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

Inclusion criteria:

• Male or Female ≥18 and ≤70 years old

• History of active ulcerative colitis of at least 3 months duration

• Active UC should be confirmed by colonoscopy or flexible sigmoidoscopy during thescreening period within 7 days prior to randomization.

• Moderate to severe ulcerative colitis at time of screening, confirmed by Mayo score ≥6to 12 and endoscopy subscore of ≥2 despite treatment with immunosuppressants and/oranti-tumor necrosis factors (TNFs):

• Immunosuppressants: Patient must be on concurrent treatment with or have had aninadequate response to (did not respond to or lost response to) or be intolerantto immunosuppressants such as azathioprine, 6-mercaptopurine, or methotrexate.

• AND/OR

• TNF-alpha antagonists: Patient must have had an inadequate response or lostresponse or be intolerant to TNF-alpha antagonists

• Fecal calprotectin ≥200mg/kg

• Patients on corticosteroids must be on a stable dose ≥2 weeks prior to screening

• Patients on azathioprine, 6- mercaptopurine or methotrexate must be on treatment forat least 12 weeks prior to screening; and on a stable dose ≥4 weeks prior to screening

• Patients on oral 5-aminosalicylates, mesalamine or sulfasalazine must be on a stabledose for ≥4 weeks prior to screening

• Patients naïve to anti-TNF alpha or non-responder (primary or secondary) or intolerantto anti-TNF alpha

• Signed written informed consent

Exclusion criteria:

• Patients with Crohn's Disease

• Diagnosis of indeterminate colitis

• Patients with stool sample positive for ova, parasites, or positive culture foraerobic pathogens including: Aeromonas, Plesiomonas, Shigella, Yersinia, Campylobacterand E. Coli spp. or positive for Clostridium difficile B toxin in stools.

• Patients with prior colectomy or anticipated colectomy during their participation inthe study

• Presence of ileal pouch or ostomy

• Fulminant disease or toxic megacolon

• Colonic dysplasia except for adenoma

• Total Parenteral Nutrition

• Cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide or tacrolimuswithin 2 months prior to screening

• Previous exposure to natalizumab (Tysabri®) or vedolizumab

• Antidiarrheals within 2 weeks prior to screening

• Prednisone >40 mg/day (or equivalent)

• Budesonide >9 mg/day

• Received intravenous corticosteroids within 2 weeks prior to screening or duringscreening

• Rectally administered topical 5-aminosalicylate or corticosteroids within 4 weeksprior to screening

• Received therapeutic enema or suppository, other than required for colonoscopy orflexible sigmoidoscopy within 4 weeks prior to screening or during screening

• Antibiotics for ulcerative colitis or gastrointestinal infection within 4 weeks priorto screening

• Patient who has previously participated in any clinical trial of GBR500 / SAR339658

• Patient who has taken other investigational medications within 2 months or 5 halflives, (whichever is longer) prior to screening

• Use of any biologics for the treatment of ulcerative colitis in the previous 8 weeksbefore screening

• Requirement for concomitant treatment that could bias primary evaluation

• Pregnant or breast-feeding women

• Women of childbearing potential not protected by highly effective contraceptive methodof birth control

• Patient with latent or active tuberculosis (TB) defined as:

• Any signs or symptoms suggestive of active TB upon medical history or clinicalexamination

• Patients with a positive QuantiFERON TB Gold Test

• Chest radiograph within 3 months prior to the inclusion visit consistent withprior tuberculosis infection including, but not limited to, apical scarring,apical fibrosis, or multiple calcified granulomasa. This does not includenon-caseating granulomasa

• Patients with close contact with a person with active tuberculosis

• Patient with a history of listeriosis or tuberculosis (unless it is documented thatthey were adequately treated)

• Administration of any live (attenuated) vaccine within 3 months prior to the screeningVisit (eg, varicella-zoster vaccine, oral polio, rabies)

• Positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis B core antibody (HBcAb); and/or positive Hepatitis C antibody (HCV) at the Screening Visit

• Prior opportunistic infections within 6 months prior to screening or while receivinganti-TNF treatment

• History of a hypersensitivity reaction, other than localized injection site reaction,to any biological molecule

• History or any current signs of demyelinating disease or any neurological disease thatcan by the opinion of Investigator interfere with study safety assessments includingassessment for progressive multifocal leukoencephalopathy

• Patients with bleeding disorders or known platelet dysfunction The above information is not intended to contain all considerations relevant to a patient'spotential participation in a clinical trial.