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

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

Primary Objective:

To assess the efficacy of SAR339658

Secondary Objective:

To assess the safety of SAR339658

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: SAR339658; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Investigational Site Number 040003
• Canada
  • Vancouver, Canada, V6Z 2K5
    • Investigational Site Number 124002
• France
  • Grenoble, France, 38043
    • Investigational Site Number 250003
  • Vandoeuvre Les Nancy, France, 54511
    • Investigational Site Number 250006
• Germany
  • Berlin, Germany, 14163
    • Investigational Site Number 276001
  • Hamburg, Germany, 20246
    • Investigational Site Number 276007
  • Hamburg, Germany, 79106
    • Investigational Site Number 276005
• Italy
  • Firenze, Italy, 50141
    • Investigational Site Number 380003
  • San Giovanni Rotondo, Italy, 71013
    • Investigational Site Number 380006
• Poland
  • Gdynia, Poland, 81-969
    • Investigational Site Number 616001
  • Lodz, Poland, 90-242
    • Investigational Site Number 616004
  • Lodz, Poland, 90-302
    • Investigational Site Number 616005
  • Lodz, Poland, 90302
    • Investigational Site Number 616002
  • Poznan, Poland, 60539
    • Investigational Site Number 616007
  • Sroda Wielkopolska, Poland, 63-000
    • Investigational Site Number 616006
  • Warszawa, Poland, 03-580
    • Investigational Site Number 616008
• United States
  • Arizona
    • Sun City, Arizona, United States, 85351
      • Investigational Site Number 840065
  • California
    • Mission Hills, California, United States, 91345
      • Investigational Site Number 840059
    • San Diego, California, United States, 92114
      • Investigational Site Number 840074
  • Colorado
    • Littleton, Colorado, United States, 80120
      • Investigational Site Number 840061
  • Florida
    • Miami, Florida, United States, 33136
      • Investigational Site Number 840003
    • Miramar,, Florida, United States, 33025
      • Investigational Site Number 840008
    • Winter Park,, Florida, United States, 32789
      • Investigational Site Number 840048
  • Georgia
    • Savannah,, Georgia, United States, 31405
      • Investigational Site Number 840053
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Investigational Site Number 840001
    • Oak Lawn, Illinois, United States, 60453
      • Investigational Site Number 840005
  • Louisiana
    • Hammond, Louisiana, United States, 70403
      • Investigational Site Number 840078
  • Michigan
    • Rochester Hills, Michigan, United States, 48098
      • Investigational Site Number 840070
  • Mississippi
    • Ocean Springs, Mississippi, United States, 39564
      • Investigational Site Number 840060
  • Missouri
    • Mexico, Missouri, United States, 65265
      • Investigational Site Number 840024
  • New York
    • Great Neck, New York, United States, 11021
      • Investigational Site Number 840051
    • Rochester, New York, United States, 14642
      • Investigational Site Number 840071
  • North Carolina
    • Winston Salem, North Carolina, United States, 27157-1071
      • Investigational Site Number 840089
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Investigational Site Number 840046
  • Pennsylvania
    • Phoenixville, Pennsylvania, United States, 19460
      • Investigational Site Number 840045
  • Texas
    • Pasadena,, Texas, United States, 77505
      • Investigational Site Number 840019
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 840088
    • Sugar Land, Texas, United States, 77479
      • Investigational Site Number 840038
  • Virginia
    • Charlottesville,, Virginia, United States, 22908
      • Investigational Site Number 840068
  • Washington
    • Seattle, Washington, United States, 98104-2499
      • Investigational Site Number 840034
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Investigational Site Number 840064

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: August 3, 2012
• First Submitted That Met QC Criteria: August 3, 2012
• First Posted (Estimate): August 7, 2012

Study Record Updates

• Last Update Posted (Estimate): July 13, 2016
• Last Update Submitted That Met QC Criteria: July 12, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: ACT12688; 2012-002013-19 (EudraCT Number); U1111-1124-1076 (Other Identifier: UTN)