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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to evaluate efficacy of cobitolimod treatment at different dose levels and frequencies compared to placebo in patients with moderate to severe left-sided ulcerative colitis.

Detailed Description
-----------------
This was a Phase IIb study in patients with moderate to severe left-sided ulcerative colitis. Patients either received cobitolimod 31 mg, 125 mg or 250 mg at two occasions or 125 mg or placebo at four occasions during a 3-weeks period. To ensure blindness, patients received active treatment at two occasions and placebo at the other two occasions. Blood, stool, and tissue samples was collected at various time points throughout the study to evaluate safety and efficacy. Primary endpoint was evaluated at week 6. Duration of participation for patients was approximately 12 weeks (from screening to final follow-up visit).

Official Title
-----------------
A Randomised Dose-Optimisation Study to Evaluate the Efficacy and Safety of Cobitolimod in Moderate to Severe Active Ulcerative Colitis Patients

Conditions
-----------------
Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: cobitolimod
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years old Established diagnosis of Ulcerative Colitis (UC) Moderately to severely active left sided UC assessed by central reading Current oral 5-Aminosalicylic Acid (5-ASA)/ Sulphasalazine (SP) use or a history of oral 5-ASA/SP use Current Glucocorticosteroids (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 Tumor Necrosis Factor alpha (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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cobitolimod Dose 2x31 mg<br>Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions | Drug: cobitolimod<br>* Rectal administration<br>* Other names: Kappaproct;|
| Experimental: Cobitolimod Dose 2x125 mg<br>Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions | Drug: cobitolimod<br>* Rectal administration<br>* Other names: Kappaproct;|
| Experimental: Cobitolimod Dose 2x250 mg<br>Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions | Drug: cobitolimod<br>* Rectal administration<br>* Other names: Kappaproct;|
| Experimental: Cobitolimod Dose 4x125 mg<br>Dose 125 mg of cobitolimod, at 4 occasions | Drug: cobitolimod<br>* Rectal administration<br>* Other names: Kappaproct;|
| Placebo Comparator: Placebo<br>Placebo at four occasions | Drug: Placebo<br>* Solution manufactured to mimic cobitolimod<br>* Other names: Placebo (for cobitolimod);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission | Patients with clinical remission at Week 6 (yes=1, no=0), 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, Week 0), and iii) endoscopy score of 0 or 1 (excluding friability). | 6 weeks after first treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Clinical Remission | Patients with modified clinical remission at Week 6 (yes=1, no=0), 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, Week 0), iii) endoscopy score of 0 or 1 (excluding friability ) and iiii) physician´s global assessment (PGA) of 0 or 1 | Week 6 | 
| Symptomatic Remission | Patients with symptomatic remission at Week 6 (yes=1, no=0), 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, Week 0), (patient reported outcome) | Week 6 | 
| Clinical Response | Patients with clinical response at Week 6 (yes=1, no=0), defined as clinical remission or a three point and ≥30 % decrease from Baseline, Week 0 in the sum of the Modified Mayo score, i) rectal bleeding, ii) stool frequency and iii) endoscopy score (excluding friability), iiii) physicians global assessment (PGA) | Week 6 | 
| Endoscopic Remission | Patients with endoscopic remission at Week 6 (yes=1, no=0), defined by the Modified Mayo endoscopic sub score of 0 or 1 (excluding friability) | Week 6 | 
| Histological Remission | Patients with histological remission at Week 6 (yes=1, no=0), defined by the Nancy histological index of grade 0 or 1 | Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IDX0150, DIMS0150, Colitis, Ulcerative, Gastrointestinal Diseases, Inflammatory Bowel Disease, Immunomodulator Therapy, Glucocorticoids, Anti-Inflammatory Agents, Therapeutic uses, Kappaproct