A Study to Assess the Effectiveness and Safety of RO7790121 for Induction Therapy in Participants with Moderately to Severely Active Ulcerative Colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune System Phenomena [G13], Diseases [C] - Digestive System Diseases [C06]

Trial duration

9 Jan 2025 → ongoing

Decision date (initial)

2024-11-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of afimkibart compared with placebo in inducing clinical remission

Secondary objectives 5

1. To evaluate the efficacy of afimkibart compared with placebo in inducing response
2. To evaluate the efficacy of afimkibart compared with placebo in biomarker-defined subpopulations of participants
3. To evaluate the efficacy of afimkibart compared with placebo in terms of UC-related symptoms and health-related quality of life
4. To evaluate the efficacy of afimkibart compared with placebo in terms of the participant's global impressions
5. To evaluate the safety of afimkibart compared with placebo

Conditions and MedDRA coding

Moderately to Severely Active Ulcerative Colitis (UC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 18 to ≤ 80 years at the time of signing Informed Consent Form, with bodyweight ≥ 40 kg.
2. Confirmed UC diagnosis, active UC with moderately to severely active disease confirmed by endoscopy (flexible sigmoidoscopy or colonoscopy), and active UC confirmed by endoscopy
3. Moderately to severely active UC
4. Screening for colorectal cancer (CRC) for all participants (performed according to local standards)
5. Inadequate response, loss of response, and/or intolerance to prior conventional therapy (aminosalicylates, corticosteroids and/or immunosuppressants) while being naïve to advanced therapy (biologics or targeted small molecules, e.g., Approved anti-tumor necrosis factor [TNF], Approved anti-interleukin [IL]-12/IL-23, Approved anti-integrin, Approved sphinsosine-1-phosphate [S1P] receptor modulators, Approved JAK inhibitors, etc.) OR inadequate response, loss of response, and/or intolerance to prior advanced therapy

Exclusion criteria 6

1. Severe UC as evidenced by any of the following: – Hospitalization for the treatment of UC ≤ 4 weeks prior to randomization or, in the physician's judgement, is likely to require hospitalization for medical care or surgical intervention of any kind for UC (e.g., colectomy) during the study - Current evidence of fulminant colitis, toxic megacolon, or recent history (within 6 months) of toxic megacolon, or bowel perforation. - Prior extensive colonic resection, subtotal, or total colectomy, or planned surgery for UC during the study
2. Current diagnosis of Crohn's disease (CD), abdominal / intrabdominal/ perianal fistula and / or abscess, indeterminant colitis, IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or active diverticular disease
3. Presence of an ostomy or ileoanal pouch
4. Current diagnosis or suspicion of primary sclerosing cholangitis
5. Any major surgery within 6 weeks prior to screening or a major surgery planned during the study.
6. Known exposure to anti-TL1A (afimkibart/RO7790121 [RVT-3101]/PF-06480605) or any type of anti-TL1A therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Clinical remission, defined as modified Mayo Score (mMS) ≤ 2 with stool frequency subscore (SFS) = 0 or 1, rectal bleeding subscore (RBS) = 0, and endoscopic subscore (ES) = 0 or 1, at Week 12

Secondary endpoints 20

1. 1. Partial modified Mayo Score (pmMS), defined as SFS + RBS, from baseline to Week 2
2. 2. Endoscopic improvement, defined as ES = 0 or 1, at Week 12
3. 3. Endoscopic remission, defined as ES = 0, at Week 12
4. 4. Clinical response, defined as a decrease in mMS of at least 2 points and 30% from baseline and either a decrease in RBS ≥ 1 or RBS = 0 or 1, at Week 12
5. 5. Histologic improvement, defined as Geboes ≤ 3.1 at Week 12
6. 6. Histologic remission, defined as Geboes < 2B at Week 12
7. 7. Histologic-endoscopic mucosal improvement, defined as Geboes ≤ 3.1 and ES = 0 or 1, at Week 12
8. 8. Histologic-endoscopic remission, defined as Geboes < 2B and ES = 0 or 1, at Week 12
9. 9. Among biomarker-defined subgroups of participants: Clinical remission at Week 12
10. 10. Among biomarker-defined subgroups of participants: Endoscopic improvement at Week 12
11. 11. Bowel urgency from baseline through Week 12
12. 12. Abdominal pain from baseline through Week 12
13. 13. Fatigue, as measured by Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F), from baseline to Week 12
14. 14. Inflammatory Bowel Disease Questionnaire (IBDQ) from baseline to Week 12
15. 15. Overall change in UC symptoms, as measured by Patient Global Impression of Change (PGIC), from baseline to Week 2 and Week 12
16. 16. Overall severity in UC symptoms, as measured by Patient Global Impression of Severity (PGIS), from baseline to Week 2 and Week 12
17. 17. Incidence and severity of the following: adverse events
18. 18. Incidence and severity of the following: serious adverse events
19. 19. Incidence and severity of the following: adverse events leading to study treatment discontinuation
20. 20. Incidence and severity of the following: adverse events of special interest

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 12

Locations

16 EU/EEA countries · 72 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 198 files

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

Application history

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