Treatment of Acute Ischemic Stroke (ReMEDy2 Trial)

Sponsor

DiaMedica Therapeutics Inc (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT05065216

Collaborator

(none)

364

Enrollment

Locations

Arms

35.3

Anticipated Duration (Months)

24.3

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated 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)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 :

Sep 24, 2021

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

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 Names: 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 Names: DM199

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 Names:

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 Names:

DM199

Outcome Measures

Primary Outcome Measures

Modified rankin scores (mRs) of 0 or 1 represent responders [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)
Assessment of patients who experience recurrent stroke [Day 90]
Proportion of patients who experience a recurrent stroke by Day 90

Secondary Outcome Measures

Proportion of patients receiving excellent neurological outcome [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
Proportion of patients achieving an excellent functional independence in activities [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
Assessment of effect on disability across the full spectrum of strokes by examining the distribution of Modified Rankin Scores (mRS) [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
Mortality rate [Over 90 days]
As defined by event rate (%) for mortality

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient is ≥18 years of age.
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.

Patient has NIHSS ≥5 and ≤20.
Pre-morbid mRS score of 0-1 (mRS score prior to stroke).
Patient and/or legally authorized representative is able to participate in the informed consent process.
Patient's ability to comply with the study protocol, in the Investigator's judgment.

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington Regional Medical Center	Fayetteville	Arkansas	United States	72703
2	Glendale Adventist Medical Center d/b/a Adventist Health Glendale	Glendale	California	United States	91206-4152
3	St. Mary's Hospital and Regional Medical Center - St. Mary's Neurology Clinic	Grand Junction	Colorado	United States	81501-6132
4	Intercoastal Medical Group, Inc.	Sarasota	Florida	United States	34232
5	Tampa General Hospital (TGH) - The Stroke Center	Tampa	Florida	United States	33606-3603
6	NorthShore University HealthSystem Research Institute	Evanston	Illinois	United States	60201
7	Parkview Research Center	Fort Wayne	Indiana	United States	46845
8	Community Hospital - MacArthur	Munster	Indiana	United States	46321-2901
9	McLaren Macomb Hospital	Flint	Michigan	United States	48532-3638
10	The University of New Mexico - School of Medicine	Albuquerque	New Mexico	United States	87131
11	Mercy Hospital of Buffalo	Buffalo	New York	United States	14220
12	Guilford Neurologic Associates, Inc.	Greensboro	North Carolina	United States	27405
13	Ascension St. John	Tulsa	Oklahoma	United States	74104
14	The Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	Marshall University Medical Center - Cabell Huntington Hospital	Huntington	West Virginia	United States	25701