A Phase III Study to Evaluate the Efficacy and Safety of Cobitolimod as an Induction and Maintenance Therapy in Participants with Moderate to Severe Active Left-Sided Ulcerative Colitis
- Conditions
- Moderate to Severe left-sided Active Ulcerative ColitisMedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2021-002549-13-HU
- Lead Sponsor
- InDex Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 440
Inclusion Criteria: Induction
1. Male or female = 18 years of age.
2. Established diagnosis of UC, with minimum time from diagnosis of at least 3 months before screening visit 1b.
3. Moderate to severe active left-sided UC (disease should extend 15 cm or more above the anal verge and not beyond the splenic flexure) determined by a 3-component Mayo score of 5 to 9 with an endoscopic subscore =2 (in sigmoid or descending segments) assessed by central reading of endoscopy, and with stool frequency and rectal bleeding subscores, assessed by eDiary, each =1.
4. Have inadequate response, loss of response or be intolerant of at least one of the following treatments:
a. Oral GCS
b. AZA/6-MP
c. Biologics, JAK-inhibitors, or other approved advanced therapies for UC
5. Allowed to receive a therapeutic dose of the following UC drugs during the study:
a. Oral GCS therapy (=20 mg prednisone or equivalent/day) provided that the dose has been stable for 2 weeks prior to visit 1b, or oral Budesonide MMX® therapy (9 mg/day) initiated at least 8 weeks before visit 1b, provided that the dose has been stable for 2 weeks prior to visit 1b.
b. Oral 5-ASA/SP compounds, provided that the dose has been stable for 2 weeks prior to visit 1b and initiated at least 8 weeks before visit 1b.
c. AZA/6-MP provided that the dose has been stable for 8 weeks prior to visit 1b and initiated at least 3 months before visit 1b.
6. Ability to understand the treatment, willingness to comply with all study requirements, and ability to provide informed consent.
Inclusion Criteria: Maintenance
Participants are eligible to be included in the maintenance study if they have achieved clinical response at I-week 6 and have adhered to the protocol procedures of the induction study.
Clinical response is defined by a decrease in the 3-component Mayo score (rectal bleeding, stool frequency, and endoscopy) of at least two (2) points and at least 35% from I-week 0 with either a decrease in the rectal bleeding subscore of at least one (1) point or a rectal bleeding subscore of 0 or 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110
Exclusion Criteria: Induction
1. Suspicion of differential diagnosis such as Crohn’s enterocolitis, ischaemic colitis, radiation colitis, indeterminate colitis, infectious colitis, diverticular disease, associated colitis, microscopic colitis, massive pseudopolyposis or non-passable stenosis.
2. Acute fulminant UC, toxic megacolon and/or signs of systemic toxicity.
3. UC limited to the rectum (disease extending <15 cm above the anal verge) or extending beyond the splenic flexure.
4. Have failed treatment with more than three advanced therapies (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab or tofacitinib) of two different therapeutic classes (anti-TNF, anti-integrins, anti-IL12/23, JAKinhibitors, or other approved advanced therapies for UC).
5. Have had surgery for treatment of UC.
6. History of malignancy, unless treated with no relapse of the disease and = 5 years since last treatment (cured) or treated (cured) basal cell or squamous cell in situ carcinoma.
7. History or presence of any clinically significant disorder that, in the opinion of the investigator, could impact on the participant’s ability to adhere to the protocol and protocol procedures, or would confound the study result or compromise participant safety.
8. Concomitant treatment with cyclosporine, methotrexate, tacrolimus, or advanced therapies such as infliximab, adalimumab, golimumab, vedolizumab, ustekinumab or tofacitinib, or similar immunosuppressants and immunomodulators at enrolment.
Any prior treatment with such drugs must have been discontinued at least 8 weeks prior to visit 1b (except for ustekinumab, which must have been discontinued at least 12 weeks prior to visit 1 b) or have non-measurable serum concentration levels.
9. Treatment with rectal GCS, 5-ASA/SP or tacrolimus within 2 weeks before visit 1b.
10. Long-term treatment (>14 days) with antibiotics or NSAIDs within 2 weeks prior to visit 1b (one short treatment regimen for antibiotics, occasional use of NSAIDs and low dose NSAIDs as prophylactic therapy is allowed).
11. Serious known active infection including history of latent or active
tuberculosis, documented history of past or current tuberculosis, or living with or having frequent close contact with people with active tuberculosis or with a positive tuberculosis test according to current regulations for 12 weeks preceding randomisation. Serious infections include, but is not limited to, HIV, HBV, or HCV infections.
12. Gastrointestinal infections including positive Clostridium difficile stool assay. (Local laboratory reports must be available in accordance with normal clinic practice, to confirm that the current episode of disease exacerbation is not due to infection).
13. Females who are lactating or have a positive serum pregnancy test during the screening period.
14. Women of childbearing potential not using highly effective (failure rate < 1%) contraceptive methods throughout the duration of the study.
15. Concurrent participation in another clinical study with investigational therapy or previous use of investigational therapy within 5 half-lives and within at least 30 days after last treatment of the experimental product prior to enrolment.
16. Previous exposure to cobitolimod
Exclusion Criteria Maintenance:
Participants will not be eligible for the maintenance study if they are not willing to comply with all further study requirements.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method