The Efficacy of Cobitolimod in Patients With Moderate to Severe Active Ulcerative Colitis (CONDUCT)

• ClinicalTrials.gov Identifier: NCT03178669
• Recruitment Status: Active, not recruiting
• First Posted: June 7, 2017
• Last Update Posted: August 6, 2019
• Sponsor: InDex Pharmaceuticals
• Information provided by (Responsible Party): InDex Pharmaceuticals

Study Description

Brief Summary:

The purpose of this study is to evaluate efficacy of cobitolimod treatment at different dose levels and frequencies compared to placebo in patients with moderate to severe active ulcerative colitis.

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis	Drug: cobitolimod; Drug: Placebo	Phase 2

Detailed Description:

This is a Phase 2b study in patients with moderate to severe active ulcerative colitis. Patients will either receive cobitolimod dose A, B or C at two occasions or dose B or placebo at four occasions. To ensure blindness patients receiving active treatment at two occasions will receive placebo at the other two occasions. Blood, stool, and tissue samples will be collected at various time points throughout the study to evaluate safety and efficacy.

Duration of participation for patients will be approximately 12 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 213 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised Dose-Optimisation Study to Evaluate the Efficacy and Safety of Cobitolimod in Moderate to Severe Active Ulcerative Colitis Patients
• Actual Study Start Date: June 21, 2017
• Estimated Primary Completion Date: September 2019
• Estimated Study Completion Date: September 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cobitolimod Dose 31 mg x 2; Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions	Drug: cobitolimod; Rectal administration; Other Name: Kappaproct
Experimental: Cobitolimod Dose 125 mg x 2; Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions	Drug: cobitolimod; Rectal administration; Other Name: Kappaproct
Experimental: Cobitolimod Dose 250 mg x 2; Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions	Drug: cobitolimod; Rectal administration; Other Name: Kappaproct
Experimental: Cobitolimod Dose 125 mg x 4; Dose 125 mg of cobitolimod, at 4 occasions	Drug: cobitolimod; Rectal administration; Other Name: Kappaproct
Placebo Comparator: Placebo; Placebo at four occasions	Drug: Placebo; Solution manufactured to mimic cobitolimod; Other Name: Placebo (for cobitolimod)

Outcome Measures

Primary Outcome Measures :

1. Clinical Remission [ Time Frame: 6 weeks after first treatment ]
   defined by Modified Mayo sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, and iii) endoscopy score of 0 or 1 (excluding friability)

Secondary Outcome Measures :

1. Symptomatic Remission [ Time Frame: Week 4 and Week 6 ]
   defined by the Mayo sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, (patient reported outcome) [PRO2]
2. Abscence of rectal bleeding [ Time Frame: Week 4 and Week 6 ]
   defined by the Mayo sub score rectal bleeding of 0
3. Normal or enhanced stool frequency [ Time Frame: Week 4 and Week 6 ]
   defined by the Mayo sub score stool frequency of 0 or 1 (with at least one point decrease from Baseline)
4. Endoscopic Remission [ Time Frame: Week 6 ]
   defined by the Modified Mayo endoscopic sub score of 0 or 1 (excluding friability)
5. Histological Remission [ Time Frame: Week 6 ]
   defined by the Nancy histological index
6. Histological Response [ Time Frame: Week 6 ]
   defined by the Nancy histological index score
7. Modified Clinical Remission [ Time Frame: Week 6 ]
   defined by the Modified Mayo score ≤ 2 and sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline), iii) endoscopy score of 0 or 1 (excluding friability ) and iiii) physician´s global assessment (PGA) of 0 or 1
8. Clinical Response [ Time Frame: Week 6 ]
   defined as clinical remission or a three point and ≥ 30% decrease from Baseline.
9. Change in faecal calprotectin [ Time Frame: Week 1,2, 3 and 6 ]
   defined as a mean change compared to Baseline
10. Change in the inflammatory bowel disease questionnaire (IBDQ) [ Time Frame: Week 6 ]
    defined as mean change compared to Baseline

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 18 years old
• Established diagnosis of UC
• Moderately to severely active left sided UC assessed by central reading
• Current oral 5-ASA/SP use or a history of oral 5-ASA/SP use
• Current GCS use or history of GCS dependency, refractory, or intolerance

• Demonstrated an inadequate response, loss of response, or intolerance to at least one of the following agents:

  • Immunomodulators
  • TNF-α inhibitors and/or anti-integrins

Exclusion Criteria:

• Suspicion of differential diagnosis
• Acute fulminant UC and/or signs of systemic toxicity
• UC limited to the rectum (disease which extend <15 cm above the anal verge)
• History of malignancy
• History or presence of any clinically significant disorder
• Concomitant treatment with cyclosporine, methotrexate, tacrolimus, TNF-α inhibitors, anti-integrins or similar immunosuppressants and immunomodulators
• Treatment with rectal GCS, 5-ASA/SP or tacrolimus
• Long term treatment with antibiotics or non-steroidal anti-inflammatory drugs (NSAIDs)
• Serious active infection
• Gastrointestinal infections
• Currently receiving parenteral nutrition or blood transfusions
• Females who are lactating or have a positive serum pregnancy test
• Women of childbearing potential not using reliable contraceptive methods
• Concurrent participation in another clinical study
• Previous exposure to cobitolimod

Contacts and Locations

  Show 64 Study Locations

Sponsors and Collaborators

InDex Pharmaceuticals

Investigators

• Principal Investigator: Raja Atreya; Friedrich-Alexander University Erlangen-Nuremberg

More Information

• Responsible Party: InDex Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03178669 History of Changes
• Other Study ID Numbers: CSUC-01/16; 2016-004217-26 ( EudraCT Number )
• First Posted: June 7, 2017
• Last Update Posted: August 6, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by InDex Pharmaceuticals:

Colitis, Ulcerative; Gastrointestinal Diseases; Inflammatory Bowel Disease; Immunomodulator Therapy; Glucocorticoids; Anti-Inflammatory Agents; Therapeutic uses; Kappaproct; IDX0150; DIMS0150

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases