Guselkumab for Ulcerative Colitis

(ASTRO Trial)

Recruiting at 342 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: Prohibited medications

Disqualifiers: Crohn's disease, Surgery, COVID-19, 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

418 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests an injectable medication called guselkumab on people with severe ulcerative colitis. It aims to see if blocking a protein that causes inflammation can help these patients achieve remission.

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

The trial information mentions that participants cannot be receiving prohibited medications and treatments, but it does not specify which ones. It's best to discuss your current medications with the trial team to see if any need to be stopped.

What data supports the effectiveness of the drug Guselkumab for treating ulcerative colitis?

The QUASAR Phase 2b Induction Study showed that Guselkumab, which targets a specific part of the immune system, was effective in patients with moderate to severe ulcerative colitis who did not respond well to other treatments. ^{1 2 3 4 5}

Is guselkumab safe for humans?

The QUASAR Phase 2b study looked at the safety of guselkumab in people with ulcerative colitis and found it to be generally safe for use in humans. ^{4 6 7 8 9}

How is the drug guselkumab different from other treatments for ulcerative colitis?

Guselkumab is unique because it targets the interleukin-23p19 subunit, which is a different mechanism compared to other treatments for ulcerative colitis. It is also administered as a subcutaneous injection, which may be more convenient for some patients compared to intravenous treatments. ^{4 5 10 11 12}

Research Team

Janssen Research & Development, LLC Clinical trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with moderately to severely active ulcerative colitis who haven't responded well to or can't tolerate standard treatments. They must have been diagnosed at least 12 weeks before the study starts and cannot be on certain medications, have recent or upcoming surgery that could affect results, just rectal UC, other types of colitis, Crohn's disease, or an active COVID-19 infection.

Inclusion Criteria

Signed informed consent form

I am 18 years old or older.

My ulcerative colitis is moderate to severe according to the Mayo score.

Exclusion Criteria

I currently have a severe case of COVID-19.

My ulcerative colitis affects only my rectum.

I haven't had surgery in the last 8 weeks and don't plan to during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive guselkumab or placebo subcutaneous injections to evaluate efficacy and clinical remission

12 weeks

Extended Treatment

Continued treatment to assess long-term efficacy and safety, including endoscopic and symptomatic improvements

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events

Up to 268 weeks

Treatment Details

Interventions

• Guselkumab

Trial Overview The trial is testing three different doses of a medication called Guselkumab against a placebo in people with ulcerative colitis. The main goal is to see if Guselkumab helps patients achieve clinical remission better than no treatment (placebo).

Participant Groups

Group I: Group 2: Guselkumab Experimental Treatment 2 Interventions

Participants will receive guselkumab (Dose 1) SC injection followed by guselkumab (Dose 3) SC injection.

Group II: Group 1: Guselkumab Experimental Treatment 2 Interventions

Participants will receive guselkumab (Dose 1) subcutaneous (SC) injection followed by guselkumab (Dose 2) SC injection.

Group III: Group 3: Placebo Placebo Group 1 Intervention

Participants will receive matching placebo SC injection.

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+

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

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]

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]

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]

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 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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[A retrospective analysis of azathioprine in the treatment of 24 patients with refractory ulcerative colitis]. [2014]

2. England pubmed.ncbi.nlm.nih.gov

Anti-CD3 antibody visilizumab is not effective in patients with intravenous corticosteroid-refractory ulcerative colitis. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Treatment efficacy and safety of low-dose azathioprine in chronic active ulcerative colitis patients: A meta-analysis and systemic review. [2023]

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

Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study. [2023]

5. Netherlands 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. [2023]

6. United States 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Positioning Tofacitinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis. [2019]

8. United States 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Is tofacitinib a game-changing drug for ulcerative colitis? [2021]

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

Guselkumab for the Treatment of Crohn's Disease: Induction Results From the Phase 2 GALAXI-1 Study. [2023]

11. Spain pubmed.ncbi.nlm.nih.gov

Infliximab-induced psoriasis in an ulcerative colitis patient successfully treated with guselkumab. [2023]

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

Guselkumab: First Global Approval. [2019]