Interim Analysis Suggests Wider-than-expected Dosing Range for IMU-838 to Treat Ulcerative Colitis

Interim Analysis Suggests Wider-than-expected Dosing Range for IMU-838 to Treat Ulcerative Colitis

Interim analysis of a Phase 2 clinical trial that’s investigating IMU-838 in people with ulcerative colitis (UC) suggests a broader dose range than initially anticipated, announced the therapy’s developer, Immunic Therapeutics, in a news release.

IMU-838 is an orally available molecule that can inhibit the activity of immune cells called B and T cells. It is currently being investigated as a potential anti-inflammatory therapy for autoimmune diseases, including multiple sclerosis and UC, in an oral tablet formulation.

An ongoing Phase 2 clinical trial (NCT03341962), called CALDOSE-1, is evaluating IMU-838 in individuals with mild to severe UC. Participants are being treated with either IMU-838 or a placebo for the first phase of 10 to 22 weeks, followed by a second period of treatment (10 to 22 weeks), depending on the interim analysis. The primary objective is improvement, as assessed by patient-reported outcomes and endoscopy.

Three doses of IMU-838 are being tested: 10, 30, and 45 mg per day.

Immunic had predicted that 30 mg would be the lowest effective dose, based on preclinical data, but then added the 10 mg dose at the recommendation of the United States Food and Drug Administration.

The company had predicted — after about 60 participants had completed the 10-week induction treatment period — that the interim analysis would find the 10 mg dose not to be effective, and therefore that dosing arm would be discontinued.

An independent committee reviewed the very preliminary, unblinded data, and no statistical analyses were performed. The committee has also not revealed detailed data (to the public or the company) in order to protect the integrity of the ongoing blinded study.

Based on the available evidence, the committee concluded that the 10 mg dose appeared not to be ineffective, and the 45 mg dose was deemed not intolerable.

Subsequently, the trial’s steering committee voted to continue all three dosing arms of the trial, which will include an expansion of the total number of anticipated participants, from 195 to 240. Moreover, the company stated that these findings will impact the timeline for the trial, namely full patient enrolment and top-line data.

The interim dosing analysis and the conclusions made by the independent review committee may not reflect results of a final analysis of the trial once the full data set is analyzed, the company noted.

“While unexpected, we are very pleased to learn that even the lowest, 10 mg dose seems to show activity, suggesting that the potentially effective dose range for UC patients may be broader than previously thought,” Daniel Vitt, PhD, president and CEO of Immunic, said.

“Moreover, the knowledge that all three doses included in the CALDOSE-1 trial did not show unacceptable intolerance and are expected to be continued confirms the promising safety profile already established for IMU-838 in previous studies,” he added. “We look forward to continuing the study and reporting top-line data, when available.”