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

Phase 2

Completed

• Conditions: Ulcerative Colitis
• Interventions: Drug: Placebo; Drug: cobitolimod

• Registration Number: NCT03178669
• Lead Sponsor: InDex Pharmaceuticals

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).

Study Timeline

• Study First Submitted: 2017-06-05
• Study First Submitted QC: 2017-06-05
• Study First Posted: 2017-06-07
• Study Start: 2017-06-21
• Primary Completion: 2019-08-30
• Study Completion: 2019-08-30
• Results First Submitted: 2020-11-13
• Status Verified: 2021-01
• Results First Submitted QC: 2021-01-12
• Last Update Submitted: 2021-01-12
• Results First Posted: 2021-02-01
• Last Update Posted: 2021-02-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 213

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo at four occasions
Cobitolimod Dose 4x125 mg	cobitolimod	Dose 125 mg of cobitolimod, at 4 occasions
Cobitolimod Dose 2x31 mg	cobitolimod	Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions
Cobitolimod Dose 2x125 mg	cobitolimod	Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions
Cobitolimod Dose 2x250 mg	cobitolimod	Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

Primary Outcome Measures

Name	Time	Method
Clinical Remission	6 weeks after first treatment	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).

Secondary Outcome Measures

Name	Time	Method
Modified Clinical Remission	Week 6	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
Symptomatic Remission	Week 6	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)
Clinical Response	Week 6	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)
Endoscopic Remission	Week 6	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)
Histological Remission	Week 6	Patients with histological remission at Week 6 (yes=1, no=0), defined by the Nancy histological index of grade 0 or 1

Trial Locations

Locations (62)

1; 🇨🇿 Prague, Czechia

2; 🇫🇷 Amiens, France

3; 🇫🇷 Caen, France

4; 🇫🇷 Clichy, France

5; 🇫🇷 Grenoble, France

6; 🇫🇷 Nice, France

7; 🇫🇷 Pierre-Bénite, France

8; 🇫🇷 Saint-Étienne, France

9; 🇫🇷 Toulouse, France

10; 🇫🇷 Vandœuvre-lès-Nancy, France

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