SAR442970 for Crohn's disease

Inclusion criteria

• {"criterion_text":"- Male or female participants aged 18 to 75 years, inclusive, at the time of signing the ICF."}
• {"criterion_text":"- Participants with confirmed diagnosis of CD for at least 3 months prior to screening. Appropriate documentation of biopsy (histology), endoscopy and/or radiology results consistent with the diagnosis of CD, as determined by the Investigator, must be available."}
• {"criterion_text":"- Participants with moderate to severely active CD, defined as: a) Persistently active disease with a CDAI score of 220 to 450, with endoscopic SES-CD score (excluding the presence of narrowing component) ≥6 (or ≥4 for participants with isolated ileal disease), as confirmed by a central reader, AND b) Average daily very soft or liquid SF ≥4.0 and/or average daily abdominal pain score ≥2.0 at screening."}
• {"criterion_text":"- Must have received prior treatment for CD (either \"a\" or \"b\" below or combination of both): 1. Having inadequate response to, loss of response to or intolerance to standard treatment with any of the following compounds: 5-ASAs, 6-MP, AZA, MTX, oral or IV corticosteroids or history of corticosteroid dependence (defined an inability to successfully taper corticosteroids without recurrence of CD) with NO prior AT exposure, OR 2. history of inadequate response to, loss of response to or intolerance to treatment with approved AT classes such as a biologic agent for CD (eg, anti-TNFs, antiintegrin except to natalizumab [Tysabri®] or oral carotegrast methyl [Carogra®], anti-IL- 12/23, anti- or a small molecule (such as JAKi or S1PRm). Please see Section 5.2 - E20 for details on washout periods."}
• {"criterion_text":"- Participant may be receiving a therapeutic dosage of the following drugs: • Oral 5-ASA compounds: prescribed dose must be stable for at least 2 weeks before baseline or stopped treatment at least 2 weeks prior to baseline. • Oral corticosteroids must be at a prednisone-equivalent dose of ≤20 mg/day, or ≤9 mg/day of budesonide and have been at a stable dose for at least 3 weeks prior to the baseline or stopped at least 3 weeks prior to baseline. • AZA, 6-MP, or MTX: if the prescribed dose has been stable for at least 4 weeks before baseline, or, if stopped, medication must have been discontinued at least 4 weeks prior to baseline to be considered eligible for enrollment. • Antibiotics prescribed at doses that have been stable for at least 4 weeks before baseline, or if stopped, medication must have been discontinued at least 4 weeks prior to baseline to be considered eligible for enrollment."}
• {"criterion_text":"- 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 agrees to refrain from donating or cryopreserving eggs (oocytes, ova) during the study treatment period and for at least 5 months after the last administration of study intervention - AND 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 Pregnancy testing). 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."}
• {"criterion_text":"- Willing to participate, able to provide written ICF and be compliant with the schedule of protocol assessments. In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participant’s legally authorized representative."}

Exclusion criteria

• {"criterion_text":"- Participants with active UC, indeterminate colitis, adenomatous colonic polyps not excised, colonic mucosal dysplasia (low- or high-grade dysplasia) or short bowel syndrome."}
• {"criterion_text":"- Participants who have previously received stem cell transplantation (except for local stem cell therapy for complex perianal fistula)."}
• {"criterion_text":"- Participants who have been the recipient of an organ transplant which requires continued immunosuppression."}
• {"criterion_text":"- History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease."}
• {"criterion_text":"- Treatment with a live (attenuated) immunization within 12 weeks prior to baseline; treatment with a non-live immunization within 2 weeks of baseline; completion of COVID-19 vaccine within 14 days prior to baseline."}
• {"criterion_text":"- Previous treatment or exposure with OX40 or OX40L inhibitor"}
• {"criterion_text":"- Participants who have taken other investigational medications within 30 days or 5 half-lives (whichever is longer) prior to screening."}
• {"criterion_text":"- Participants with following ongoing known complications of CD: • Active perianal disease, likely to require acute medical or surgical treatment. Note: known stable perianal fistulae without associated undrained abscess and with no anticipated need for surgery may be permitted. Recommend imaging for participants with active perianal disease within approximately 6 months of the Baseline Visit to assess for complications. • Enterocutaneous, intraabdominal, and anogenital fistulae. • Current or suspected abscess. Note: recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks before baseline, or 8 weeks before baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery. • Symptomatic bowel strictures. • Two entire missing segments (either surgically removed or not visible during most recent colonoscopy) of the following five segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum. • Fulminant colitis. • Toxic megacolon.• Or any other manifestation that might require bowel surgery while enrolled in the study. • Participant with ostomy or ileoanal pouch. • Participant diagnosed with conditions that could interfere with drug absorption including but not limited to short bowel syndrome. • Participant with surgical bowel resection within the past three months prior to screening, or a history of >3 bowel resections."}
• {"criterion_text":"- Exclusion related to TB or NTM infection: - Active TB or NTM infection: a history of incompletely treated TB or NTM 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 per os (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 prior to screening. - Clinically significant abnormality consistent with active TB or NTM infection based upon 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 or NTM 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 Guerin (BCG) vaccination within 12 months prior to screening."}
• {"criterion_text":"- At screening visit, participants with presence of any of the following laboratory abnormalities: - Hemoglobin <8.0 g/dL. - Absolute neutrophil count <1500/mm3. - Platelet count <100 000 platelets/mm3. - Creatinine clearance <60 mL/min using Cockcroft Gault equation. - ALT or AST or ALP >2 × ULN. - Total bilirubin >2 × ULN; unless the participant has been diagnosed with Gilbert disease documented by genetic testing, in which case Total bilirubin >3 × ULN. - Fasting triglyceride level ≥ 300 mg/dL. - Retest can be done to reassess the eligibility during screening period as per Investigator's judgment that observed abnormality is not clinically significant and not consistent with participant's medical history."}
• {"criterion_text":"- Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized."}
• {"criterion_text":"- Participants who received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to baseline"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participant with fecal sample positive for culture for aerobic pathogens at screening including Aeromonas, Plesiomonas, Shigella, Salmonella, Yersinia, Campylobacter, or E. coli spp. or positive for Clostridium difficile B and A toxin in stools during screening."}
• {"criterion_text":"- 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, anthelminthics) within 30 days prior to baseline, or infections(s) requiring oral anti-infectives (antibiotics, antivirals, antifungals, anthelminthics) within 14 days prior to baseline, except as required as part of an anti-TB regimen."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- History of splenectomy."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participants who received fecal microbial transplantation within 30 days prior to baseline."}
• {"criterion_text":"- History of interstitial lung disease."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Positive COVID-19 molecular or rapid test, suspected of having COVID-19 infection, or known exposure to COVID-19 during the screening period."}
• {"criterion_text":"- The participant who receive any live (or attenuated) vaccine during the whole study and for 6 months after last IMP administration."}
• {"criterion_text":"- Participants requiring or receiving any parental nutrition and/or exclusive enteral nutrition."}
• {"criterion_text":"- Participants with any of the following result at Screening: • Positive HBsAg or, • Positive total anti-HBcAB, • Positive HCV antibody confirmed by positive HCV RNA (participants with HCVAb and negative HCV RNA may be included). • HIV-1 or HIV-2 positive antibody test. Any other active, chronic, or recurrent infection, including recurrent or disseminated herpes zoster or disseminated herpes simplex."}
• {"criterion_text":"- Participants with CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic or ileal involvement."}
• {"criterion_text":"- Participants who have ever been exposed to natalizumab (Tysabri®) or oral carotegrast methyl (Carogra®), or received any of the following agents: • Anti-TNF therapy (eg, infliximab, adalimumab, certolizumab): 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 and/or S1Prm: within 2 weeks of baseline. • Experimental biologic CD therapy: within 8 weeks of baseline or 5 times the terminal halflife of the IMP, whichever is longer. *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 minimum washout prior to randomization."}
• {"criterion_text":"- Participants who received IV corticosteroids within 14 days prior to baseline."}
• {"criterion_text":"- Participants who received therapeutic enema(s) or suppository(ies) (eg, rectal 5-ASA/corticosteroids) within 14 days of screening colonoscopy used during the study."}
• {"criterion_text":"- Participants who received apheresis (eg, adacolumn apheresis) within 60 days prior to screening or during screening period."}
• {"criterion_text":"- Any history of clinically significant (as per Investigator's judgement) drug or alcohol abuse in last six months."}

Primary endpoints

• {"endpoint_text":"- Percentage of participants who achieve endoscopic response at Week 16. Endoscopic response is defined as decrease in SES-CD >50% from baseline (or a decrease of at least 2 points for subjects with a baseline score of 4 or more and isolated ileal disease) based on central reading.","definition_or_measurement_approach":"Endoscopic response is defined as decrease in SES-CD >50% from baseline (or a decrease of at least 2 points for subjects with a baseline score of 4 or more and isolated ileal disease) based on central reading."}

Secondary endpoints

• {"endpoint_text":"- Percentage of participants who achieve clinical remission based on CDAI at Week 16. CDAI clinical remission is defined as CDAI score <150.","definition_or_measurement_approach":"CDAI clinical remission is defined as CDAI score <150 at Week 16."}
• {"endpoint_text":"- Percentage of participants who achieve PRO-2 clinical remission at Week 16. PRO-2 clinical remission is defined as using the average daily SF ≤3 and not worse than baseline and average daily AP ≤1 and not worse than baseline.","definition_or_measurement_approach":"PRO-2 clinical remission defined as average daily stool frequency (SF) ≤3 and not worse than baseline and average daily abdominal pain (AP) ≤1 and not worse than baseline at Week 16."}
• {"endpoint_text":"- Percentage of participants who achieve endoscopic remission at Week 16. Endoscopic remission is defined as SES-CD ≤4 and at least 2 point reduction versus baseline and no subscore >1 in any individual variable based on central reading.","definition_or_measurement_approach":"Endoscopic remission defined as SES-CD ≤4 and at least 2-point reduction versus baseline and no subscore >1 in any individual variable based on central reading at Week 16."}
• {"endpoint_text":"- Percentage of participants who achieve at Week 16 both clinical remission based on CDAI score and endoscopic response based on SES-CD.","definition_or_measurement_approach":"Composite of CDAI clinical remission (CDAI <150) and endoscopic response (SES-CD criteria) at Week 16."}
• {"endpoint_text":"- Percentage of participants who achieve CDAI clinical response at Week 16. CDAI clinical response is defined as reduction of CDAI ≥100 points from baseline.","definition_or_measurement_approach":"CDAI clinical response defined as reduction of CDAI ≥100 points from baseline at Week 16."}
• {"endpoint_text":"- Change from baseline in the IBDQ score at Week 16.","definition_or_measurement_approach":"Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) score at Week 16."}
• {"endpoint_text":"- Change from baseline in FACIT-F score at Week 16.","definition_or_measurement_approach":"Change from baseline in FACIT-F (fatigue) score at Week 16."}
• {"endpoint_text":"- On-treatment serum concentrations of brivekimig at predefined timepoints.","definition_or_measurement_approach":"Pharmacokinetic measurement: on-treatment serum concentrations of brivekimig at predefined timepoints."}
• {"endpoint_text":"- Number and percentage of participants with any TEAEs during induction and maintenance and LTE treatment period.","definition_or_measurement_approach":"Safety endpoint: count and percent of participants with treatment-emergent adverse events (TEAEs) during induction, maintenance and long-term extension (LTE) periods."}
• {"endpoint_text":"- Number and percentage of participants with any TEAEs during open-label treatment period.","definition_or_measurement_approach":"Safety endpoint: count and percent of participants with TEAEs during open-label treatment period."}
• {"endpoint_text":"- Incidence of ADAs over time.","definition_or_measurement_approach":"Immunogenicity endpoint: incidence of anti-drug antibodies (ADAs) measured over time."}
• {"endpoint_text":"- Percentage of participants who achieve endoscopic remission based on centrally read SES-CD at Week 52.","definition_or_measurement_approach":"Endoscopic remission based on centrally read SES-CD at Week 52 (SES-CD criteria)."}
• {"endpoint_text":"- Percentage of participants who achieve endoscopic response at Week 52.","definition_or_measurement_approach":"Endoscopic response at Week 52 (SES-CD based criteria)."}

Methods

• Printed patient-facing materials (patient brochures, flyers, posters) available in multiple languages (e.g. English, Dutch, French, Spanish, Polish, Czech) for use at clinical sites (documents labelled K2_Recruitment materials_Flyer / Patient Brochure / Patient Poster / Patient Website). Associated recruitment packs are present for multiple participating countries (see recruitment documents associated with Belgium, France, Spain, Poland, Czechia, Germany).
• Online outreach and digital recruitment: online outreach text, patient recruitment websites and online adverts (documents K2_Recruitment materials_Online text, K2_Recruitment materials_Patient Website, K2_Recruitment Material_Online Outreach).
• Site-based recruitment via participating hospitals and gastroenterology clinics (on-site posters/flyers/clinic staff recruitment) — recruitment materials include study visit guides and patient brochures intended for clinic distribution.
• Use of third-party/online platform privacy policies for digital recruitment (Advarra Longboat privacy policy documents provided in multiple languages) indicating use of an online recruitment/consent/privacy workflow.

Belgium

Earliest CTIS Part Ii Submission Date

16-07-2025

Latest Decision Or Authorization Date

05-08-2025

Processing Time Days

20

Number Of Sites

1

Number Of Participants

1

France

Earliest CTIS Part Ii Submission Date

03-06-2025

Latest Decision Or Authorization Date

04-08-2025

Processing Time Days

62

Number Of Sites

4

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

18-07-2025

Latest Decision Or Authorization Date

08-08-2025

Processing Time Days

21

Number Of Sites

4

Number Of Participants

4

Poland

Earliest CTIS Part Ii Submission Date

18-07-2025

Latest Decision Or Authorization Date

11-08-2025

Processing Time Days

24

Number Of Sites

10

Number Of Participants

11

Czechia

Earliest CTIS Part Ii Submission Date

10-07-2025

Latest Decision Or Authorization Date

05-08-2025

Processing Time Days

26

Number Of Sites

5

Number Of Participants

6

Germany

Earliest CTIS Part Ii Submission Date

10-07-2025

Latest Decision Or Authorization Date

11-08-2025

Processing Time Days

32

Number Of Sites

5

Number Of Participants

5

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: 1,10,12,2,3,5,6,7,8

Name

Endpoint Clinical Inc.

Responsibilities

Code: 3

Name

Scarritt Group Inc.

Responsibilities

Code: 15 (Investigator`s meetings)

Name

Medidata Solutions Inc.

Responsibilities

Code: 7

Name

Fisher Clinical Services Inc.

Responsibilities

Code: 14

Name

Labcorp Central Laboratory Services LP

Responsibilities

Code: 4

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Codes: 1,10,12,2,3,5,6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scarritt Group Inc.","duties_or_roles":"Code: 15 (Investigator`s meetings)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"Code: 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"Code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Code: 4","organisation_type":"Pharmaceutical company"}