GS-1427 for Ulcerative Colitis

(SWIFT Trial)

Recruiting at 141 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

Trial Summary

What is the purpose of this trial?

The goal of this study is to learn if GS-1427 is effective in treating participants with moderate to severe ulcerative colitis. The study will compare participants in different treatment groups treated with GS-1427 with participants treated with placebo. The primary objective of this study is to assess the efficacy of GS-1427, compared with placebo control, in achieving clinical response at Week 12.

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.

What data supports the effectiveness of the drug GS-1427 for treating ulcerative colitis?

Ustekinumab, a component of the treatment, has been shown to help some patients with ulcerative colitis achieve remission, meaning their symptoms improve significantly. In one case, a patient with severe ulcerative colitis who did not respond to other treatments experienced complete remission for over a year after using ustekinumab. ^{1 2 3 4 5}

Is ustekinumab safe for humans?

Ustekinumab has been shown to be generally safe in clinical trials for ulcerative colitis, with low rates of adverse events (unwanted side effects) reported in studies lasting up to 3 years. ^{2 6 7 8 9}

How is the drug GS-1427 (Ustekinumab) different from other treatments for ulcerative colitis?

GS-1427, also known as Ustekinumab, is unique because it targets specific proteins (interleukins 12 and 23) involved in inflammation, offering a different approach compared to other treatments that may target different pathways. It is used for patients who have not responded well to conventional therapies, providing an alternative option for those with moderate-to-severe ulcerative colitis. ^{1 4 10 11 12}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 (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 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]

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 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]

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. Korea (South) 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). [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Rapid Induction and Maintenance of Remission in Refractory Ulcerative Colitis with Ustekinumab. [2020]

4. United States 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

A critical review of ustekinumab for the treatment of active ulcerative colitis in adults. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study. [2021]

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

Ustekinumab as induction and maintenance therapy for ulcerative colitis - national extended follow-up and a review of the literature. [2023]

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

Ustekinumab for the treatment of moderate to severe ulcerative colitis: a multicentre UK cohort study. [2023]

9. England 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. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Long-term safety of ustekinumab for psoriasis. [2015]

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

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of ustekinumab for moderate-to-severe ulcerative colitis. [2022]