Treatment of Acute Ischemic Stroke (ReMEDy2 Trial)
Purpose
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 up to approximately 100 sites.
Conditions
- Acute Stroke
- Ischemic Stroke
- Stroke
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Participant is ≥18 years of age. 2. Participant weight is 50 kg to 160 kg inclusive. 3. Participant to be randomized and treatment initiated within 24 hours of last known normal/AIS stroke onset. 4. Participant has NIHSS ≥5 and ≤ 15 at approximately the time of randomization. 5. Participant had a pre-morbid mRS score of 0 to 1 (mRS score prior to AIS) as stated by participant or participant's representative. 6. Participant and/or legally authorized representative is able to provide informed consent. 7. Participant is willing and able to comply with the study protocol, in the Investigator's judgment.
Exclusion Criteria
- Participant has any evidence of intracranial hemorrhage. 2. Participant has received or will receive fibrinolytics for their current AIS. 3. Participant has image findings with symptomatic large vessel occlusion at one or more of the following locations: Intracranial carotid I/T/L, M1 or M2 segment MCA, vertebral or basilar artery (BA). 4. Participant has large core of established infarction defined as ASPECTS 0-4. 5. Participant has or will receive MT for their current AIS. 6. Participant has imaging findings and/or symptoms consistent with a posterior circulation stroke. 7. Participant has any recorded SBP < 100 mm HG or MAP <65 mm Hg; MAP = DBP + [1/3 (SBP - DBP)] (measured with noninvasive BP cuff type monitor) after stroke symptom onset and prior to randomization. 8. Participant is currently prescribed angiotensin-converting enzyme inhibitor (ACEi) and is unable or unwilling to convert to another antihypertensive pharmacological treatment through Day 29 ±1 day (8 days after last treatment). 9. If participant is currently prescribed an ACEi and the last dose of the ACE inhibitor medication is reported to have been taken < 24 hours before start of IV study drug infusion as stated by participant or participant's representative. 10. Participant has a history of clinically significant allergic reactions such as angioedema or anaphylaxis requiring hospitalization. 11. Life expectancy estimated at ≤ 1 year prior to enrollment. 12. Participant has clinical evidence of an active infection at the time of enrollment requiring parenteral treatment or hospitalization to monitor or manage the infection. NOTE: Treatment of uncomplicated infections with oral antibiotics would not be an exclusion (example treatment of an uncomplicated urinary tract infections or sinus infections with oral antibiotics would not be an exclusion). 13. Participant has known alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency). 14. Participant is pregnant or nursing. NOTE: Participants who agree to stop nursing may be considered for inclusion at the discretion of the Investigator. 15. Participants of child-bearing potential must agree to use medically acceptable contraceptive measures to prevent pregnancy. All participants of childbearing potential (defined as sexually mature participants who have had menses within the preceding 24 months and have not undergone permanent sterilization methods such as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, etc.) must have a negative serum pregnancy test performed locally at screening. Participants of childbearing potential must agree not to attempt to become pregnant or undergo in vitro fertilization. If participating in sexual activity that could lead to pregnancy, participants must use 2 reliable methods (1 per partner is acceptable) of contraception simultaneously while receiving protocol-specified medication and during the study follow-up period. Participants participating in sexual activity must agree to use, or for their partner to use highly effective birth control methods (those with a failure rate of less than 1% per year when used consistently and correctly) until they have completed the study (after the Day 90 visit). Such methods include: - Combined (estrogen and progesterone containing) hormonal oral, intravaginal, or transdermal contraception associated with the inhibition of ovulation - Progesterone-only oral, injectable, or implantable hormonal contraception associated with the inhibition of ovulation - Intrauterine device (IUD) - Intrauterine hormone-releasing system (IUS) - Bilateral tubal occlusion - Vasectomized partner - Sexual abstinence Participants who are not of reproductive potential (who have been postmenopausal for more than 24 consecutive months or have undergone hysterectomy, bilateral oophorectomy) are not required to use contraception. Participants are prohibited from sperm donation. NOTE: A negative serum pregnancy test will be documented during screening if a participant is of child-bearing potential. 16. Participant is currently participating in or has participated in a study using an investigational device or drug or received an investigational drug or investigational use of a licensed drug within 30 days prior to screening. 17. Participant does not have sufficient venous access for infusion of study treatment or blood sampling. 18. Participant is unable or unwilling to comply with protocol requirements, including assessments, tests, and follow-up visits. 19. Participant has any other medical condition which in the opinion of the Investigator will make participation medically unsafe or interfere with the study results.
Study Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Phase 2/3 Adaptive Design, Randomized Double-blind Placebo-controlled Study to Evaluate the Safety and Efficacy of DM199 for the Treatment of Acute Ischemic Stroke (ReMEDy2 Trial)
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
- Masking Description
- To minimize bias, the participant and PI will be blinded to treatment assignment. All Sub-Investigators and other members of the study team will also remain blinded except for a designated unblinded pharmacist or designee responsible for compounding the assigned study treatment. The study team will remain blinded until all data is collected and database lock occurs.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental DM199 |
DM199 administered by a single intravenous (IV) dose followed by a subcutaneous (SC) dose within 12 hours and then 2 times a week for three weeks (until Day 21). |
|
|
Placebo Comparator Placebo |
Placebo administered by a single intravenous (IV) dose followed by a subcutaneous (SC) dose within 12 hours and then 2 times a week for three weeks (until Day 21). |
|
Recruiting Locations
Medstar Franklin Square Medical Center
Baltimore, Maryland 21237
Baltimore, Maryland 21237
More Details
- Status
- Recruiting
- Sponsor
- DiaMedica Therapeutics Inc
Detailed Description
This is a randomized, double-blind, placebo-controlled Phase 2/3 adaptive, multi-center study to evaluate the safety and efficacy 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), 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 for three weeks (until Day 21). After dosing is complete, participants will be followed up by the investigator at approximately 30 and 90 days after their first dose. A formal interim analysis will be conducted after 144 participants complete their Day 90 assessment in Part A. The purposes of this interim analysis are to assess safety, allow early stopping of the study for futility, or continuing the study with a revised final sample size of between 240 up to 728. The futility rule will be non-binding.