Efficacy and Safety of SAR339658 in Patients With Moderate to Severe Ulcerative Colitis (FUSCIA)

Inclusion criteria: o Male or Female ≥18 and ≤70 years old o History of active ulcerative colitis of at least 3 months duration o Active UC should be confirmed by colonoscopy or flexible sigmoidoscopy during the screening period within 7 days prior to randomization. o Moderate to severe ulcerative colitis at time of screening, confirmed by Mayo score ≥6 to 12 and endoscopy subscore of ≥2 despite treatment with immunosuppressants and/or anti-TNFs: o Immunosuppressants: Patient must be on concurrent treatment with or have had an inadequate response to (did not respond to or lost response to) or be intolerant to immunosuppressants such as azathioprine, 6-mercaptopurine, or methotrexate. AND/OR o TNF-alpha antagonists: Patient must have had an inadequate response or lost response or be intolerant to TNF-alpha antagonists o Fecal calprotectin ≥200mg/kg o Patients on corticosteroids must be on a stable dose ≥2 weeks prior to screening o Patients on azathioprine, 6- mercaptopurine or methotrexate must be on treatment for at least 12 weeks prior to screening; and on a stable dose ≥4 weeks prior to screening o Patients on oral 5-aminosalicylates, mesalamine or sulfasalazine must be on a stable dose for ≥4 weeks prior to screening o Patients naïve to anti-TNF alpha or non responder (primary or secondary) or intolerant to anti-TNF alpha o Signed written informed consent Exclusion criteria: o Patients with Crohn's Disease (CD) o Diagnosis of indeterminate colitis o Patients with stool sample positive for ova, parasites, or positive culture for aerobic pathogens including: Aeromonas, Plesiomonas, Shigella, Yersinia, Campylobacter and E. Coli spp. or positive for Clostridium difficile B toxin in stools. o Patients with prior colectomy or anticipated colectomy during their participation in the study o Presence of ileal pouch or ostomy o Fulminant disease or toxic megacolon o Colonic dysplasia except for adenoma o Total Parenteral Nutrition (TPN) o Cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide or tacrolimus within 2 months prior to screening o Previous exposure to natalizumab (Tysabri®) or vedolizumab o Antidiarrheals within 2 weeks prior to screening o Prednisone >40 mg/day (or equivalent) o Budesonide >9 mg/day o Received intravenous corticosteroids within 2 weeks prior to screening or during screening o Rectally administered topical 5-aminosalicylate or corticosteroids within 4 weeks prior to screening o Received therapeutic enema or suppository, other than required for colonoscopy or flexible sigmoidoscopy within 4 weeks prior to screening or during screening o Antibiotics for UC or gastrointestinal infection within 4 weeks prior to screening o Patient who has previously participated in any clinical trial of GBR500 / SAR339658 o Patient who has taken other investigational medications within 2 months or 5 half lives, (whichever is longer) prior to screening o Use of any biologics for the treatment of UC in the previous 8 weeks before screening o Requirement for concomitant treatment that could bias primary evaluation o Pregnant or breast-feeding women o Women of childbearing potential not protected by highly effective contraceptive method of birth control o Patient with latent or active tuberculosis (TB) o Any signs or symptoms suggestive of active TB upon medical history or clinical examination o Patients with a positive QuantiFERON TB Gold Test o Chest radiograph within 3 months prior to the inclusion visit consistent with prior tuberculosis infection including, but not limited to, apical scarring, apical fibrosis, or multiple calcified granulomasa. This does not include non-caseating granulomasa o Patients with close contact with a person with active tuberculosis o Patient with a history of listeriosis or tuberculosis (unless it is documented that they were adequately treated) o Administration of any live (attenuated) vaccine within 3 months prior to the screening Visit (eg, varicella-zoster vaccine, oral polio, rabies) o Positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis B core antibody (HBcAb); and/or positive Hepatitis C antibody (HCV) at the Screening Visit o Prior opportunistic infections within six months prior to screening or while receiving anti-TNF treatment o History of a hypersensitivity reaction, other than localized injection site reaction (ISR), to any biological molecule o History or any current signs of demyelinating disease or any neurological disease that can by the opinion of Investigator interfere with study safety assessments including assessment for PML o Patients with bleeding disorders or known platelet dysfunction The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.