Subcutaneous Guselkumab for Psoriasis

(PROTOSTAR Trial)

Not currently recruiting at 50 trial locations

Overseen By Study Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: Beta blockers, Calcium channel blockers, Lithium

Disqualifiers: Nonplaque psoriasis, Chronic infections, Lymphoproliferative disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of guselkumab for children and teens with chronic plaque psoriasis, a skin condition causing itchy, red, and scaly patches. Participants will receive guselkumab (also known as Tremfya) or a placebo (a harmless, inactive substance) as an injection under the skin, while some will try etanercept, another medication. It suits children and teens aged 6 to under 18 who have had plaque psoriasis for at least 6 months and struggle to manage it with current treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking medications that cause drug-induced psoriasis, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that guselkumab is generally safe for adults with moderate-to-severe plaque psoriasis. Most participants in studies did not experience serious side effects. Common mild issues included upper respiratory infections, such as colds. This treatment has been safely used in adults for up to five years.

Etanercept, another treatment for plaque psoriasis, has a more varied safety record. It is effective but can cause serious infections in some individuals, such as tuberculosis or bacterial infections, which might require hospital care.

Both treatments have been studied in people with psoriasis. While guselkumab has a strong safety record, etanercept carries a higher risk of serious infections. Participants should consider these findings when deciding whether to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Guselkumab is unique because it targets a specific part of the immune system known as interleukin-23 (IL-23), which plays a key role in the development of psoriasis. Unlike other treatments that might broadly suppress the immune system, guselkumab offers a more targeted approach, potentially leading to fewer side effects and a more effective reduction in symptoms. Additionally, guselkumab is administered through subcutaneous injections, which may be more convenient for some patients compared to intravenous infusions or oral medications. Researchers are excited about guselkumab because it represents a new class of treatment that could transform the way psoriasis is managed, offering hope for better long-term control of the condition.

What evidence suggests that this trial's treatments could be effective for chronic plaque psoriasis?

Previous studies have shown promising results for guselkumab in treating plaque psoriasis, with about 64% of patients experiencing significant skin improvement and 90% achieving clearer skin by Week 16. In this trial, participants may receive guselkumab as part of their treatment. Similarly, etanercept, another treatment option in this trial, has proven effective, with nearly half of the patients seeing major improvement around the same time. Both treatments have greatly reduced psoriasis symptoms, offering hope to those living with this condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for children and teens aged 6 to less than 18 with chronic plaque psoriasis. They must have had the condition for at least 6 months, show certain levels of severity, be up-to-date on vaccinations or immune to varicella and MMR, and could benefit from etanercept therapy. Those with a history of lymphoproliferative disease, previous guselkumab or etanercept use, chronic infections, nonplaque psoriasis types, or drug-induced psoriasis cannot join.

Inclusion Criteria

Be otherwise healthy on the basis of physical examination, medical history, and vital signs performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator

I am immune to varicella and MMR through vaccination, past infection, or positive antibody tests.

I am eligible for light therapy or systemic treatment for plaque psoriasis.

Exclusion Criteria

I have a history of chronic or recurrent infections.

My psoriasis is not the common plaque type.

I have been treated with guselkumab or etanercept before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weight-based doses of guselkumab or placebo administered subcutaneously at specified intervals

52 weeks

Visits at Weeks 0, 4, 12, 16, 20, 24, and every 8 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long Term Extension (LTE)

Participants who are eligible and willing may continue guselkumab treatment beyond the main study period

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Etanercept
• Guselkumab
• Placebo for Guselkumab

Trial Overview The study tests the effectiveness and safety of Guselkumab administered under the skin in young patients with plaque psoriasis compared to Etanercept (another treatment) and a placebo. The goal is to see how well Guselkumab works in reducing symptoms of this skin condition.

How Is the Trial Designed?

Group I: Part 2: Guselkumab Experimental Treatment 1 Intervention

Participants will receive a weight-based dose of open-label guselkumab SC at Weeks 0, 4 and q8w thereafter through Week 52. Participants who are eligible and willing to continue guselkumab treatment, may enter the LTE of the study and continue to receive guselkumab at Week 52 and q8w thereafter.

Group II: Part 1 Group 1: Guselkumab Experimental Treatment 2 Interventions

Participants in Part 1a (age greater than or equal to (\>=) 12 - less than (\<) 18 years) will receive a weight-based dose of guselkumab subcutaneously (SC) at Weeks 0, 4, and 12. Participants who are PASI 90 responders at Week 16 will not receive any additional doses of guselkumab until they lose \>=50% of their Week 16 PASI response, then they receive 1 dose guselkumab, followed by a dose 4 weeks later, and every 8 weeks (q8w) thereafter through Week 52. Participants who are PASI 90 non-responders at Week 16 will receive a placebo injection at Week 16 and continue to receive guselkumab q8w from Week 20 through Week 52. Participants who are eligible and willing to continue guselkumab may enter the Long Term Extension (LTE) Phase of the study. Part 1b (age \>= 6 - \<12 years) will follow the same dosing and commence after Part 1a data review.

Group III: Part 1 Group 3: Etanercept Active Control 2 Interventions

Participants in Part 1a (age \>= 12 - \<18 years) will receive weight-based etanercept dose up to 50 milligram SC weekly through Week 15. Participants who elect to continue in the study will receive a weight-based guselkumab dose at Weeks 20 and 24, followed by q8w dosing thereafter through Week 48. Participants who are eligible and willing to continue guselkumab treatment, may enter the LTE phase of the study. Part 1b (age \>= 6 - \<12 years) will follow the same dosing and commence after Part 1a data review.

Group IV: Part 1 Group 2: Placebo for Guselkumab Placebo Group 2 Interventions

Participants in Part 1a (age \>= 12 - \<18 years) will receive placebo for guselkumab administered SC at Weeks 0, 4, and 12. Participants who are PASI 90 responders at Week 16 will not receive any additional doses of study intervention until they lose \>=50% of their Week 16 PASI response, at which time they will receive a weight-based guselkumab SC dose, followed by a dose 4 weeks later, and q8w thereafter through Week 52. Participants who are PASI 90 non-responders at Week 16 will receive a weight-based guselkumab dose at Weeks 16 and 20, followed by q8w dosing thereafter through Week 52. Participants who are eligible and willing to continue guselkumab treatment, may enter the LTE phase of the study. Part 1b (age \>= 6 - \<12 years) will follow the same dosing and commence after Part 1a data review.

Guselkumab is already approved in United States, European Union for the following indications:

Approved in United States as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Approved in European Union as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

In a 3-year study involving 31 patients, guselkumab significantly improved psoriasis severity, with a reduction in Psoriasis Area Severity Index (PASI) from 16.4 to 0.6 and Body Surface Area (BSA) from 33.2 to 1.9, indicating its long-term efficacy in managing plaque psoriasis.

The safety profile of guselkumab was favorable, with no serious adverse events reported, and only mild side effects like pharyngitis and headaches, which did not lead to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety of Guselkumab for Moderate to Severe Psoriasis: A 3-Year Real-Life Retrospective Study. Megna, M., Potestio, L., Fabbrocini, G., et al.[2022]

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 a human monoclonal antibody that selectively blocks IL-23, which is important in the development of psoriasis and psoriatic arthritis, and it was approved for treating active psoriatic arthritis based on data from two phase-3 studies (DISCOVER-1 and -2).

This treatment represents a new therapeutic option for patients with active psoriatic arthritis, demonstrating both efficacy and safety, and it is the first selective IL-23 inhibitor to receive FDA approval for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab: the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis in Adults. Boehncke, WH., Brembilla, NC., Nissen, MJ.[2021]

Guselkumab is an effective treatment for moderate-to-severe psoriasis, showing significant improvements in skin condition and quality of life in clinical trials, and is generally well tolerated by patients.

In head-to-head trials, guselkumab outperformed adalimumab and secukinumab in achieving higher response rates for psoriasis severity, indicating its superior efficacy in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab for the treatment of adults with moderate to severe plaque psoriasis. Puig, L.[2020]

Guselkumab demonstrated superior efficacy in treating moderate-to-severe plaque psoriasis compared to both placebo and adalimumab, with significant improvements in key measures such as the Psoriasis Area and Severity Index (PASI 75) and the Investigator's Global Assessment (IGA) scores.

The safety profile of guselkumab was comparable to that of placebo and adalimumab, showing no significant increase in adverse events or serious infections, indicating it is a well-tolerated treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the Short-Term Efficacy and Safety of Guselkumab for Moderate-to-Severe Plaque Psoriasis: Meta-Analysis of Randomized Controlled Trials. Yang, J., Wang, Z., Zhang, X.[2022]

A total of 24,312 adverse event reports related to guselkumab were identified from over 22 million reports in the FDA adverse event reporting system, indicating a significant volume of data for analysis.

The study revealed unexpected adverse events associated with guselkumab, including onychomadesis, malignant melanoma in situ, endometrial cancer, and erectile dysfunction, highlighting the need for ongoing safety monitoring and further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of guselkumab in the real world: emerging signals to target preventive strategies from the FDA adverse event reporting system. Xiang, DC., Chen, W., Fu, ZW., et al.[2023]

Citations

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Long term efficacy and safety of etanercept in the treatment ... Etanercept efficacy in PsA​​ ACR 20 was achieved by 64% and 63% of those initially assigned to either etanercept or placebo, respectively, while 44% and 49%, ...

2. enbrelpro.com enbrelpro.com/efficacy/plaque-psoriasis

Plaque Psoriasis (PsA) Efficacy | Enbrel® (etanercept) Primary Endpoint · Recapture Results Through 60 Weeks. For the 50 mg BIW dosing, 91% of the initial change in mean PASI was regained 12 weeks after retreatment ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa030409

Etanercept as Monotherapy in Patients with Psoriasis The treatment of psoriasis with etanercept led to a significant reduction in the severity of disease over a period of 24 weeks.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00078819

NCT00078819 | Etanercept (Enbrel®) in Psoriasis This study will evaluate the safety and efficacy of etanercept (Enbrel®) in children with Psoriasis.

5. amgen.com amgen.com/newsroom/press-releases/2004/04/fda-approves-enbrel-to-treat-psoriasis-new-convenient-treatment-provides-rapid-and-significant-relief-of-symptoms

FDA Approves ENBREL to Treat Psoriasis In a Phase 3 study, nearly half (46 percent) of patients receiving 50 mg twice-weekly of ENBREL achieved the primary endpoint of a 75 percent or greater ...

6. enbrelpro.com enbrelpro.com/safety/plaque-psoriasis

Plaque Psoriasis (PsO) Safety | Enbrel® (etanercept) Review the safety data on Enbrel® (etanercept) in treating moderate to severe plaque psoriasis in adult patients. See Indications and Important Safety ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/103795s5556lbl.pdf

ENBREL (etanercept) - accessdata.fda.gov SERIOUS INFECTIONS. • Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1936306/

The safety of etanercept for the treatment of plaque psoriasis The short-term safety of etanercept is well established by rigorous clinical trials in rheumatoid arthritis, psoriatic arthritis, and psoriasis (Leonardi et al ...

9. enbrel.com enbrel.com/plaque-psoriasis

Moderate to Severe Plaque Psoriasis Treatment ENBREL can cause serious side effects including: New infections or worsening of infections you already have, including tuberculosis; lymphoma and other cancers ...

10. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/enbrel

Enbrel | European Medicines Agency (EMA) Psoriasis; Arthritis ... An Analysis of Real-World Data on the Safety of Etanercept in Elderly Patients with Rheumatoid Arthritis - post-authorisation study ...