The trial is a twin of ENSURE-1, which began in November 2021, and is supported by positive clinical data from the phase 2 EMPhASIS trial.
The first patient has been enrolled in the phase 3 ENSURE-2 pivotal clinical trial of IMU-838, a dihydroorotate dehydrogenase inhibitor vidofludimus calcium, for the treatment of relapsing multiple sclerosis (RMS), Immunic recently announced. The trial is a twin of ENSURE-1 (NCT05134441), with both comprising the ENSURE program to evaluate the efficacy, safety, and tolerability of IMU-838.1
The FDA cleared an investigational new drug (IND) application for the phase 3 program in July 2021, and both trials are aimed at providing additional reliable data with the potential to speed up regulatory IND approval. In ENSURE-1, which began in November 2021, and ENSURE-2, 30-mg daily doses of IMU-838 are compared with placebo in patients with RMS, enrolling a combined total of 1050 adult participants at over 100 sites in 15 countries.
The primary end point is cited as time to first relapse up to 72 weeks. Secondary end points are noted as volume of T2-lesions, time to confirmed disability progression, time to sustained clinically relevant change sin cognition, and percentage of whole brain volume change, grey matter volume, and white matter volume.
“The phase 3 program’s trial design has been approved by many ethics committees and regulators, validating Immunic’s approach,” Andreas Muehler, MD, chief medical officer, Immunic, said in a statement.1 “The ENSURE program, along with the supportive phase 2 CALLIPER trial in progressive multiple sclerosis, designed to corroborate the neuroprotective potential of vidofludimus calcium and back its differentiated profile, gives us a strong foundation from which we hope to ultimately position the drug as a preferred oral therapeutic option that allows MS patients to continue their normal social lives without being reminded that they are on a chronic treatment.”
The trials are supported by positive clinical data from the phase 2 EMPhASIS trial (NCT03846219), which suggested that IMU-838 had a placebo-like safety profile, as well as robust anti-inflammatory and neuroprotective properties. Topline results from that study presented at the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22, showed that the drug reduced combined unique active MRI lesions in patients with RMS.2
The EMPhASIS trial further found participants treated with IMU-838 had an absence of hepatoxicity signals and relevant adverse events, when compared with other oral base medications commercially available for RMS treatment. Also demonstrated was a decrease in serum neurofilament light change, demonstrating its potential neuroprotective activity.1,2
A separate IND application for the supportive phase 2 CALLIPER trial (NCT05054140) was cleared in July 2021 as well. The trial is a multicenter, randomized, double-blind, placebo-controlled phase 2 trial that will run concurrently with the phase 3 ENSURE program, enrolling a total of 450 patients with progressive MS at over 70 sites. Patients will be randomized to either 45-mg daily doses of IMU-838 or placebo for up to 120 weeks. Investigators will then use annualized rate of percent brain volume change as the primary end point, while secondary end points include annualized rate of change in whole brain atrophy, as well as time to 24-week confirmed disability progression, based on the Expanded Disability Status Scale. The first patient was enrolled in September 2021.3
“Based on the strong activity observed in our phase 2 EMPhASIS trial and the drug’s well-established safety and tolerability profile to date, we believe that the design of the ENSURE program provides a straightforward path towards potential regulatory approval of vidofludimus calcium in RMS,” Daniel Vitt, PhD, CEO and president, Immunic, said in a statement.1
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