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A Randomised Double-Blind Placebo-Controlled Phase III Clinical 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

Phase 3
Conditions
inflammatory bowel disease
chronic inflammation of the lining of the colon
Ulcerative Colitis
Registration Number
NL-OMON51406
Lead Sponsor
InDex Pharmaceuticals AB
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Pending
Sex
Not specified
Target Recruitment
5
Inclusion Criteria

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.

Exclusion Criteria

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 w

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Primary Efficacy Endpoint: Induction Study<br /><br>Proportion of participants with clinical remission at I-week 6, defined by the<br /><br>3-component Mayo score, i) rectal bleeding of 0, ii) stool frequency of 0 or 1<br /><br>(with at least one (1) point decrease from I-week 0 if 1 at I-week 0), and iii)<br /><br>endoscopic score of 0 or 1.<br /><br><br /><br>Primary Efficacy Endpoint: Maintenance Study<br /><br>Proportion of participants with clinical remission at M-week 45, defined by the<br /><br>3-component Mayo score, i) rectal bleeding of 0, ii) stool frequency of 0 or 1<br /><br>(with at least one (1) point decrease from I-week 0 if 1 at I-week 0), and iii)<br /><br>endoscopic score of 0 or 1.</p><br>
Secondary Outcome Measures
NameTimeMethod
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