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

Study Overview
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Brief Summary
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Primary Objective: To assess the efficacy of SAR339658 Secondary Objective: To assess the safety of SAR339658

Detailed Description
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating Efficacy and Safety of SAR339658 in Patients With Active Moderate to Severe Ulcerative Colitis (UC)

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: SAR339658
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR339658<br>SAR339658 at Weeks 0, 2, 4, and 6 | Drug: SAR339658<br>* Pharmaceutical form:solution for infusion Route of administration: intravenous<br>* Other names: Vatelizumab;|
| Placebo Comparator: Placebo<br>Placebo at Weeks 0, 2, 4, and 6 | Other: Placebo<br>* Pharmaceutical form: solution for infusion Route of administration: intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with Clinical Response by Mayo Score |  | At Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with Clinical Remission by Mayo Score |  | At Week 8 | 
| Proportion of Participants with Mucosal Healing |  | At Week 8 | 
| Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) |  | At Weeks 4 and 8 | 
| Change from Baseline in Quality of Life (QoL) SF-36 |  | At Weeks 4 and 8 | 
| Change from Baseline in the partial Mayo Score |  | At Weeks 4 and 6 | 
| Number of Participants with adverse events |  | Up to Week 17 |