efficacy and safety of sar339658 in patients with moderate to severe ulcerative colitis

Conditions: Ulcerative Colitis

Summary: primary objective: to assess the efficacy of sar339658 secondary objective: to assess the safety of sar339658

the study period per patient will include up to 4 weeks screening, 8 weeks treatment, 6 weeks post treatment safety follow-up, followed by a long term safety follow-up performed in the form of a phone interview at 3, 6, 12, 18 and 24 months from the last administration of the study medication. after completion of the 8-week treatment phase, patients may be eligible to enter a long term safety study (lts12593) for active treatment with sar339658.

Eligibility criteria:
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 the screening period within 7 days prior to randomization. * 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-tumor necrosis factors (tnfs): * 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 * tnf-alpha antagonists: patient must have had an inadequate response or lost response 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 for at 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 stable dose for ≥4 weeks prior to screening * patients naïve to anti-tnf alpha or non-responder (primary or secondary) or intolerant to 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 for aerobic pathogens including: aeromonas, plesiomonas, shigella, yersinia, campylobacter and e. coli spp. or positive for clostridium difficile b toxin in stools. * patients with prior colectomy or anticipated colectomy during their participation in the 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 tacrolimus within 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 during screening * rectally administered topical 5-aminosalicylate or corticosteroids within 4 weeks prior to screening * received therapeutic enema or suppository, other than required for colonoscopy or flexible sigmoidoscopy within 4 weeks prior to screening or during screening * antibiotics for ulcerative colitis or gastrointestinal infection within 4 weeks prior to 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 half lives, (whichever is longer) prior to screening * use of any biologics for the treatment of ulcerative colitis in the previous 8 weeks before 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 method of birth control * patient with latent or active tuberculosis (tb) defined as: * any signs or symptoms suggestive of active tb upon medical history or clinical examination * patients with a positive quantiferon tb gold test * 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 * patients with close contact with a person with active tuberculosis * patient with a history of listeriosis or tuberculosis (unless it is documented that they were adequately treated) * administration of any live (attenuated) vaccine within 3 months prior to the screening visit (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 receiving anti-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 that can by the opinion of investigator interfere with study safety assessments including assessment 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's potential participation in a clinical trial.