E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009900 |
E.1.2 | Term | Colitis ulcerative |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of SAR339658 |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of SAR339658 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
o Male or Female ≥18 and ≤70 years old
o History of active ulcerative colitis of at least 3 months duration
o Active UC should be confirmed by colonoscopy or flexible sigmoidoscopy during the screening period within 7 days prior to randomization.
o 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-TNFs:
o 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
o TNF-alpha antagonists: Patient must have had an inadequate response or lost response or be intolerant to TNF-alpha antagonists
o Fecal calprotectin ≥200mg/kg
o Patients on corticosteroids must be on a stable dose ≥2 weeks prior to screening
o 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
o Patients on oral 5-aminosalicylates, mesalamine or sulfasalazine must be on a stable dose for ≥4 weeks prior to screening
o Patients naïve to anti-TNF alpha or non responder (primary or secondary) or intolerant to anti-TNF alpha
o Signed written informed consent
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E.4 | Principal exclusion criteria |
o Patients with Crohn's Disease (CD)
o Diagnosis of indeterminate colitis
o 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.
o Patients with prior colectomy or anticipated colectomy during their participation in the study
o Presence of ileal pouch or ostomy
o Fulminant disease or toxic megacolon
o Colonic dysplasia except for adenoma
o Total Parenteral Nutrition (TPN)
o Cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide or tacrolimus within 2 months prior to screening
o Previous exposure to natalizumab (Tysabri®) or vedolizumab
o Antidiarrheals within 2 weeks prior to screening
o Prednisone >40 mg/day (or equivalent)
o Budesonide >9 mg/day
o Received intravenous corticosteroids within 2 weeks prior to screening or during screening
o Rectally administered topical 5-aminosalicylate or corticosteroids within 4 weeks prior to screening
o Received therapeutic enema or suppository, other than required for colonoscopy or flexible sigmoidoscopy within 4 weeks prior to screening or during screening
o Antibiotics for UC or gastrointestinal infection within 4 weeks prior to screening
o Patient who has previously participated in any clinical trial of GBR500 / SAR339658
o Patient who has taken other investigational medications within 2 months or 5 half lives, (whichever is longer) prior to screening
o Use of any biologics for the treatment of UC in the previous 8 weeks before screening
o Requirement for concomitant treatment that could bias primary evaluation
o Pregnant or breast-feeding women
o Women of childbearing potential not protected by highly effective contraceptive method of birth control
o Patient with latent or active tuberculosis (TB)
o Any signs or symptoms suggestive of active TB upon medical history or clinical examination
o Patients with a positive QuantiFERON TB Gold Test (This test can be repeated once if indeterminate or believed to be a false positive)
o 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
o Patients with close contact with a person with active tuberculosis
o Patient with a history of listeriosis or tuberculosis (unless it is documented by a specialist that they were adequately treated previously or were given prophylactic treatment and can now start treatment with biologics)
o Administration of any live (attenuated) vaccine within 3 months prior to the screening Visit (eg, varicella-zoster vaccine, oral polio, rabies).
o Positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis B core antibody (HBcAb); and/or positive Hepatitis C antibody (HCV) at the Screening Visit.
o Prior opportunistic infections within six months prior to screening or while receiving anti-TNF treatment
o History of a hypersensitivity reaction, other than localized injection site reaction (ISR), to any biological molecule
o 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 PML
o Patients with bleeding disorders or known platelet dysfunction
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of Participants with Clinical Response by Mayo Score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Proportion of Participants with Clinical Remission by Mayo Score
Proportion of Participants with Mucosal Healing
Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ)
Change from Baseline in Quality of Life (QoL) SF-36
Change from Baseline in the partial Mayo Score
Number of Participants with adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At Week 8
At Week 8
At Weeks 4 and 8
At Weeks 4 and 8
At Weeks 4 and 6
Up to Week 18 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Canada |
France |
Germany |
Italy |
Poland |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |