Study of GS-1427 in Participants With Moderately to Severely Active UC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

10 Sep 2024 → ongoing

Decision date (initial)

2024-07-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc.

External identifiers

EU CT number

2023-508304-38-00

ClinicalTrials.gov

NCT06290934

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the efficacy of GS 1427, compared with placebo control, in achieving clinical response at Week 12

Secondary objectives 7

1. To evaluate the safety and tolerability of GS-1427 up to Week 116
2. To assess the efficacy of GS-1427 in achieving clinical remission at Week 12
3. To assess the efficacy of GS-1427 in achieving clinical remission at Week 52
4. To assess the efficacy of GS-1427, compared with placebo control, in achieving histologic-endoscopic mucosal improvement at Week 12
5. To assess the efficacy of GS-1427, compared with placebo control, in achieving mucosal healing at Week 12
6. To assess the efficacy of GS-1427, compared with placebo control, in achieving endoscopic improvement at Week 12
7. To assess the efficacy of GS-1427 in achieving partial mMCS remission at Week 52

Conditions and MedDRA coding

Ulcerative Colitis (UC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participants have UC with symptoms of at least 90 days duration before randomization, with the diagnosis confirmed by endoscopy and histology at any time prior to randomization. Documentation of endoscopy and histology consistent with the diagnosis of UC must be available in the source documents.
2. Participants have UC with minimum disease extent of 15 cm from the anal verge.
3. Participants have moderately to severely active UC as determined by endoscopy occurring during screening with a total mMCS of 5 to 9 points, including a centrally read endoscopic subscore of at least 2.
4. Participants have an inadequate response or loss of response or are intolerant to at least 1 of the following UC treatments:  Corticosteroids  Immunomodulators: azathioprine, 6-mercaptopurine, or 6-thioguanine (see full inclusion criteria for details)  Advanced therapy: have an inadequate response or loss of response or are intolerant to an advanced therapy (AT) for the treatment of UC: ○ Tumor necrosis factor-alpha (TNF-α) inhibitor: eg, infliximab, adalimumab, golimumab, or biosimilars ○ Interleukin-12/23 inhibitor: eg, Ustekinumab. Sphingosine 1-phosphate receptor modulator: eg, ozanimod ○ Janus kinase inhibitor: eg, tofacitinib, upadacitinib, filgotinib
5. Participants have an inadequate response or loss of response or are intolerant to < 3 AT mechanisms of action for UC (use of 2 or more AT with the same mechanism of action, eg, 2 TNF-α inhibitors, counts as 1 mechanism of action):

Exclusion criteria 5

1. Have a current diagnosis of Crohn’s disease (CD) or clinical findings suggestive of CD, diagnosis of indeterminate colitis due to causes such as an enteric pathogen, or lymphocytic or collagenous colitis.
2. Have a current diagnosis of toxic megacolon, symptomatic colonic stricture, acute severe colitis, fulminant colitis, or abdominal abscess at screening or randomization.
3. Have any history of exposure to vedolizumab or other integrin antagonists.
4. Have any history of stroke, seizure disorder, multiple sclerosis, neurodegenerative disease of brain (such as Parkinson’s disease, dementias), or brain tumor.
5. Have a positive progressive multifocal leukoencephalopathy subjective checklist at screening or at randomization prior to the administration of the first dose of study drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical response at Week 12 Clinical response is defined as a decrease from baseline in the modified Mayo Clinic Score (mMCS) of ≥ 2 points and at least a 30% reduction from baseline, and a decrease in rectal bleeding subscore of ≥ 1 from baseline or an absolute rectal bleeding subscore of 0 or 1.

Secondary endpoints 7

1. Incidence of treatment-emergent adverse events, serious adverse events, or deaths, and treatment-emergent laboratory abnormalities
2. Clinical remission at Week 12
3. Clinical remission at Week 52 Clinical remission is defined as an mMCS of ≤ 2 points, including a stool frequency subscore (SFS) ≤ 1 and not greater than baseline, rectal bleeding subscore of 0, and centrally-read endoscopic subscore ≤ 1 (score of 1 modified to exclude friability).
4. Histologic-endoscopic mucosal improvement at Week 12 Histologic-endoscopic mucosal improvement is defined as a Geboes score ≤ 3.1 and endoscopic subscore of ≤ 1.
5. Mucosal healing at Week 12 Mucosal healing is defined as a Geboes score ≤ 2B.1 and endoscopic subscore ≤ 1.
6. Endoscopic improvement at Week 12 Endoscopic improvement is defined as an endoscopic subscore ≤ 1.
7. Partial mMCS remission at Week 52 Partial mMCS remission is defined as a SFS ≤ 1 and rectal bleeding subscore of 0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 7

Locations

10 EU/EEA countries · 46 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 153 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications