The Efficacy of Cobitolimod in Patients With Moderate to Severe Active Ulcerative Colitis
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 213
-
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
- 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)
34
🇷🇺Cheboksary, Russian Federation
53
🇺🇦Dnipropetrovs'k, Ukraine
56
🇺🇦Kiev, Ukraine
6
🇫🇷Nice, France
12
🇩🇪Berlin, Germany
2
🇫🇷Amiens, France
20
🇩🇪München, Germany
17
🇩🇪Leipzig, Germany
14
🇩🇪Hamburg, Germany
5
🇫🇷Grenoble, France
13
🇩🇪Erlangen, Germany
16
🇩🇪Heidelberg, Germany
21
🇭🇺Budapest, Hungary
11
🇩🇪Augsburg, Germany
27
🇵🇱Kraków, Poland
31
🇵🇱Sopot, Poland
24
🇭🇺Mosonmagyarovar, Hungary
55
🇺🇦Kharkiv, Ukraine
45
🇷🇸Belgrad, Serbia
1
🇨🇿Prague, Czechia
3
🇫🇷Caen, France
7
🇫🇷Pierre-Bénite, France
15
🇩🇪Hanover, Germany
8
🇫🇷Saint-Étienne, France
10
🇫🇷Vandœuvre-lès-Nancy, France
22
🇭🇺Békéscsaba, Hungary
23
🇭🇺Debrecen, Hungary
18
🇩🇪Lüneburg, Germany
19
🇩🇪Mannheim, Germany
32
🇵🇱Włocławek, Poland
25
🇭🇺Pécs, Hungary
26
🇵🇱Czestochowa, Poland
30
🇵🇱Poznań, Poland
28
🇵🇱Ksawerów, Poland
29
🇵🇱Lublin, Poland
35
🇷🇺Ekaterinburg, Russian Federation
33
🇵🇱Łódź, Poland
37
🇷🇺Kirov, Russian Federation
39
🇷🇺Novosibirsk, Russian Federation
40
🇷🇺Ryazan', Russian Federation
41
🇷🇺Saint Petersburg, Russian Federation
43
🇷🇺Tver, Russian Federation
42
🇷🇺Stavropol', Russian Federation
44
🇷🇺Ufa, Russian Federation
57
🇺🇦Luts'k, Ukraine
46
🇪🇸Ferrol, Spain
47
🇪🇸Fuenlabrada, Spain
48
🇪🇸Madrid, Spain
49
🇪🇸Sevilla, Spain
50
🇪🇸Valencia, Spain
52
🇺🇦Chernivtsi, Ukraine
54
🇺🇦Ivano-Frankivs'k, Ukraine
51
🇸🇪Uppsala, Sweden
58
🇺🇦Lviv, Ukraine
59
🇺🇦Odesa, Ukraine
60
🇺🇦Sumy, Ukraine
61
🇺🇦Zaporizhzhya, Ukraine
62
🇺🇦Úzhgorod, Ukraine
38
🇷🇺Moscow, Russian Federation
4
🇫🇷Clichy, France
36
🇷🇺Kazan, Russian Federation
9
🇫🇷Toulouse, France