Study of GS-5290 in Participants With Moderately to Severely Active Ulcerative Colitis

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

16 Apr 2024 → ongoing

Decision date (initial)

2023-09-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To demonstrate the efficacy of GS-5290, compared to placebo control, in achieving Clinical Response at Week 12

Secondary objectives 3

1. To demonstrate the efficacy of GS-5290, compared to placebo control, in achieving Clinical Remission at Week 12
2. To demonstrate the efficacy of GS-5290, compared with placebo control, in achieving endoscopic response at Week 12
3. To demonstrate the efficacy of GS-5290, compared with placebo control, in achieving Histologic Endoscopic Mucosal Improvement at Week 12

Conditions and MedDRA coding

Ulcerative Colitis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Participants assigned male at birth, or nonpregnant, nonlactating participants assigned female at birth, 18 to 75 years of age based on the date of the screening visit.
2. UC of at least 90-day duration before randomization confirmed by endoscopy and histology at any time in the past AND a minimum disease extent of 15 cm from the anal verge. Documentation of endoscopy and histology consistent with the diagnosis of UC must be available in the source documents prior to the initiation of screening.
3. Moderately to severely active UC as determined during screening with a modified Mayo Clinic Score based on the sum of Stool Frequency, Rectal Bleeding, and Endoscopic Finding of 5 to 9 points and an endoscopic subscore of 2 to 3 (determined by central reader).
4. Previous treatment history of approved UC therapy with at least one of the following advanced therapy mechanisms of action but failure (ie, loss of response or lack of response) of no more than 3 different advanced therapy mechanisms of action. a. TNFα inhibitor (eg, infliximab, adalimumab, golimumab, or approved biosimilars) b. IL-12/23 inhibitor (eg, ustekinumab or approved biosimilar) c. Leukocyte trafficking modulator (eg, vedolizumab, ozanimod, or approved biosimilar/generic) d. Janus kinase inhibitor (eg, tofacitinib, filgotinib, upadacitinib, or approved generic) e. IL-23 inhibitor (eg, risankizumab or approved biosimilar)
5. Must have the ability to understand and sign a written informed consent form.
6. May be receiving concomitant therapy for UC at the time of enrollment as specified in Section 5.6, provided the dose prescribed has been stable as indicated prior to randomization.
7. A surveillance colonoscopy for dysplasia is required prior to randomization if indicated by regional guidelines for patients with UC.
8. Meet the following tuberculosis (TB) screening criteria: a. No evidence of active TB, latent TB, or inadequately treated TB as evidenced by 1 of the following: i. A negative QuantiFERON test or equivalent assay reported by the central laboratory at screening or within 90 days prior to randomization for participants re-screening. OR ii. A history of fully treated active or latent TB according to local standard of care. Investigator must verify adequate previous anti-TB treatment and provide documentation; these participants do not require QuantiFERON testing and eligibility must be approved by the sponsor prior to enrollment in the study. AND b. A chest radiograph (views as per local guidelines with the report or films available for investigator review) taken at screening or within the 4 months prior to randomization without evidence of active or latent TB infection.
9. Laboratory assessments at screening, including baseline hematology and chemistry at Day −5 to Day −3), within the following parameters: a. Aspartate aminotransferase (AST) and, alanine aminotransferase (ALT), and total bilirubin ≤ 2 ×× upper limit of normal (ULN) b. Estimated glomerular filtration rate ≥ 60 mL/min (1.0 mL/sec) as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) {Inker 2012} cystatin C formula as described in Section 6.3.9.2. c. Hemoglobin ≥ 8 g/dL (≥ 80 g/L) d. Absolute neutrophil count ≥ 1.5 × 103/μL (≥ 1.5 GI/L) e. Platelets ≥ 100 × 103/μL (≥ 100 GI/L) f. White blood cells ≥ 3 × 103/μL (≥ 3 GI/L) g. Absolute lymphocyte count ≥ 0.75 × 103/μL (≥ 0.75 GI/L)
10. Stool sample test result negative for enteric pathogens.
11. Stool sample test result negative for ova and parasites unless approved by the medical monitor.
12. Negative human immunodeficiency virus (HIV) antibody test.
13. Negative hepatitis B virus (HBV) surface antigen test. Participants with negative hepatitis B virus surface antigen (HBsAg) test and positive hepatitis B virus core antibody (HBcAb) test must have an HBV DNA less than the lower limit of quantification (LLOQ).
14. Negative hepatitis C virus (HCV) antibody test or HCV RNA less than the LLOQ as described in Section 6.3.9.6.
15. Negative urine drug screen result. A positive drug screen will exclude participants unless it can be explained by the use of a medication (prescription or nonprescription) that is being used under the direction of a physician. Cocaine use is exclusionary.
16. Participants assigned female at birth of childbearing potential (as defined in Appendix 11.3) must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result on Day 1 prior to randomization.
17. Participants assigned male at birth and participants assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 11.3. Note: other protocol-defined inclusion criteria may apply.

Exclusion criteria 26

1. Current diagnosis of CD or diagnosis of indeterminate colitis due to an enteric pathogen, lymphocytic or collagenous colitis.
2. Participants with disease limited to the rectum (ulcerative proctitis) during screening endoscopy.
3. Participants assigned female at birth who are pregnant, breastfeeding, intend to become pregnant, or are of childbearing potential and not using an adequate contraceptive method as described in Appendix 11.3.
4. Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
5. Participants susceptible to hyperbilirubinemia as determined by UGT1A1 genotyping.
6. Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.6.2.
7. Prior surgery for UC.
8. Participants who are likely to require any type of major surgery during the study. Cataract surgery, breast surgery without reconstruction, laparoscopic cholecystectomy, laparoscopic tubal ligation and most cutaneous, superficial, dermatologic, gastrointestinal endoscopic and arthroscopic procedures can be considered minor surgeries.
9. Have had any major surgery or trauma within 8 weeks prior to randomization.
10. History or evidence of incompletely resected colonic mucosal dysplasia.
11. History of malignancy in the last 5 years except for participants who have been treated or resected for either nonmelanoma skin cancer or cervical carcinoma in situ.
12. History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma.
13. Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) or psychiatric problem (including, but not limited to alcohol or drug abuse) that, in the opinion of the investigator or sponsor, would make the participant unsuitable for the study or would prevent compliance with the study protocol.
14. History of immunodeficiency syndrome.
15. Have a stoma or ileoanal pouch.
16. Dependence on total parenteral nutrition.
17. Have a transplanted organ with exception of a corneal transplant.
18. Active clinically significant infection, or any infection requiring hospitalization or treatment with intravenous anti-infectives within 8 weeks of randomization; or any infection requiring oral anti-infective therapy within 6 weeks of randomization.
19. History of opportunistic infection.
20. History of symptomatic herpes zoster within 16 weeks of randomization, or any history of disseminated herpes simplex, disseminated herpes zoster, ophthalmic zoster, or Varicella Zoster virus central nervous system infections.
21. Currently on any chronic systemic (oral or intravenous) anti-infective therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes zoster, or atypical mycobacteria).
22. Current diagnosis of acute severe colitis, fulminant colitis, or toxic megacolon.
23. Administration of a live or attenuated vaccine within 4 weeks of randomization (Section 5.7).
24. Participants assigned female at birth who may wish to become pregnant and/or plan to undergo egg donation or egg harvesting for the purpose of current or future fertilization during the course of the study and up to 7 days after last dose of the study drug.
25. Participants assigned male at birth unwilling to refrain from sperm donation for at least 7 days after last dose of the study drug.
26. Established or suspected diagnosis of primary sclerosing cholangitis. Note: other protocol-defined exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical Response, defined as a decrease from baseline of ≥ 2 points and at least 30% in 3 components of the modified Mayo Clinic Score (MCS), Stool Frequency, Rectal Bleeding, and Endoscopic Findings, in addition to a ≥ 1 point decrease from baseline in the Rectal Bleeding subscore or Rectal Bleeding subscore of ≤ 1 at Week 12

Secondary endpoints 3

1. Clinical Remission, defined as a Stool Frequency subscore ≤ 1 and not greater than baseline, Rectal Bleeding subscore of 0, and Endoscopic Findings subscore ≤ 1 at Week 12
2. Endoscopic Response, defined as an Endoscopic Findings subscore ≤ 1 at Week 12
3. Histologic Endoscopic Mucosal Improvement, defined as an Endoscopic Findings subscore ≤ 1 and Geboes score < 3.1 (indicating neutrophil infiltration in < 5% of crypts, no crypt destruction and no erosions, ulcerations, or granulation tissue) at Week 12

Investigational products

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

Test 2

Placebo 2

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 Clinical Trials Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU Clinical Trials Support

Third parties 12

Locations

7 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 98 files

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

Application history

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