Ulcerative Colitis
Conditions
Brief summary
Primary Objective: To assess the efficacy of SAR339658 Secondary Objective: To assess the safety of SAR339658
Detailed description
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.
Interventions
DRUGSAR339658
Pharmaceutical form:solution for infusion Route of administration: intravenous
OTHERPlacebo
Pharmaceutical form: solution for infusion Route of administration: intravenous
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Participants with Clinical Response by Mayo Score | At Week 8 |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Participants with Mucosal Healing | At Week 8 |
| Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) | At Weeks 4 and 8 |
| Proportion of Participants with Clinical Remission by Mayo Score | At Week 8 |
| Change from Baseline in the partial Mayo Score | At Weeks 4 and 6 |
| Number of Participants with adverse events | Up to Week 17 |
| Change from Baseline in Quality of Life (QoL) SF-36 | At Weeks 4 and 8 |
Countries
Austria, Canada, France, Germany, Italy, Poland, United States
Outcome results
None listed