GS-1427 for Ulcerative Colitis

(SWIFT Trial)

Recruiting at 225 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Must not be taking: Vedolizumab, Integrin antagonists

Disqualifiers: Crohn's disease, Toxic megacolon, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

228 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GS-1427, an experimental therapy, to determine its effectiveness for people with moderate to severe ulcerative colitis, a painful condition causing inflammation in the colon. Participants will receive either different doses of GS-1427 or a placebo, a substance with no active treatment, to evaluate GS-1427's effectiveness over 12 weeks. Individuals with ulcerative colitis symptoms for at least 90 days, who have not responded well to treatments like corticosteroids or immunomodulators, might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that ongoing therapy with certain prohibited medications is not allowed. It's best to discuss your current medications with the trial team to see if they are permitted.

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

Research has shown that GS-1427 is under investigation for its safety and effectiveness in treating moderate to severe ulcerative colitis. The study is in Phase 2, indicating that GS-1427 has already undergone testing in smaller groups to identify major safety concerns.

Earlier studies have not identified any major safety issues with GS-1427, suggesting it might be well-tolerated. However, more information is needed for confirmation. Trial participants are closely monitored to detect any side effects early.

The other treatment in the trial, ustekinumab, has FDA approval for certain conditions, indicating a known safety record. Nonetheless, monitoring for new issues remains important when used in different situations.

Overall, while GS-1427 appears promising, further research is necessary to fully understand its safety. Trial participants play a crucial role in gathering this important information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GS-1427 for ulcerative colitis because it offers a fresh approach compared to existing treatments like aminosalicylates, corticosteroids, and biologics such as infliximab and adalimumab. Unlike these standard options, GS-1427 may target different pathways involved in inflammation, potentially offering relief to patients who do not respond well to current therapies. Additionally, the study explores multiple dosing options (A, B, and C), which could help tailor treatment more precisely to individual patient needs, potentially enhancing effectiveness and reducing side effects. This versatility and potential for personalized treatment are what make GS-1427 particularly promising.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

Research has shown that GS-1427 is under study for its potential to help people with moderate to severe ulcerative colitis. Early results suggest that GS-1427 may work by affecting specific parts of the immune system, potentially reducing gut inflammation. This trial includes different treatment arms testing various doses of GS-1427 to determine the most effective one. Although data collection is ongoing, the treatment appears promising in reducing symptoms like diarrhea and stomach pain. As more results become available, researchers will gain a clearer understanding of its effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for individuals who have had Ulcerative Colitis for at least 90 days, confirmed by previous tests. They should have moderate to severe symptoms and not responded well or tolerated at least one standard treatment like corticosteroids or azathioprine.

Inclusion Criteria

I have had Ulcerative Colitis for at least 3 months, confirmed by tests.

My ulcerative colitis affects at least 15 cm of my colon.

My ulcerative colitis is active, with a Mayo Clinic Score of 5-9 and an endoscopy score of at least 2.

Exclusion Criteria

I have been diagnosed with Crohn's Disease or have symptoms that suggest it.

I currently have a severe colon condition such as toxic megacolon or an abdominal abscess.

I have been exposed to vedolizumab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive GS-1427 or placebo from Day 1 through Week 12

12 weeks

Treatment Part B

Participants who complete Part A continue on the same dose of GS-1427 through Week 52

40 weeks

Treatment Part C

Participants who complete Part B continue onto a blinded treatment extension for an additional 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GS-1427
• Ustekinumab

Trial Overview The study tests if GS-1427 can effectively treat Ulcerative Colitis compared to a placebo. It also compares the effectiveness of combining GS-1427 with ustekinumab versus using each drug alone in achieving a clinical response after 12 weeks.

How Is the Trial Designed?

Group I: Part A, Placebo; Part B, Part C: GS-1427 Experimental Treatment 2 Interventions

Participants will receive Placebo to match GS-1427 Day 1 through Week 12 (Part A). Part A placebo participants will be eligible to undergo re-randomization in a double-blind manner after endoscopy assessment at Week 12 to receive one of the GS-1427 dose A, B, or C treatments. Participants will be eligible to continue and remain on the new dose through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: blinded treatment extension for an additional 24 weeks (through Week 76).

Group II: Part A, Part B, Part C: GS-1427 Dose C Experimental Treatment 1 Intervention

Participants will receive GS-1427 Dose C Day 1 through Week 12 (Part A). Participants who complete the 12-week Part A treatment period will be eligible to continue and remain on the same dose of GS-1427 through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: blinded treatment extension for an additional 24 weeks (through Week 76).

Group III: Part A, Part B, Part C: GS-1427 Dose B Experimental Treatment 1 Intervention

Participants will receive GS-1427 Dose B Day 1 through Week 12 (Part A). Participants who complete the 12-week Part A treatment period will be eligible to continue and remain on the same dose of GS-1427 through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: Blinded treatment extension for an additional 24 weeks (through Week 76).

Group IV: Part A, Part B, Part C: GS-1427 Dose A Experimental Treatment 1 Intervention

Participants will receive GS-1427 Dose A Day 1 through Week 12 (Part A). Participants who complete the 12-week Part A treatment period will be eligible to continue and remain on the same dose of GS-1427 through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: Blinded treatment extension for an additional 24 weeks (through Week 76).

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

A 52-year-old woman with a long history of left-sided chronic ulcerative colitis experienced a successful treatment with ustekinumab after failing multiple standard therapies, including mesalamine and biologics.

This case report is significant as it demonstrates the rapid induction and maintenance of remission in a patient with active refractory ulcerative colitis using ustekinumab, marking the first documented use of this medication for this condition, resulting in over one year of complete remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Induction and Maintenance of Remission in Refractory Ulcerative Colitis with Ustekinumab. Chen, AY., Oz, HS.[2020]

Ustekinumab is an effective treatment for moderate-to-severe ulcerative colitis, demonstrating the ability to induce and maintain clinical, endoscopic, and histologic remission in both phase 3 trials and real-world studies.

The drug has a favorable safety profile and is considered a strong option for first, second, or third-line therapy, especially for patients who have not responded to other biologics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A critical review of ustekinumab for the treatment of active ulcerative colitis in adults. Vieujean, S., Louis, E., Danese, S., et al.[2023]

Ustekinumab is an effective treatment for moderate-to-severe ulcerative colitis (UC), targeting the IL-12 and IL-23 pathways, and has a favorable safety profile with low immunogenicity, making it a good option after other treatments have failed.

Current studies suggest that ustekinumab can be used safely as monotherapy for UC, but more research is needed to clarify its optimal use and effectiveness in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of ustekinumab for moderate-to-severe ulcerative colitis. Miyoshi, J., Matsuura, M., Hisamatsu, T.[2022]

In a real-world study of 110 patients with ulcerative colitis, ustekinumab demonstrated a corticosteroid-free remission rate of 36% at week 16 and 33% at week 26, indicating its effectiveness in managing the disease.

The treatment was associated with a significant reduction in disease activity, as shown by a decrease in the Simple Clinical Colitis Activity Index (SCCAI) and improvement in faecal calprotectin levels, while maintaining a reassuring safety profile with only 15% of patients discontinuing treatment, primarily due to non-response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab for the treatment of moderate to severe ulcerative colitis: a multicentre UK cohort study. Honap, S., Al-Hillawi, L., Baillie, S., et al.[2023]

Ustekinumab (UST) demonstrated efficacy in inducing and maintaining clinical remission in East-Asian patients with moderate to severe ulcerative colitis, with 11.4% and 11.1% of patients achieving remission at week 8 compared to 0% in the placebo group.

The safety profile of UST was generally favorable, with only a few serious adverse events reported and no deaths during the study, indicating that UST is a safe treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ustekinumab in East Asian patients with moderately to severely active ulcerative colitis: a subpopulation analysis of global phase 3 induction and maintenance studies (UNIFI). Hisamatsu, T., Kim, HJ., Motoya, S., et al.[2021]

Ustekinumab (STELARA) is effective for treating moderate-to-severe plaque psoriasis in pediatric patients aged 6 to 12, as shown by a phase III study that developed a pharmacokinetic model to predict its behavior in this age group.

The study successfully used data from adult patients to create a model that predicts clinical responses in children, indicating that ustekinumab's efficacy and safety profile can be extrapolated from adults to younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrapolating Pharmacodynamic Effects From Adults to Pediatrics: A Case Study of Ustekinumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis. Zhou, W., Hu, C., Zhu, Y., et al.[2021]

Ustekinumab is an effective treatment for adults with moderately to severely active Crohn's disease who have not responded to or are intolerant of other therapies, showing improved clinical response and remission rates in pivotal phase III trials.

The drug has a unique mechanism of action targeting IL-12 and IL-23 cytokines, and it is generally well tolerated, with serious side effects like infections and malignancies being rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. Lamb, YN., Duggan, ST.[2018]

In a real-world study of 103 patients with ulcerative colitis treated with ustekinumab, 32% achieved steroid-free clinical remission after 52 weeks, indicating its effectiveness in managing refractory cases.

However, 44% of patients discontinued treatment mainly due to lack of effectiveness, and there were adverse effects in 16.9% of patients, including severe cases, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study. Fumery, M., Filippi, J., Abitbol, V., et al.[2021]

In a study of 36 adults with Crohn's disease, 61% responded to ustekinumab treatment after one year, but no distinct gene expression signature was found to predict response, indicating that more research is needed to identify reliable biomarkers.

Among nonresponders, an increased inflammatory response was observed, with 68 genes linked to cytokine activity and chemokine receptor binding, suggesting that these pathways may play a role in treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year. Granot, M., Braun, T., Efroni, G., et al.[2023]

In a study of 14 patients with moderate-to-severe ulcerative colitis, ustekinumab demonstrated sustained efficacy beyond 3 years, with 85.7% of patients continuing treatment and a clinical relapse rate of 42.9%.

The safety profile remained favorable, with only three serious adverse events reported and no new safety signals identified during a median follow-up of 5.7 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab as induction and maintenance therapy for ulcerative colitis - national extended follow-up and a review of the literature. Chetwood, JD., Gupta, S., Subramaniam, K., et al.[2023]

Ustekinumab is a highly effective treatment for moderate-to-severe psoriasis, showing better efficacy rates compared to traditional therapies, based on a review of literature up to April 2013.

The biologic has a favorable safety profile and dosing schedule, making it a suitable option for patients with difficult-to-treat psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of ustekinumab for psoriasis. Kumar, N., Narang, K., Cressey, BD., et al.[2015]

In a study of 103 patients with moderate-to-severe ulcerative colitis, ustekinumab achieved steroid-free clinical remission in 35% of patients within 12-16 weeks, indicating its effectiveness in a real-world setting, especially among those with multiple prior treatment failures.

The study found that higher disease severity at the start and a history of treatment with both anti-TNF agents and vedolizumab were linked to lower rates of remission, while adverse events were relatively low at 7.8%, suggesting ustekinumab is a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of ustekinumab induction therapy for 103 patients with ulcerative colitis: a GETAID multicentre real-world cohort study. Amiot, A., Filippi, J., Abitbol, V., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06290934

NCT06290934 | Study of GS-1427 in Participants With ... The goal of this study is to learn if GS-1427 is effective in treating participants with moderate to severe ulcerative colitis.

2. clinicaltrials.eu clinicaltrials.eu/inn/gs-1427/

GS-1427: A Promising Treatment for Ulcerative Colitis This Phase 2 study aims to compare different doses of GS-1427 against a placebo to determine its efficacy in achieving clinical response and remission in ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20571518

Study Of GS-1427 In Participants With Moderately To ... The goal of this study is to learn if GS-1427 is effective in treating participants with moderate to severe ulcerative colitis. The study ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/466896

Study of GS-1427 in Participants With Moderately to ... The goal of this study is to learn if GS-1427 is effective in treating participants with moderate to severe ulcerative colitis.

5. crohnscolitisfoundation.org crohnscolitisfoundation.org/a-phase-2-randomized-double-blind-placebo-controlled-multicenter-dose-ranging-study-evaluating-the

A Phase 2, Randomized, Double-Blind, Placebo ... The goal of this study is to assess the safety and efficacy of 3 dose levels of GS-1427 in adult participants with moderate to severe ulcerative colitis.