Clinical trial NCT01659138: Efficacy and Safety of SAR339658 in Patients With Moderate to Severe Ulcerative Colitis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating Efficacy and Safety of SAR339658 in Patients With Active Moderate to Severe Ulcerative Colitis (UC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ulcerative Colitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-08-07
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of Participants with Clinical Response by Mayo Score
timeFrame: At Week 8
Secondary outcomes:
measure: Proportion of Participants with Clinical Remission by Mayo Score
timeFrame: At Week 8
measure: Proportion of Participants with Mucosal Healing
timeFrame: At Week 8
measure: Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ)
timeFrame: At Weeks 4 and 8
measure: Change from Baseline in Quality of Life (QoL) SF-36
timeFrame: At Weeks 4 and 8
measure: Change from Baseline in the partial Mayo Score
timeFrame: At Weeks 4 and 6
measure: Number of Participants with adverse events
timeFrame: Up to Week 17
Other outcomes:
Locations:
city: Sun City
country: United States
facility: Investigational Site Number 840065
state: Arizona
city: Mission Hills
country: United States
facility: Investigational Site Number 840059
state: California
city: San Diego
country: United States
facility: Investigational Site Number 840074
state: California
city: Littleton
country: United States
facility: Investigational Site Number 840061
state: Colorado
city: Miami
country: United States
facility: Investigational Site Number 840003
state: Florida
city: Miramar,
country: United States
facility: Investigational Site Number 840008
state: Florida
city: Winter Park,
country: United States
facility: Investigational Site Number 840048
state: Florida
city: Savannah,
country: United States
facility: Investigational Site Number 840053
state: Georgia
city: Chicago
country: United States
facility: Investigational Site Number 840001
state: Illinois
city: Oak Lawn
country: United States
facility: Investigational Site Number 840005
state: Illinois
city: Hammond
country: United States
facility: Investigational Site Number 840078
state: Louisiana
city: Rochester Hills
country: United States
facility: Investigational Site Number 840070
state: Michigan
city: Ocean Springs
country: United States
facility: Investigational Site Number 840060
state: Mississippi
city: Mexico
country: United States
facility: Investigational Site Number 840024
state: Missouri
city: Great Neck
country: United States
facility: Investigational Site Number 840051
state: New York
city: Rochester
country: United States
facility: Investigational Site Number 840071
state: New York
city: Winston Salem
country: United States
facility: Investigational Site Number 840089
state: North Carolina
city: Cincinnati
country: United States
facility: Investigational Site Number 840046
state: Ohio
city: Phoenixville
country: United States
facility: Investigational Site Number 840045
state: Pennsylvania
city: Pasadena,
country: United States
facility: Investigational Site Number 840019
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 840088
state: Texas
city: Sugar Land
country: United States
facility: Investigational Site Number 840038
state: Texas
city: Charlottesville,
country: United States
facility: Investigational Site Number 840068
state: Virginia
city: Seattle
country: United States
facility: Investigational Site Number 840034
state: Washington
city: Wauwatosa
country: United States
facility: Investigational Site Number 840064
state: Wisconsin
city: Innsbruck
country: Austria
facility: Investigational Site Number 040003
city: Vancouver
country: Canada
facility: Investigational Site Number 124002
city: Grenoble
country: France
facility: Investigational Site Number 250003
city: Vandoeuvre Les Nancy
country: France
facility: Investigational Site Number 250006
city: Berlin
country: Germany
facility: Investigational Site Number 276001
city: Hamburg
country: Germany
facility: Investigational Site Number 276007
city: Hamburg
country: Germany
facility: Investigational Site Number 276005
city: Firenze
country: Italy
facility: Investigational Site Number 380003
city: San Giovanni Rotondo
country: Italy
facility: Investigational Site Number 380006
city: Gdynia
country: Poland
facility: Investigational Site Number 616001
city: Lodz
country: Poland
facility: Investigational Site Number 616004
city: Lodz
country: Poland
facility: Investigational Site Number 616005
city: Lodz
country: Poland
facility: Investigational Site Number 616002
city: Poznan
country: Poland
facility: Investigational Site Number 616007
city: Sroda Wielkopolska
country: Poland
facility: Investigational Site Number 616006
city: Warszawa
country: Poland
facility: Investigational Site Number 616008
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: