A study to investigate the efficacy and safety of brivekimig in adult participants with ulcerative colitis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

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 2025 → ongoing

Decision date (initial)

2025-08-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Développement

External identifiers

EU CT number

2024-515241-41-00

WHO UTN

U1111-1305-7281

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Assess the efficacy of different dose regimens of brivekimig in inducing clinical remission in participants with moderate to severe UC.

Secondary objectives 5

1. Assess the effect of different dose regimens of brivekimig in inducing endoscopic improvement, endoscopic response and endoscopic remission in participants with UC.
2. Assess the effect of different dose regimens of brivekimig on clinical remission and clinical response in participants with UC.
3. Assess the effect of different dose frequences of brivekimig on disease-specific QOL in participants with UC.
4. Assess brivekimig PK in participants with UC
5. Assess the safety and tolerability of brivekimig in participants with UC.

Conditions and MedDRA coding

Ulcerative Colitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Participant must be 18 to 75 years of age inclusive, at the time of signing the informed consent.
2. Participants have had clinical evidence of active UC for >3 months before Screening as confirmed by endoscopy during the screening period.
3. Participants must have active moderate to severe UC at Baseline as defined by mMS of 5 to 9 (without the PGA, with a minimum RB subscore of >1 and SF subscore of >1, mMES >2 )
4. Participants must have a minimum disease extent of 15 centimeters from the anal verge.
5. Must have received prior treatment for UC (either “a” or “b” below or combination of both): a) History of inadequate response to, loss of response to or intolerance to standard treatment with any of the following compounds: amino-salicylates, corticosteroids (oral or intravenous), MTX, AZA, or 6MP, or history of corticosteroid dependence (defined as an inability to successfully taper corticosteroids without recurrence of UC) AND history of no prior exposure to approved ATs, such as a biologic agent used to treat UC (eg, anti-TNFs, anti-integrins, anti-IL-12/IL-23, or anti-IL-23) or advanced small molecules used to treat UC (JAKis or S1PR modulators). b) History of inadequate response to, loss of response to or intolerance to treatment with >1 approved AT such as a biologic agent used to treat UC (eg, anti-TNFs, anti-integrins, anti-IL-12/IL-23, or anti-IL-23) or advanced small molecules used to treat UC (JAKis or S1PR modulators).
6. Oral corticosteroids must be at a stable dose >2 weeks (dose not exceeding 25 mg/day prednisone or prednisone-equivalent dose of ≤20 mg/day, or ≤9 mg/day of budesonide have been at a stable dose for at least 3 weeks prior to baseline or stopped at least 3 weeks prior baseline.
7. Participants on MTX, AZA, or 6-MP must be on; and on a stable dose for at least 4 weeks prior to baseline; if stopped, medication must have been discontinued at least 4 weeks prior to baseline./
8. Participants on oral 5-aminosalicylates, mesalamine, or sulfasalazine must be on a stable dose for >2 weeks prior baseline stopped treatment at least 2 weeks prior to baseline./
9. Participants on biologics must have 1) last administration at least 8 weeks prior to enrollment OR 2) undetectable level of the biologic in their blood prior to enrollment.
10. Participants who have been diagnosed with UC for ≥8 years must be up to date on their colorectal cancer screening per local guidelines by the time of randomization.
11. All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a) Male participants Male participants are eligible to participate if they agree to the following during the study Treatment Period and for at least 5 months after the last administration of study intervention: - Refrain from donating or cryopreserving sperm. PLUS, either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent. OR - Must agree to use contraception/barrier as detailed below. A male condom; the participant should also be advised of the benefit for a female partner to use a highly effective method of contraception as described in Appendix 4 Contraceptive and barrier guidance (Section 10.4) as a condom may break or leak when having sexual intercourse with a WOCBP who is not currently pregnant. b) Female participants - A female participant is eligible to participate if she is incapable of becoming pregnant, not pregnant, or breastfeeding, and one of the following conditions applies: - Is a WONCBP as defined in Appendix 4 Contraceptive and barrier guidance (Section 10.4). OR - Is a WOCBP and agrees to use a contraceptive method that is highly effective, with a failure rate of <1% per year, preferably with low user dependency, as defined in Appendix 4 Contraceptive and barrier guidance (Section 10.4) during the study treatment period (to be effective before starting the intervention) and for at least 5 months after the last administration of study intervention. - A WOCBP must have a negative highly sensitive pregnancy test (serum as required by local regulations) within 28 (+7 if needed) days before the first administration of study intervention, see Section 8.3.6. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
12. Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion criteria 42

1. Participants with Crohn’s Disease.
2. Known history of or suspected significant current immunosuppression, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
3. History of solid organ transplant.
4. History of splenectomy.
5. History of moderate to severe congestive heart failure (New York Health Association Class III or IV), or recent cerebrovascular accident, or any other condition which, in the opinion of the Investigator, would put the participant at risk by participation in the protocol.
6. History of demyelinating disease (including myelitis), family history of demyelinating disease, or neurologic symptoms suggestive of demyelinating disease.
7. Participants with a history of malignancy or lymphoproliferative disease other than adequately treated localized carcinoma in situ of the cervix or nonmetastatic squamous cell carcinoma, or nonmetastatic basal cell carcinoma of the skin.
8. Participants with a diagnosis of inflammatory conditions other than UC (including but not limited to systemic lupus erythematosus, systemic sclerosis, myositis, rheumatoid arthritis, primary biliary cirrhosis, multiple sclerosis, Behcet’s disease, sarcoidosis, etc.).
9. Participants with diagnosis of indeterminate colitis or microscopic colitis.
10. Participants with fecal sample positive for culture/ova for aerobic pathogens at Screening including: Aeromonas, Plesiomonas, Shigella, Salmonella, Yersinia, Campylobacter, and E. coli spp. or positive for Clostridium difficile B toxin in stools, or positive on any active infection in the stool with these parasites.
11. Participants with prior colectomy or anticipated colectomy during their participation in the study.
12. Participants with presence of ileal pouch or ostomy.
13. Participants with fulminant disease or toxic megacolon.
14. Participants with colonic dysplasia except for adenoma.
15. Participants with intestinal failure or short bowel syndrome requiring Total Parenteral Nutrition.
16. History of recurrent or recent serious infection (eg, pneumonia, septicemia) within 4 weeks of screening, or infection(s) requiring hospitalization or treatment with IV anti-infectives (antibiotics, antivirals, antifungals, antihelminthics) within 30 days prior to baseline, or infections(s) requiring oral anti-infectives (antibiotics, antivirals, antifungals, antihelminthics) within 14 days prior to baseline, except as required as part of an anti-TB regimen.
17. History of HIV infection or positive HIV serology at Screening.
18. History of Interstitial Lung Disease.
19. Participants with any of the following result at Screening: - Positive HBs Ag or, • Positive total anti-HBc AB, • Positive HCV antibody confirmed by positive HCV RNA (participants with HCVAb and negative HCV RNA may be included).
20. Elective surgery within 4 weeks prior to the Screening Visit or with planned surgery during the treatment period, or in the period up to 3 months following the last dose of IMP.
21. Positive COVID-19 molecular test, suspected of having COVID-19 infection, or known exposure to COVID-19 during the screening period.
22. Participants who are simultaneously on AZA, 6-MP, and corticosteroids <4 weeks prior to baseline (participants may be on any two of these therapies >4 weeks prior to baseline).
23. Participants on cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, or tacrolimus treatment within 28 days prior to baseline..
24. Participants who have received any of the following agents according to the following timelines: • Anti-TNF therapy (eg, infliximab, adalimumab, certolizumab pegol): within 8 weeks of baseline.* • Anti-integrin therapy (eg, vedolizumab): within 8 weeks of baseline.* • Anti-IL12/23 therapy (eg, ustekinumab): within 8 weeks of baseline.* • Anti-IL-23 therapy (eg, risankizumab, mirikizumab): within 8 weeks of baseline.* • JAKi (eg, tofacitinib, filgotinib, upadacitinib) within 2 weeks of randomization; • S1Prm 2 weeks or less3 half-lives (whichever is longer) within 2 weeks of randomization. *Note: If there is proper documentation of an undetectable drug level measured by a commercially available assay for any of the approved biologics above, there is no mínimum washout prior to randomization
25. Participants with previous exposure to natalizumab (Tysabri®).
26. Participants on anti-diarrheals within 2 weeks prior to screening and during the screening period.
27. Participants on prednisone >20 mg/day (or equivalent) at baseline.
28. Participants on budesonide >9 mg/day at baseline.
29. Participants who received IV corticosteroids or cytapheresis therapy within 2 weeks prior to screening or during baseline.
30. Participants who were rectally administered topical 5-aminosalicylate or corticosteroids within 2 weeks prior to screening colonoscopy..
31. Participants who received therapeutic enema or suppository, within 2 weeks prior to or during screening.
32. Participants who received antibiotics for UC or gastrointestinal infection within 4 weeks prior to baseline.
33. Treatment with a live (attenuated) immunization within 12 weeks prior to baseline; treatment with a non-live immunization 2 weeks prior to baseline; completion of COVID-19 vaccine within 14 days prior to baseline.
34. Participants who have taken other investigational medications within 2 months or 5 half-lives (whichever is longer) prior to screening.
35. Exclusion related to TB infection: - Active TB infection a history of incompletely treated TB infection regardless of screening QuantiFERON TB gold test result. - Participants with QuantiFERON TB gold test positive or 2 indeterminate test results (no active disease) are excluded from the study unless the following conditions are met: - Participants with a history of prior documented completed chemoprophylaxis for latent TBI (eg, acceptable treatments would be 9 months of isoniazid 300 mg PO daily or equivalent proven regimen per local guidelines) or treatment of active TBI who has obtained consultation with a specialist to rule out active TBI or treat active TBI.- Participants with no prior history of chemoprophylaxis for latent TBI or treatment for active TBI but have obtained consultation with a specialist to initiate an appropriate regimen of chemoprophylaxis, based on local epidemiology and applicable guidelines and have demonstrated compliance and tolerated treatment for ≥1 month. -Known clinically significant abnormality consistent with prior/active TB infection based upon previously performed chest radiograph with at least posterior-anterior view (radiograph must be taken within 12 weeks prior to Screening Visit or during the screening period). Additional lateral view is recommended but not required. - Suspected extrapulmonary TB infection regardless of screening QuantiFERON TB Gold test result. - Participants at high risk of contracting TB, such as close contact with individuals with active or latent TB. - Participant who received Bacille Calmette-Guérin vaccination within 12 months prior to screening.
36. Any of the following laboratory abnormalities at the Screening Visit: - Hemoglobin <8 g/dL. - ANC <1500/mm3. - Platelet count <100 000/mm3. - Creatinine clearance <60 mL/min using Cockcroft-Gault equation. - ALT, AST, or ALP >2 × ULN. - Total bilirubin >2 × ULN or, ≥3 × ULN if diagnosed with Gilbert's syndrome verified by genetic testing. - Fasting triglyceride level ≥300 mg/dL.
37. Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
38. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
39. Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with Section 1.61 of the ICH-GCP Ordinance E6).
40. Sensitivity to any of the study interventions, or components thereof, or drug, or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.
41. Participants presenting with conditions/situations such as: - Short life expectancy. - Requirement for concomitant treatment that could bias primary evaluation. - Uncooperative behavior or any condition that could make the participant potentially non-compliant to the study procedures.
42. Any country-related specific regulation that would prevent the participant from entering the study – see Section 10.7.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants who achieve clinical remission at the end of Week 16 by mMS. Clinical remission is defined as an mMS score of 0 to 2, including SF subscore of 0 or 1, RB subscore of 0, and mMES of 0 or 1 confirmed by central reader (score of 1 does not include friability)./

Secondary endpoints 14

1. Proportion of participants who achieve endoscopic improvement at Week 16. Endoscopic improvement is defined as an mMES of 0 or 1 (where 1 does not include friability).
2. Proportion of participants who achieve endoscopic response at Week 16. Endoscopic response is defined as an mMES decrease of at least 1.
3. Proportion of participants who achieve endoscopic remission at Week 16. Endoscopic remission is defined as mMES of 0 confirmed by central reader.
4. Proportion of participants who achieve endoscopic improvement at Week 52. Endoscopic improvement is defined as an mMES of 0 or 1 (where 1 does not include friability).
5. Proportion of participants who achieve clinical remission at Week 16 by total MS defined as MS ≤2 with no subscore >1.
6. Proportion of participants who achieve clinical response at Week 16 by total MS. Clinical response by total MS is defined as a decrease from baseline in the MS of ≥3 points and at least 30% reduction from baseline, and a decrease in the RB subscore of ≥1 or an absolute RB subscore of 0 or 1.
7. Proportion of participants who achieve clinical response at Week 16 by mMS. Clinical response by mMS is defined as a decrease from baseline in the mMS of ≥2 points and an improvement of ≥30% from baseline plus a decrease in RB subscore ≥1 or an absolute RB subscore ≤1.
8. Proportion of participants who achieve clinical remission at Week 52 by mMS. Clinical remission is defined as an mMS score of 0 to 2, including SF subscore of 0 or 1, RB subscore of 0, and mMES of 0 or 1 confirmed by central reader (score of 1 does not include friability).
9. Change from baseline in IBDQ at Week 16 to capture the patient’s experience of IBD on 4 domains of functioning and well-being: bowel and systemic symptoms and emotional and social function.
10. Serum brivekimig concentrations throughout the study.
11. Incidence of ADAs over time.
12. Number (percentage) of participants with any TEAEs during the Induction and Maintenance treatment periods.
13. Number (percentage) of participants with any TEAEs during the LTE period.
14. Change from baseline in IBDQ at Week 52.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 6

Locations

6 EU/EEA countries · 29 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 88 files

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

Application history

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