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Treatment of Acute Ischemic Stroke (ReMEDy2 Trial) (ReMEDy2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05065216
Recruitment Status : Active, not recruiting
First Posted : October 4, 2021
Last Update Posted : July 28, 2022
Sponsor:
Information provided by (Responsible Party):
DiaMedica Therapeutics Inc

Brief Summary:
This is a Phase 2/3 study to evaluate the safety, tolerability, and efficacy of DM199 in treating acute ischemic stroke patients presenting with AIS and for whom tPA and a catheter-based procedure, MT, are not medically appropriate or available due to constraints of clot location, comorbidity risks, and/or time from onset of stroke (LVO is excluded from this study). The double-blinded study will be randomized, placebo controlled at approximately 75 centers in the U.S.

Condition or disease Intervention/treatment Phase
Acute Stroke Ischemic Stroke Stroke Drug: Recombinant human tissue kallikrein Phase 2 Phase 3

Detailed Description:

This is a randomized, double-blind, placebo-controlled Phase 2/3 seamless adaptive, multi-center study to evaluate the efficacy, safety and tolerability of DM199. Patients presenting with acute ischemic stroke will be randomized in 1:1 to placebo or DM199 administered by a single intravenous (IV) dose 50ml over 40 minutes (within 24 hours of stroke onset) followed by a subcutaneous (SC) dose within 12 hours and then 2 times a week till Day 22. The duration of each individual's participation in the study will be 90 days from the time of consent 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 364 participants
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)
Masking: Double (Participant, Investigator)
Masking Description: To minimize bias, the patient 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.
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : September 24, 2021
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ischemic Stroke

Arm Intervention/treatment
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 till Day 22.
Drug: Recombinant human tissue kallikrein
Treatment is completed by Day 22 and the duration of each individual's participation in the study will be 90 days from the time of consent to completion of all study activities.
Other Name: DM199

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 till Day 22.
Drug: Recombinant human tissue kallikrein
Treatment is completed by Day 22 and the duration of each individual's participation in the study will be 90 days from the time of consent to completion of all study activities.
Other Name: DM199




Primary Outcome Measures :
  1. Modified rankin scores (mRs) of 0 or 1 represent responders [ Time Frame: Days 1,21 and 90 ]
    Stroke recovery as assessed by the proportion of patients with excellent functional outcomes at Day 90 (mRS of 0 or 1 represent responders) as assessed via the mRS score 0 - 6 (0 =no symptoms, 6 = death)

  2. Assessment of patients who experience recurrent stroke [ Time Frame: Day 90 ]
    Proportion of patients who experience a recurrent stroke by Day 90


Secondary Outcome Measures :
  1. Proportion of patients receiving excellent neurological outcome [ Time Frame: Day 90 ]
    Proportion of patients achieving an excellent neurological outcome defined by National Institutes of Health Stroke Scale (NIHSS) = 0-1 (scale range 0 No Stroke to 42 severe stroke) (dichotomized) at Day 90

  2. Proportion of patients achieving an excellent functional independence in activities [ Time Frame: Day 90 ]
    Proportion of patients achieving an excellent functional independence in activities of daily living defined by Barthel Index (BI) score greater than or equal to 95 (scale range 0 = Dependent on care to 100 = Normal) (dichotomized) at Day 90

  3. Assessment of effect on disability across the full spectrum of strokes by examining the distribution of Modified Rankin Scores (mRS) [ Time Frame: Day 90 ]
    Assessment of effect on disability across the full spectrum of strokes by examining the distribution of mRS scores (scale range = 0 = no symptoms to 6 = death) at Day 90 evaluated by shift analysis

  4. Mortality rate [ Time Frame: Over 90 days ]
    As defined by event rate (%) for mortality



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient is ≥18 years of age.
  2. Patient has been diagnosed with AIS within the last 24 hours.

    • Patient is not a candidate for tPA clinically or outside time window.
    • Patient is not a candidate for MT.
  3. Patient has NIHSS ≥5 and ≤20.
  4. Pre-morbid mRS score of 0-1 (mRS score prior to stroke).
  5. Patient and/or legally authorized representative is able to participate in the informed consent process.
  6. Patient's ability to comply with the study protocol, in the Investigator's judgment.

Exclusion Criteria:

  1. Patient has received or will receive tPA for the current AIS.
  2. Patient with imaging findings consistent with LVO.
  3. Patient has received MT or is scheduled to have a MT
  4. Patient has had a previous stroke.
  5. Patient has a hemorrhagic stroke

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05065216


Locations
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United States, Arkansas
Washington Regional Medical Center
Fayetteville, Arkansas, United States, 72703
United States, California
Glendale Adventist Medical Center d/b/a Adventist Health Glendale
Glendale, California, United States, 91206-4152
United States, Colorado
St. Mary's Hospital and Regional Medical Center - St. Mary's Neurology Clinic
Grand Junction, Colorado, United States, 81501-6132
United States, Florida
Intercoastal Medical Group, Inc.
Sarasota, Florida, United States, 34232
Tampa General Hospital (TGH) - The Stroke Center
Tampa, Florida, United States, 33606-3603
United States, Illinois
NorthShore University HealthSystem Research Institute
Evanston, Illinois, United States, 60201
United States, Indiana
Parkview Research Center
Fort Wayne, Indiana, United States, 46845
Community Hospital - MacArthur
Munster, Indiana, United States, 46321-2901
United States, Michigan
McLaren Macomb Hospital
Flint, Michigan, United States, 48532-3638
United States, New Mexico
The University of New Mexico - School of Medicine
Albuquerque, New Mexico, United States, 87131
United States, New York
Mercy Hospital of Buffalo
Buffalo, New York, United States, 14220
United States, North Carolina
Guilford Neurologic Associates, Inc.
Greensboro, North Carolina, United States, 27405
United States, Oklahoma
Ascension St. John
Tulsa, Oklahoma, United States, 74104
United States, Pennsylvania
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, West Virginia
Marshall University Medical Center - Cabell Huntington Hospital
Huntington, West Virginia, United States, 25701
Sponsors and Collaborators
DiaMedica Therapeutics Inc
Investigators
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Principal Investigator: Scott Kasner, MD Uni Penn
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Responsible Party: DiaMedica Therapeutics Inc
ClinicalTrials.gov Identifier: NCT05065216    
Other Study ID Numbers: DM199-2021-001
First Posted: October 4, 2021    Key Record Dates
Last Update Posted: July 28, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by DiaMedica Therapeutics Inc:
acute
ischemic
stroke
AIS
tPA
LVO
MT
KLK1
Kallikreins
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Infarction
Necrosis
Kallikreins
Coagulants
Fertility Agents, Male
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs