Acute Stroke, Ischemic Stroke, Stroke
Conditions
Keywords
acute, ischemic, stroke, AIS, tPA, LVO, MT, KLK1, Kallikreins
Brief summary
This is a Phase 2/3 study evaluating the safety and efficacy of DM199 (rinvecalinase alfa) in treating participants with moderate stroke severity, who present within 24 hours of Acute Ischemic Stroke (AIS) onset due to small and medium vessel occlusions. This study focuses on participants with limited treatment options. Participants who have or will receive mechanical thrombectomy (MT) are not eligible for participation. Additionally, participants who have received fibrinolytics are excluded unless they experience a persistent neurological deficit of moderate severity six or more hours after fibrinolytic treatment. Participants considered for this trial should not be denied the use of standard of care (SoC) AIS therapies, such as fibrinolytics or MT, when appropriate. The double-blinded study will be randomized and placebo-controlled at up to approximately 100 sites.
Detailed description
This is a 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). Participants with AIS will be randomized 1:1 to DM199 or placebo. DM199 will be administered as a single intravenous (IV) dose (0.5 μg/kg; not to exceed 50 μg) followed by subcutaneous (SC) doses at 2 hours (+10 hours) of the 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. A formal interim analysis will be conducted after 200 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 up to a maximum of 728 participants.
Interventions
DM199 administered by a single intravenous (IV) dose followed by subcutaneous (SC) doses at 2 hours (+10 hours) of the IV dose completion and then 2 times per week up to Day 21
OTHERPlacebo for DM199 Solution for Injection
Placebo administered by a single intravenous (IV) dose followed by subcutaneous (SC) doses at 2 hours (+10 hours) of the IV dose completion and then 2 times per week up to Day 21.
Sponsors
DiaMedica Therapeutics Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, 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. The study team will remain blinded until all data is collected, and database lock occurs.
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)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Participant is between 18 and 90 years of age inclusive. 2. Participant weight is 40 kg to 166 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. This criterion also applies to participants who meet the following conditions: * The participant initially presents with an NIHSS score below 5 but clinically worsens, including cases of progressing stroke / stroke-in-evolution, resulting in a subsequent persistent NIHSS score of ≥5 and ≤15; and * Participant meets all other inclusion and
Exclusion criteria
, including repeat brain imaging to rule out hemorrhagic transformation. 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. If participant has received fibrinolytic treatment for AIS within 4.5 hours of last know normal/AIS stoke onset and at least 6 hours after completing fibrinolytic treatment, and the participant meets all of the following criteria: * Participant's initial NIHSS score prior to fibrinolytics was ≤15; and * At least six hours after fibrinolytics, the participant has NIHSS score of ≥5 and ≤15 with a persistent deficit; and * The participant's NIHSS score showed less than a 4-point improvement, or worsened, after receiving fibrinolytics; and * Participant meets all other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stroke Recovery | Day 90 | Stroke recovery as defined by participants with excellent functional outcomes at Day 90 as assessed via the Modified Rankin Score (mRS \[dichotomized\]), mRS scores of 0 or 1 represent responders, scale range of 0-6. The mRS (Modified Rankin Scale) is a single-item, clinician-reported measure of functional disability in participants with AIS. Scores range in grade from 0 (no symptoms at all) to 6 (participant death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect on Disability | Day 90 | Assessment of effect on disability across the full spectrum of AIS by examining the distribution of mRS (shift) scores (scale range = 0 to 6) at Day 90. The mRS (Modified Rankin Scale) is a single-item, clinician-reported measure of functional disability in participants with AIS. Scores range in grade from 0 (no symptoms at all) to 6 (participant death). |
| Independent Function | Day 90 | Proportion of participants achieving independent function (able to look after their own affairs without assistance) with or without minor disability at Day 90 assessed as mRS 0-2 (dichotomized) mRS scores of 0, 1 or 2 represent responders, scale range of 0-6. The mRS (Modified Rankin Scale) is a single-item, clinician-reported measure of functional disability in participants with AIS. Scores range in grade from 0 (no symptoms at all) to 6 (participant death). |
| Mortality Rate | Day 90 | Mortality rate as defined by event rate (%) for mortality over 90 days. |
| Neurological Outcome | Day 90 | Proportion of participants achieving an excellent neurological outcome defined by National Institute of Health Stroke Scale (NIHSS)= 0-1 (dichotomized) (NIHSS scores of 0 or 1, scale range 0 to 42) at Day 90. The National Institute of Health Stroke Scale (NIHSS) is a clinician-reported measure used to rate the severity of strokes, namely disability and recovery after acute stroke. The scale is comprised of 11 items with item scores ranging from 0 to 4. Total scores range from 0 to 42, with higher scores indicating increased severity. |
| Functional Independence | Day 90 | Proportion of participants achieving an excellent functional independence in activities of daily living defined by Barthel Index score (dichotomized) greater than or equal to 5 (scale range 0 to 100) at Day 90. The Barthel Index (BI) is a 10-item scale assessing activities of daily living and functional disability. Each item is scored in increments of 5 points (0, 5, 10, or 15) and the individual items are summed to produce a total score between 0 and 100, with higher scores representing more optimal performance (100 = fully independent) and lower scores representing inferior performance (0 = totally dependent). |
| AIS Recurrence | Day 90 | Recurrent AIS as defined by proportion of participants who experience a recurrent AIS by Day 90 as assessed by a new, persistent neurological deficit attributable to cerebrovascular ischemia. Imaging findings, if available, should support the diagnosis. |
Countries
Belgium, Canada, France, Georgia, Hungary, Poland, Romania, Spain, United Kingdom, United States
Contacts
CONTACTShanique Smythe - Peterkin
PRINCIPAL_INVESTIGATORJay Volpi, M.D.
The Methodist Hospital Research Institute
PRINCIPAL_INVESTIGATORRachel Laursen, M.D.
Oregon Health & Science University (OHSU)
Outcome results
None listed