SAR442970 for Ulcerative colitis

Inclusion criteria

• {"criterion_text":"- Participant must be 18 to 75 years of age inclusive, at the time of signing the informed consent.\n- 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.\n- 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.\n- 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.\n- Participants have had clinical evidence of active UC for >3 months before Screening as confirmed by endoscopy during the screening period.\n- 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 )\n- Participants must have a minimum disease extent of 15 centimeters from the anal verge.\n- 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).\n- 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.\n- 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./\n- 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./\n- 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."}

Exclusion criteria

• {"criterion_text":"- Participants with Crohn’s Disease.\n- 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.\n- Participants with prior colectomy or anticipated colectomy during their participation in the study.\n- Participants with presence of ileal pouch or ostomy.\n- Participants with fulminant disease or toxic megacolon.\n- Participants with colonic dysplasia except for adenoma.\n- Participants with intestinal failure or short bowel syndrome requiring Total Parenteral Nutrition.\n- 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.\n- History of HIV infection or positive HIV serology at Screening.\n- History of Interstitial Lung Disease.\n- 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).\n- 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.\n- 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.\n- Positive COVID-19 molecular test, suspected of having COVID-19 infection, or known exposure to COVID-19 during the screening period.\n- 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).\n- Participants on cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, or tacrolimus treatment within 28 days prior to baseline..\n- 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\n- Participants with previous exposure to natalizumab (Tysabri®).\n- Participants on anti-diarrheals within 2 weeks prior to screening and during the screening period.\n- Participants on prednisone >20 mg/day (or equivalent) at baseline.\n- Participants on budesonide >9 mg/day at baseline.\n- Participants who received IV corticosteroids or cytapheresis therapy within 2 weeks prior to screening or during baseline.\n- History of solid organ transplant.\n- Participants who were rectally administered topical 5-aminosalicylate or corticosteroids within 2 weeks prior to screening colonoscopy..\n- Participants who received therapeutic enema or suppository, within 2 weeks prior to or during screening.\n- Participants who received antibiotics for UC or gastrointestinal infection within 4 weeks prior to baseline.\n- 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.\n- Participants who have taken other investigational medications within 2 months or 5 half-lives (whichever is longer) prior to screening.\n- 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.\n- 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.\n- Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.\n- 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.\n- 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).\n- History of splenectomy.\n- 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.\n- 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.\n- Any country-related specific regulation that would prevent the participant from entering the study – see Section 10.7.\n- 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.\n- History of demyelinating disease (including myelitis), family history of demyelinating disease, or neurologic symptoms suggestive of demyelinating disease.\n- 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.\n- 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.).\n- Participants with diagnosis of indeterminate colitis or microscopic colitis."}

Primary endpoints

• {"endpoint_text":"- 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)./","definition_or_measurement_approach":"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). Measured at end of Week 16 using mMS and central reader confirmation."}

Secondary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Endoscopic improvement defined as an mMES of 0 or 1 (where 1 does not include friability), assessed at Week 16."}
• {"endpoint_text":"- Proportion of participants who achieve endoscopic response at Week 16. Endoscopic response is defined as an mMES decrease of at least 1.","definition_or_measurement_approach":"Endoscopic response defined as decrease in mMES of ≥1 from baseline, assessed at Week 16."}
• {"endpoint_text":"- Proportion of participants who achieve endoscopic remission at Week 16. Endoscopic remission is defined as mMES of 0 confirmed by central reader.","definition_or_measurement_approach":"Endoscopic remission defined as mMES = 0 confirmed by central reader, assessed at Week 16."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Endoscopic improvement defined as mMES 0 or 1 (1 excludes friability), assessed at Week 52."}
• {"endpoint_text":"- Proportion of participants who achieve clinical remission at Week 16 by total MS defined as MS ≤2 with no subscore >1.","definition_or_measurement_approach":"Clinical remission by total MS defined as MS ≤2 and no subscore >1, assessed at Week 16."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Clinical response by total MS: decrease ≥3 points and ≥30% from baseline plus RB subscore decrease ≥1 or absolute RB 0 or 1; assessed Week 16."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Clinical response by mMS: decrease ≥2 points and ≥30% from baseline plus RB subscore decrease ≥1 or absolute RB ≤1; assessed Week 16."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Clinical remission by mMS at Week 52 using same mMS definition as Week 16, central reader confirmation."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Change from baseline in IBDQ score at Week 16 across four domains (bowel, systemic, emotional, social)."}
• {"endpoint_text":"- Serum brivekimig concentrations throughout the study.","definition_or_measurement_approach":"Pharmacokinetic measures: serum concentrations of brivekimig measured at scheduled timepoints throughout study."}
• {"endpoint_text":"- Incidence of ADAs over time.","definition_or_measurement_approach":"Measurement of anti-drug antibodies (ADA) incidence over time using central immunogenicity assays."}
• {"endpoint_text":"- Number (percentage) of participants with any TEAEs during the Induction and Maintenance treatment periods.","definition_or_measurement_approach":"Safety endpoint: count and percent of participants with any treatment-emergent adverse events during induction and maintenance periods."}
• {"endpoint_text":"- Number (percentage) of participants with any TEAEs during the LTE period.","definition_or_measurement_approach":"Safety endpoint during long-term extension: number and percent with TEAEs."}
• {"endpoint_text":"- Change from baseline in IBDQ at Week 52.","definition_or_measurement_approach":"Change from baseline in IBDQ at Week 52."}

Methods

• Country-specific recruitment materials (flyers, patient posters, patient brochures) available (documents: K2_* for HU, ES, CZ, DE, FR, PL).
• Online outreach text / online recruitment via patient recruitment websites (documents: Online Outreach Text, Patient Recruitment Website per country).
• Use of third-party recruitment platform/process (Longboat/Advarra privacy policy documents present for multiple countries).
• Study visit guides and thank-you cards provided to participants (country-specific study materials).
• Recruitment and informed consent procedure forms (K1 documents) specifying local recruitment process (e.g., K1_ACT18134_HU, K1_ACT18134_DE, K1_ACT18134_ES, K1_ACT18134_CZ, K1_ACT18134_PL, K1_ACT18134_FR).

Hungary

Earliest CTIS Part Ii Submission Date

18-07-2025

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

280

Number Of Sites

3

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

17-07-2025

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

279

Number Of Sites

3

Number Of Participants

4

Czechia

Earliest CTIS Part Ii Submission Date

24-07-2025

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

277

Number Of Sites

2

Number Of Participants

8

Germany

Earliest CTIS Part Ii Submission Date

02-06-2025

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

326

Number Of Sites

5

Number Of Participants

15

France

Earliest CTIS Part Ii Submission Date

21-07-2025

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

275

Number Of Sites

7

Number Of Participants

6

Poland

Earliest CTIS Part Ii Submission Date

25-07-2025

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

273

Number Of Sites

9

Number Of Participants

20

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Fortrea Inc.

Responsibilities

codes: [1,10,12,2,5]

Name

Alimentiv

Responsibilities

codes: [7]

Name

Fisher Clinical Services Inc.

Responsibilities

codes: [14]

Name

Endpoint Clinical Inc.

Responsibilities

codes: [3]

Name

Medidata Solutions Inc.

Responsibilities

codes: [7]

Name

Labcorp Central Laboratory Services LP

Responsibilities

codes: [4]

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"codes: [1,10,12,2,5]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Alimentiv","duties_or_roles":"codes: [7]","organisation_type":"Industry"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"codes: [14]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"codes: [3]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"codes: [7]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"codes: [4]","organisation_type":"Pharmaceutical company"}