This is a randomized, double-blind, placebo-controlled Phase 2/3 adaptive, multi-center study to evaluate the efficacy and safety of DM199 for the treatment of acute ischemic stroke. Participants with AIS will be randomized 1:1 to DM199 or placebo (placebo is normal saline given with the same route (IV or SC) volume and frequency as DM199 diluted into normal saline), administered as a single intravenous (IV) dose followed by a subcutaneous (SC) dose within 2-12 hours of IV dose completion and then 2 times per week up to Day 21. The duration of each individual's participation in the study will be approximately 90 days from the time of initial treatment to completion of all study activities. Figure 1 depicts the overall study design.~An interim analysis will be conducted at the end of Phase 2 of the study after approximately 144 patients complete their Day 90 assessments. Additional patients will continue to be enrolled while the database and interim statistical analysis are prepared for review. A Data Safety Monitoring Board (DSMB) will review the interim data for efficacy and safety to determine if the trial will proceed into Phase 3. The adaptive feature of the study includes a formal interim assessment of efficacy and the possibility for increasing the sample size. The study is initially planned to enroll an additional 220 patients in Phase 3 (N=364 total). If sample size re-estimation is deemed appropriate from the interim analysis, a maximum of 584 patients may be enrolled in Phase 3 (N=728 total). This adaptive design is (inferentially) seamless because it continues from Phase 2 to Phase 3 without pausing enrollment and because all (N=364 to 728 total) patients in the study will be included in the final statistical analysis.
This is a Phase 2/3 study evaluating the safety and efficacy of DM199 in treating participants presenting within 24 hours of Acute Ischemic Stroke (AIS) onset for whom fibrinolytics and/or a catheter-based procedure, mechanical thrombectomy (MT), are not medically appropriate or available due to constraints of clot location, comorbidity risks, and/or time from estimated onset of stroke. The double-blinded study will be randomized, placebo controlled at approximately 75 centers in the U.S.