Guselkumab for Ulcerative Colitis

(QUASAR Trial)

Not currently recruiting at 604 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Crohn's disease, Stoma, Fistula, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called guselkumab (also known as Tremfya) to evaluate its effectiveness and safety for people with ulcerative colitis (UC), a condition that causes swelling and sores in the colon. Participants will receive either guselkumab or a placebo (a harmless substance that resembles the treatment) to compare results. The trial seeks individuals with moderately to severely active UC who haven't found success with other treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications, but it mentions that some medications might be prohibited. It's best to discuss your specific medications with the trial team.

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

Research shows that guselkumab is generally well-tolerated by people with moderate to severe ulcerative colitis, with studies finding few long-term side effects. Specifically, over 70% of patients taking guselkumab experienced significant improvement in their symptoms, known as clinical remission.

While safety data collection for ulcerative colitis continues, guselkumab has been safely used to treat Crohn's disease, another type of inflammatory bowel disease. This suggests it might also be safe for ulcerative colitis patients. Overall, evidence indicates that guselkumab is safe, with manageable side effects, though ongoing studies will continue to provide more information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ulcerative colitis?

Guselkumab is unique because it targets interleukin-23 (IL-23), a protein involved in inflammation, which is different from many current ulcerative colitis treatments that focus on tumor necrosis factor (TNF) or integrins. Researchers are excited about Guselkumab because it offers a new mechanism of action, potentially providing relief for patients who do not respond to existing therapies like TNF inhibitors or steroids. Additionally, Guselkumab can be administered both intravenously for quick induction and subcutaneously for maintenance, offering flexibility in treatment regimens.

What evidence suggests that guselkumab might be an effective treatment for ulcerative colitis?

Research has shown that guselkumab may help treat moderate to severe ulcerative colitis (UC). In earlier studies, 36.7% of patients taking guselkumab experienced major improvements, with fewer symptoms and better gut health. Guselkumab also reduced inflammation observed during a colonoscopy, achieving endoscopic remission. The treatment's benefits lasted up to 48 weeks. In this trial, participants will receive different doses of guselkumab or a placebo to further evaluate its effectiveness. These findings suggest that guselkumab could be a strong option for managing UC symptoms. ^{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 people with moderate to severe ulcerative colitis who haven't responded well to other treatments. Participants must have a confirmed diagnosis of UC and meet specific lab test requirements. Those with only rectal UC, less than 20 cm of colon affected, fistulas, or certain other bowel diseases can't join.

Inclusion Criteria

Screening laboratory test results within the parameters specified in the protocol

My ulcerative colitis is moderate to severe, based on a specific score.

I have been diagnosed with ulcerative colitis.

Exclusion Criteria

I have been diagnosed with a specific type of colitis or Crohn's disease.

I am not taking any medications or treatments that are not allowed.

My ulcerative colitis affects only my rectum or less than 20 cm of my colon.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Study 1

Participants receive guselkumab or placebo intravenously, with clinical response assessed at Week 12

12 weeks

Induction Study 2

Participants receive guselkumab or placebo intravenously, with clinical remission assessed at Week 12

12 weeks

Maintenance Study

Participants receive guselkumab or placebo subcutaneously every 4 or 8 weeks, with clinical remission assessed at Week 44

44 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Guselkumab

Trial Overview

The study is testing the effectiveness and safety of guselkumab compared to a placebo in treating ulcerative colitis. Guselkumab is given to see if it can help reduce symptoms and improve the condition of those with active UC.

How Is the Trial Designed?

Group I: Maintenance Study: Maintenance Dose Regimen 2 Experimental Treatment 1 Intervention

Participants will receive guselkumab maintenance dose regimen 2 SC every 8 weeks (q8w).

Group II: Maintenance Study: Maintenance Dose Regimen 1 Experimental Treatment 1 Intervention

Participants will receive guselkumab maintenance dose regimen 1 subcutaneously (SC) every 4 weeks (q4w).

Group III: Induction Study 2: Guselkumab IV Experimental Treatment 1 Intervention

Participants will receive guselkumab IV in Induction Study 2. Subsequent study treatment will be determined by the participant's clinical response status at Week 12.

Group IV: Induction Study 1: Guselkumab Dose 2 Experimental Treatment 1 Intervention

Participants will receive guselkumab dose 2 IV in Induction Study 1. Subsequent study treatment will be determined by the participant's clinical response status at Week 12.

Group V: Induction Study 1: Guselkumab Dose 1 Experimental Treatment 1 Intervention

Participants will receive guselkumab dose 1 intravenously (IV) in Induction Study 1. Subsequent study treatment will be determined by the participant's clinical response status at Week 12.

Group VI: Induction Study 2: Placebo IV Placebo Group 1 Intervention

Participants will receive matching placebo IV in Induction Study 2. Subsequent study treatment will be determined by the participant's clinical response status at Week 12. Clinical nonresponders will be administered guselkumab IV.

Group VII: Induction Study 1: Placebo IV Placebo Group 1 Intervention

Participants will receive matching placebo IV in Induction Study 1. Subsequent study treatment will be determined by the participant's clinical response status at Week 12. Clinical nonresponders will be administered guselkumab IV.

Group VIII: Maintenance Study: Placebo SC Placebo Group 1 Intervention

Participants will receive matching placebo SC q4w.

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

In the QUASAR Phase 2b Induction Study, guselkumab, an interleukin-23p19 antagonist, demonstrated significant efficacy in treating moderately to severely active ulcerative colitis, with 61.4% and 60.7% of patients achieving clinical response at week 12 for the 200 mg and 400 mg doses, respectively, compared to only 27.6% for placebo.

The safety profile of guselkumab was comparable to that of the placebo, indicating that it is a safe treatment option for patients who have not responded adequately to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study. Peyrin-Biroulet, L., Allegretti, JR., Rubin, DT., et al.[2023]

Tofacitinib, an oral medication that inhibits Janus kinases, has shown effectiveness in inducing and maintaining remission in adults with moderate to severe ulcerative colitis, providing a new treatment option for patients who do not respond to conventional therapies or biologics.

The review focuses on the efficacy and safety of tofacitinib based on randomized controlled trials, highlighting its potential role in the treatment strategy for ulcerative colitis, pending regulatory approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positioning Tofacitinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis. Danese, S., D'Amico, F., Bonovas, S., et al.[2019]

In a study involving 268 patients with moderate-to-severe ulcerative colitis in Japan, vedolizumab demonstrated a favorable safety profile, with a low incidence of adverse drug reactions (4.10%), including mild cases like dizziness and nausea.

Vedolizumab was effective in 84.5% of patients after three doses, showing similar therapeutic responses in both TNFα inhibitor-naïve (85.8%) and experienced patients (82.7%), indicating its potential as a reliable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Vedolizumab in Patients with Moderate-to-Severe Ulcerative Colitis: An Interim Analysis of a Japanese Post-Marketing Surveillance Study. Matsuoka, K., Hisamatsu, T., Mikami, Y., et al.[2023]

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 study of 334 ulcerative colitis patients treated with tofacitinib, approximately 35% achieved clinical remission at 12, 24, and 52 weeks, indicating its effectiveness in real-world settings.

While tofacitinib had a low incidence of serious adverse events, nearly 45% of patients lost their response after reducing the dose, highlighting the need for careful management and monitoring, especially for those with higher risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

REMIT-UC: Real-World Effectiveness and Safety of Tofacitinib for Moderate-to-Severely Active Ulcerative Colitis: A Canadian IBD Research Consortium Multicenter National Cohort Study. Ma, C., Panaccione, R., Xiao, Y., et al.[2023]

In a study involving 214 adults with moderately-to-severely active ulcerative colitis, combination therapy with guselkumab and golimumab resulted in a higher clinical response rate at week 12 (83%) compared to golimumab monotherapy (61%) and guselkumab monotherapy (75%).

The safety profile was generally acceptable, with no deaths or serious complications reported during the treatment period, although some adverse events like infections and anemia were noted, indicating the need for monitoring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial. Feagan, BG., Sands, BE., Sandborn, WJ., et al.[2023]

Tofacitinib is the first Janus kinase inhibitor approved for treating moderate-to-severely active ulcerative colitis, specifically for patients who have not responded to conventional therapies.

Despite advancements in treatment options, 25-40% of ulcerative colitis patients still do not respond to therapies, highlighting the need for effective alternatives like tofacitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is tofacitinib a game-changing drug for ulcerative colitis? Magro, F., Estevinho, MM.[2021]

Citations

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jnj.com

jnj.com/media-center/press-releases/tremfya-guselkumab-is-first-and-only-il-23-inhibitor-to-demonstrate-sustained-clinical-and-endoscopic-outcomes-with-a-fully-subcutaneous-regimen-through-48-weeks-in-ulcerative-colitis

TREMFYA® (guselkumab) is first and only IL-23 inhibitor to ...

Patients treated with subcutaneous TREMFYA® achieved clinically meaningful results in both clinical remission (36.7%) and endoscopic ...

2.

tremfyahcp.com

tremfyahcp.com/ulcerative-colitis/efficacy/

Efficacy in Moderately to Severely Active UC

Discover TREMFYA® (guselkumab) efficacy data in adults with moderately to severely active UC. See full Prescribing & Safety Information.

3.

healio.com

healio.com/news/gastroenterology/20251027/subcutaneous-guselkumab-induction-maintenance-effective-at-48-weeks-in-ulcerative-colitis

Subcutaneous guselkumab induction, maintenance ...

Subcutaneous guselkumab induction and maintenance therapy outperformed placebo in clinical and endoscopic remission at week 48.

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39800899/

Guselkumab: A New Therapeutic Option for the Treatment ...

The QUASAR findings suggest guselkumab can provide durable clinical remission and histologic normalization, addressing a significant gap in UC ...

5.

prnewswire.com

prnewswire.com/news-releases/tremfya-guselkumab-is-first-and-only-il-23-inhibitor-to-demonstrate-sustained-clinical-and-endoscopic-outcomes-with-a-fully-subcutaneous-regimen-through-48-weeks-in-ulcerative-colitis-302576330.html

TREMFYA® (guselkumab) is first and only IL-23 inhibitor ...

Patients treated with subcutaneous TREMFYA® achieved clinically meaningful results in both clinical remission (36.7%) and endoscopic ...

6.

tremfyahcp.com

tremfyahcp.com/ulcerative-colitis/safety/

Safety in Moderately to Severely Active UC

Review the TREMFYA® (guselkumab) safety profile in adults with moderately to severely active UC. See full Prescribing & Safety Information.

7.

ema.europa.eu

ema.europa.eu/en/medicines/human/EPAR/tremfya

Tremfya | European Medicines Agency (EMA)

Long-term safety data have shown that it has few side effects. For patients with moderately to severely active ulcerative colitis and Crohn's disease, the ...

8.

jnj.com

jnj.com/media-center/press-releases/tremfya-guselkumab-delivers-sustained-clinical-and-endoscopic-remission-in-ulcerative-colitis-through-two-years

TREMFYA® (guselkumab) delivers sustained clinical and ...

Data from the QUASAR long-term extension study demonstrate more than 70% of patients were in clinical remission and more than 40% of ...

9.

academic.oup.com

academic.oup.com/ecco-jcc/article/19/Supplement_1/i1205/7967516

Integrated safety analysis of phase 2 and 3 studies in Crohn's ...

While GUS has been shown to be safe in Crohn's disease (CD) and UC, safety results have only been reported in individual trials to date.

10.

tremfya.com

tremfya.com/ulcerative-colitis/results/

UC: Results & Safety

View TREMFYA ® (guselkumab) results for ulcerative colitis (UC) treatment, potential side effects, and more. See full Prescribing and Safety Information.