InDex Pharmaceuticals is advancing cobitolimod further towards phase III following successful interactions with FDA and EMA. Read more here.
Below you will find more information about our earlier clinical studies evaluating cobitolimod in patients with ulcerative colitis.
Cobitolimod has achieved clinical proof-of-concept in moderate to severe active ulcerative colitis. Data from five placebo controlled clinical studies show that cobitolimod has a very favorable safety profile and statistically significant effects on the endpoints that are most relevant for the disease, both from a regulatory and clinical perspective.
The CONDUCT study
CONDUCT was a randomized, double-blind, placebo-controlled and exploratory phase IIb study to evaluate other doses and dose frequencies than investigated in previous studies with cobitolimod, in patients with left-sided moderate to severe ulcerative colitis who do not respond to conventional treatments. The study objective was to identify the dosing regimen for further development.
CONDUCT met its primary endpoint with an outstanding combination of efficacy and safety. More information on the CONDUCT study design and results are available here.
The COLLECT study
COLLECT was a double-blind, placebo-controlled, randomized clinical study in 131 patients with treatment refractory moderate to severe ulcerative colitis. Top-line data was released at the end of June 2014. The study was conducted in the Czech Republic, France, Germany, Hungary, Italy, Poland and the UK and aimed at assessing the efficacy and safety of cobitolimod compared to placebo in chronic active treatment refractory ulcerative colitis patients.
Patients were treated with two single rectal 30 mg doses of cobitolimod four weeks apart and then followed for a total of 12 months. The patients were allowed to take their usual ulcerative colitis medication during the study except for cyclosporin, tacrolimus, TNF-alpha inhibitors or similar immunomodulating drugs.
Cobitolimod demonstrated statistically significant improvement compared to placebo for the secondary endpoints:
- Symptomatic remission (blood in stool = 0, number of stools/week <35) at week 4 and 8,
- Registration remission (Rachmilewitz/CAI score of ≤4, and an endoscopic Mayo score of 0 or 1) at week 4
- Rate of colectomy by week 22.
The authorities currently consider the symptoms of blood in stool, stool frequency, and mucosal healing (endoscopic remission), to be the most important endpoints to show clinical efficacy to achieve market approval. Remission based on these three variables showed a significant improvement in the cobitolimod-treated group compared with placebo at week 4. The treatment effect seen was in line with or better than what approved biological drugs have shown in their phase III studies. Cobitolimod was well tolerated and no safety signals compared to the placebo group were evident.
An unexpectedly high proportion of patients in the placebo group achieved remission as defined by the primary endpoint (Rachmilewitz/CAI score≤4) at week 12, and the study showed no significant difference between treatment groups for the primary endpoint. However, this endpoint is no longer considered by regulatory authorities to be a relevant definition of remission.
Earlier clinical studies
- A pilot study in 11 patients with moderate to severe inflammatory bowel disease resulted in a clinical response to cobitolimod treatment after one week in over 70 percent of the patients. In addition, cobitolimod induced a sustained clinical response over 3 months and was safe and well tolerated.
- A phase II study including 151 patients with mild to moderate active ulcerative colitis evaluating four different dose levels of cobitolimod treatment confirmed the good safety and tolerability seen in the previous study. Although statistical significance was not achieved for the primary endpoint, a numerically higher proportion of patients in the higher dose groups achieved clinical remission compared to patients in the placebo group. The study showed that cobitolimod was well-tolerated without any serious side effects.
- A second phase II trial was conducted in 34 patients with moderate to severe ulcerative colitis, who did not respond to corticosteroid therapy. The study showed a positive effect in established disease markers such as blood in stool and histology. A higher proportion of the patients achieved clinical remission in the cobitolimod group compared to the placebo group, although the study was too small to show statistical significance for the primary endpoint. Cobitolimod was well tolerated and no differences in safety profile were noted compared to placebo.
- A compassionate use was performed in 14 patients elected to undergo colectomy. 86 percent of the patients experienced clinical response and 79 percent clinical remission at week 12. The rate of colectomy among the patients was less than 10 percent.
The experiences from the five completed clinical studies have shown that rectal administration of up to 250 mg of cobitolimod given twice three weeks apart is well tolerated. In the clinical studies, a total of 416 patients with inflammatory bowel disease have been treated with cobitolimod without any relevant differences observed in the safety profile between the patients who received active substance and those who received placebo.