dm+d

Unassigned

New Medicines

KappaproctRefractory ulcerative colitis (UC) - third-line

Information

Kappaproct
New molecular entity
InDex Pharmaceuticals
InDex Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase II Clinical Trials
Yes
Apr 20Index Pharmaceuticals announced it has received positive responses from FDA and EMA regarding phase III development of cobitolimod for the treatment of severe left-sided UC. This regulatory feedback gives flexibility for different designs of the PIII programme, and the company is continuing its PIII preparations, including efforts to secure financing
01. Dec 11: PIII study starts [1].
02. Orphan drug status in EU [2].
03. Mar 13: No further update
04. Apr 15: No further update, not listed on Almirall pipeline [4]
05. Mar 16: FDA clears the InDex application to initiate a PIIb study with cobitolimod in patients with moderate to severe UC [8].
06. Apr 17, InDex Pharmaceuticals initiated the phase IIb CONDUCT trial to evaluate the safety and efficacy of cobitolimod in patients with left-sided moderate to severe UC
07. Apr 18: The PII CONDUCT is evaluating higher doses and dose frequencies than investigated in previous studies with cobitolimod. The dose optimisation study investigates three different dose strengths of cobitolimod and two different dose frequencies. In parallel with the CONDUCT study, InDex is performing additional preclinical safety studies as preparation for PIII and has begun assessing the possibility to develop a capsule or tablet [12].

Category

DNA-based immunomodulatory sequence (DIMS) targeting the toll-like receptor 9 (TLR9) given intracolonically
UC has an annual incidence of 10 per 100,000 people , and a prevalence of 243 per 100,000. ~ 146,000 patients in the UK have a diagnosis of UC [3].
Refractory ulcerative colitis (UC) - third-line
Rectal

Trial or other data

01. Dec 11: NCT01493960 (COLLECT) A PIII placebo-controlled, double-blind, randomised study to assess the efficacy and safety of Kappaproct as an add-on to current practice in 120 patients with chronic active treatment refractory ulcerative colitis and who are potential candidates for colectomy.The primary outcome is the proportion of participants with induction of clinical remission at week 12, defined as a CAI score of ≤4, with subscores of blood in stool and number of stools weekly not exceeding 0 and 0 or 1, respectively. Kappaproct will be given as a 30mg rectal dose at weeks 0 and 4 [1].
02. Mar 12: Preliminary results from COLLECT expect Q1 2014 [2].
03. Apr 14: InDex and Admirall enter into a licence agreement for the European rights for Kappaproct. Results of the COLLECT study expected mid-2014 [4]
04. Jun 14: In the COLLECT study, Kappaproct improved rates of remission and reduced colectomy rates in patients with moderate to severe ulcerative colitis, when added to standard therapy [5].
05. Apr 15: No further update
06. Jun 15. InDex Pharmaceuticals terminates license agreement with Almirall and regains European rights to Kappaproct in ulcerative colitis. The next clinical study with Kappaproct® is currently being planned in discussion with EU and US regulatory agencies [7].
07. Mar 16: In the COLLECT study, Kappaproct demonstrated statistically significant effects on endpoints such as key clinical symptoms, i.e. blood in stool and number of stools, and mucosal healing (Mayo Endoscopy Score). A trend was also seen towards reduced rate of colectomy. The treatment effect was in line with best available third line treatments for UC. Kappaproct was well tolerated and no safety signals compared to the standard of care treatment group were evident. The primary endpoint, remission according to CAI, was not reached due to an unexpected high placebo response for this endpoint. The reasons for the high placebo response have been understood during the data analysis process, and can be avoided in future studies by optimizing efficacy parameters and time for measurements in line with current recomendations from the regulatory authorities [8].
08. Mar 16: The planned PIIb study will be a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of cobitolimod in inducing clinical remission in patients with chronic active moderate to severe ulcerative colitis as compared to placebo. The study will evaluate higher doses and more frequent dosing than those used in previous studies with the goal to provide substantially higher efficacy, while maintaining the compound’s superior safety profile [8].
09. Nov 16: PIII COLLECT study fully published . There was no statistical significant difference between the groups in the induction of clinical remission at Week 12, with 44.4% in the cobitolimod group vs. 46.5% in the placebo group. However, the proportion of patients who achieved symptomatic remission was 32.1% in the cobitolimod group vs. 14.0% in the placebo group at Week 4 (p=0.02), and 44.4% vs. 27.9% at Week 8 (p=0.06) [9]
10. Jan 18: PII CONDUCT study (NCT03178669) is still recruiting patients; collection of primary outcome data due to complete Dec 18 [11].