The ReMEDy2 trial is an adaptive design, randomized, double-blind, placebo-controlled trial studying the use of the Company’s product candidate, DM199, to treat acute ischemic stroke (AIS) patients. The trial is intended to enroll approximately 350 patients at 75 sites in the United States. Patients enrolled in the trial will be treated for three weeks with either DM199 or placebo, beginning within 24 hours of the onset of AIS symptoms, with the final follow-up at 90 days. The trial excludes patients treated with tissue plasminogen activator (tPA) and/or mechanical thrombectomy. The study population is representative of the approximately 80% of AIS patients who do not have treatment options today, primarily due to the limitations on treatment with tPA or mechanical thrombectomy. DiaMedica believes that the proposed trial has the potential to serve as a pivotal registration study of DM199 in this patient population. The trial follows DiaMedica’s previous ReMEDy1 clinical trial, a Phase 2 study which provided initial evidence that DM199 is safe, well tolerated and may improve physical recoveries, reduce the risk of stroke recurrence and reduce patient deaths in acute ischemic stroke patients whose stroke was caused by a blockage inside the brain (referred to as a small vessel occlusion) similar to the types of strokes being studied in the ReMEDy2 clinical trial.
The ReMEDy2 study is registered on Clinicaltrials.gov (NCT# 05065216). The FDA granted Fast Track Designation to DM199 for the treatment of AIS in September 2021. Fast Track is a process intended to facilitate the development and expedite the review of investigational drugs for the treatment of serious or life-threatening conditions where there is a significant unmet medical need.
Approximately 80% of acute ischemic stroke patients in the United States have no treatment option other than supportive care. Because of this significant unmet medical need, researchers are working hard to find new and better approaches to treat stroke patients. Advances in treatment are only possible through clinical research trials like ReMEDy2. A clinical trial is a medical research study to explore whether an investigational drug is safe and effective for humans. These trials require FDA approval in advance, are closely controlled and must follow strict scientific standards and regulatory requirements designed to protect patients and produce reliable results.
A clinical trial may find that a new investigational drug improves patient outcomes, offers no benefit, or causes unexpected harm. All these results are important because they advance medical knowledge and help improve patient care. Study physicians review risks and potential benefits with patients and their caregivers before patients are enrolled in any trial. All new drug candidates, like DM199, are studied in clinical trials to generate data that can be evaluated by the U.S. Food and Drug Administration (FDA), and other regulators, for safety and effectiveness before being approved for common use.
Subjects enrolled in the ReMEDy2 trial will be randomly assigned to be treated with either DM199 or placebo (normal saline 0.9%). Subjects will receive an intravenous (IV) dose within 24 hours of the onset of their stroke symptoms followed by a subcutaneous dose within 12 hours of the IV dose. Subjects will then receive two subcutaneous doses each week for three weeks. The study doctor will then arrange follow-up visits with the study subject at approximately 30 and 90 days after the participant’s stroke as part of closely monitoring the recovery of each study participant.
In order to scientifically assess the effects of DM199 in an unbiased way, neither the study participants nor the clinical team will know whether a participant receives DM199 or placebo.
The ReMEDy2 trial is designed to measure the level of patient physical recovery from acute ischemic stroke as of 90 days after the stroke, a time point consistently used in prior stroke studies. Physical recovery is measured using the well-established modified Rankin Scale (mRS), a standard scale for measuring the degree of disability or dependence in the patient’s daily activities. The degree of physical recovery is intended to evaluate the effectiveness of DM199. ReMEDy2 will also gather data on the safety of treatment with DM199.
DM199 is a recombinant (synthetic) form of a naturally occurring protein called human tissue kallikrein-1 (KLK1). KLK1 is produced primarily in the kidneys, as well as in the pancreas and salivary glands. KLK1, which is part of the Kallikrein-Kinin system, plays an important role in the regulation of local blood flow and vasodilation (the widening of blood vessels which decreases blood pressure) in the body, as well as an important role in mitigating inflammation and oxidative stress (an imbalance between potentially damaging reactive oxygen species, or free radicals, and antioxidants in the body). With age, the body’s ability to produce KLK1 may be reduced. KLK1 levels are often low in patients who have experienced a stroke and/or are at risk of a recurrent stroke. DiaMedica is the first company to have developed and clinically studied a pharmaceutically active synthetic form of the KLK1 protein.
DM199 is an investigational drug currently being studied in patients with acute ischemic stroke.
The safety and effectiveness of DM199 for the treatment of acute ischemic stroke has not been established and is limited to investigational use only.