DiaMedica Therapeutics’ Phase II/III ReMEDy2 clinical trial of DM199 for treating patients with acute ischemic stroke (AIS) was placed on hold by the US Food and Drug Administration (FDA).
DM199 is a recombinant (synthetic) form of human tissue kallikrein-1 (KLK1), a serine protease (protein).
The adaptive design, double-blind, randomised, placebo-controlled ReMEDy2 trial is assessing DM199 to treat AIS patients.
The latest move comes after the company halted subject enrolment and submitted three serious adverse event reports to the regulatory agency linked to clinically significant, transient hypotension or low blood pressure happening soon after dosing with intravenous (IV) DM199.
Within minutes after stopping the IV infusion, the blood pressure levels of these patients went back to their baseline levels, DiaMedica noted.
The company considers that the adverse events in the ReMEDy2 trial were due to switching to an IV bag formulated from various materials as against those utilised in the prior Phase II ReMEDy1 trial.
A different kind of IV bag was used in the ReMEDy2 trial following necessary compatibility testing since those utilised in the ReMEDy1 trial were not available in many hospitals in the US owing to supply issues.
As part of the analysis of the events that caused these hypotensive events, DiaMedica is checking the variations in drug absorption in the IV bags used in both trials.
Furthermore, the company intends to hold talks with the FDA to update the ReMEDy2 trial protocol to modify the DM199 IV dosing in line with the ReMEDy1 trial considering these variations.
The company has to submit the assessment of the events that led to or caused hypotension, trial protocol modifications to eliminate such events, and the rationale and supporting data for the modifications, to the regulatory agency.
These data are expected to be submitted on concluding the compatibility assessment.
Additional subject enrolment in the ReMEDy2 trial might be halted until FDA notifies the company to resume enrolment.
DiaMedica Therapeutics president and CEO Rick Pauls said: “While having to pause enrolment in the ReMEDy2 trial was not desirable, we remain confident about the future potential of DM199 and are committed to refining the dosing procedures and methods that will further enhance patient safety.
“We also take comfort in that the transient hypotension observed is yet another clinical indicator that DM199 may be biologically active in stroke patients and may provide a meaningful improvement in stroke outcomes.”