Treatment of Acute Ischemic Stroke (ReMEDy2 Trial)

NCT ID: NCT05065216

Last Updated: 2025-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

728 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-07

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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Acute Stroke Ischemic Stroke Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
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.

Study Groups

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DM199

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.

Group Type EXPERIMENTAL

Recombinant human tissue kallikrein

Intervention Type DRUG

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

Placebo 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.

Group Type PLACEBO_COMPARATOR

Placebo for DM199 Solution for Injection

Intervention Type OTHER

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.

Interventions

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Recombinant human tissue kallikrein

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

Intervention Type DRUG

Placebo 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.

Intervention Type OTHER

Other Intervention Names

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DM199

Eligibility Criteria

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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

Exclusion Criteria

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
7. Participant and/or legally authorized representative is able to provide informed consent.
8. Participant is willing and able to comply with the study protocol, in the Investigator's judgment.


1. At screening, or with repeat imaging (see Inclusion 4 and 6), participant has imaging confirmed hemorrhage stroke.
2. Participant has image findings with symptomatic large vessel occlusion at one or more of the following locations: Intracranial carotid I/T/L or M1 segment MCA, vertebral or basilar artery (BA).
3. Participant has large core of established infarction defined as ASPECTS 0-5.
4. Participant has or will receive MT for their current AIS.
5. Participant has suspected or confirmed extracranial arterial dissection.
6. Participant has imaging findings and/or symptoms consistent with a brain stem or cerebellar stroke. Posterior cerebral artery strokes without any associated brain stem or cerebellar involvement are allowable.
7. Participant has any recorded SBP \<100 mmHg or MAP \<65 mmHg; 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. 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. Participant has a diagnosis or suspected diagnosis of hereditary angioedema (HAE) or is taking or prescribed medications commonly used as prophylaxis/treatment of HAE, such as C1-esterase inhibitors (Cinryze, Berinert, Ruconest, Haegarda), Danazol, kallikrein inhibitors (Ecallantide, Berotralstat, Lanadelumab), Bradykinin B2 Receptor Antagonists (Icatibant), or other medication designed to influence the kallikrein-kinin system.
12. Life expectancy estimated at ≤1 year prior to enrollment.
13. 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 (for example, the treatment of uncomplicated urinary tract infections or sinus infections with oral antibiotics would not be exclusionary).
14. Participant has known alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency).
15. Participant is pregnant or nursing. NOTE: Participants who agree to stop nursing may be considered for inclusion at the discretion of the Investigator.
16. 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, bilateral salpingectomy, etc.) 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.
17. 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.
18. Participant does not have sufficient venous access for infusion of study treatment or blood sampling.
19. Participant is unable or unwilling to comply with protocol requirements, including assessments, tests, and follow-up visits.
20. Participant has any other medical condition which in the opinion of the Investigator will make participation medically unsafe or interfere with the study results.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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DiaMedica Therapeutics Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jay Volpi, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Methodist Hospital Research Institute

Rachel Laursen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Oregon Health & Science University (OHSU)

Locations

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Gulf Health Hospitals d/b/a Thomas Hospital

Fairhope, Alabama, United States

Site Status RECRUITING

USC Arcadia Hospital

Arcadia, California, United States

Site Status RECRUITING

Glendale Adventist Medical Center d/b/a Adventist Health Glendale

Glendale, California, United States

Site Status RECRUITING

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Site Status RECRUITING

The Lundquist Institute at Harbor UCLA Medical Center

Torrance, California, United States

Site Status RECRUITING

Memorialcare Long Beach Medical Center

Torrance, California, United States

Site Status RECRUITING

HCA Florida - JFK Medical Center

Atlantis, Florida, United States

Site Status RECRUITING

University of Florida Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

Sarasota Memorial Hospital

Sarasota, Florida, United States

Site Status RECRUITING

Tampa General Hospital (TGH) - The Stroke Center

Tampa, Florida, United States

Site Status RECRUITING

OSF HealthCare Saint Francis Medical Center

Peoria, Illinois, United States

Site Status RECRUITING

Community Hospital - MacArthur

Munster, Indiana, United States

Site Status ACTIVE_NOT_RECRUITING

Ascension Via Christi Hospitals Wichita Inc.

Wichita, Kansas, United States

Site Status RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status RECRUITING

UMASS Chan Medical School

Worcester, Massachusetts, United States

Site Status RECRUITING

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan, United States

Site Status RECRUITING

Abbott Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status RECRUITING

The University of New Mexico - School of Medicine

Albuquerque, New Mexico, United States

Site Status RECRUITING

Northwell Health Physician Partners - Neurology at Lenox Hill

New York, New York, United States

Site Status RECRUITING

Summa Health Clinical Research Center

Akron, Ohio, United States

Site Status RECRUITING

The Clinical Neuroscience Institute

Dayton, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Mercy Health - St. Vincent Medical Center

Toledo, Ohio, United States

Site Status RECRUITING

The University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Ascension St. John

Tulsa, Oklahoma, United States

Site Status ACTIVE_NOT_RECRUITING

Oregon Health & Science University

Portland, Oregon, United States

Site Status RECRUITING

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Prisma Health-Greenville Memorial Hospital

Greenville, South Carolina, United States

Site Status RECRUITING

Erlanger Hospital

Chattanooga, Tennessee, United States

Site Status RECRUITING

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, United States

Site Status RECRUITING

Houston Methodist Neurological Institute

Houston, Texas, United States

Site Status RECRUITING

Memorial Hermann Hospital, Texas Medical Center

Houston, Texas, United States

Site Status RECRUITING

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

Health Sciences North

Hamilton, Ontario, Canada

Site Status RECRUITING

Hamilton Health Sciences - Hamilton General Hospital

Hamilton, Ontario, Canada

Site Status RECRUITING

West Georgia Medical Center LTD

Kutaisi, Georgia, Georgia

Site Status RECRUITING

Israel-Georgia Medical Research Clinic-Healthycore LTD

Tbilisi, Georgia, Georgia

Site Status RECRUITING

New Hospitals LTD

Tbilisi, Georgia, Georgia

Site Status RECRUITING

Pineo Medical Ecosystem LTD

Tbilisi, Georgia, Georgia

Site Status RECRUITING

JSC K. Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, Georgia, Georgia

Site Status RECRUITING

Royal Stoke University Hospital

Stoke-on-Trent, United Kingdom, United Kingdom

Site Status RECRUITING

Countries

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United States Canada Georgia United Kingdom

Central Contacts

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Kayla Slupek

Role: CONTACT

(717)304-7442

Adrienne Ford

Role: CONTACT

(717)658-6652

Facility Contacts

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Richard Friedman, M.D.

Role: primary

251-435-2400

Rosalina Mayorga

Role: primary

626-898-8322

Lance J Lee, MD

Role: primary

+1 818-243-1501

Shayandokht Taleb, M.D.

Role: primary

(323) 783-7387

Ileana Grunberg

Role: primary

(888) 888-8888

Aljohn Cabuang

Role: primary

(424) 571-7755

Nima Ramezan-Arab, MD

Role: primary

(562) 430-4513

Mailer Fonseca

Role: primary

(561) 358-9998

Yasmeen Shabbir

Role: primary

9042449856

Mauricio Concha, M.D.

Role: primary

(941) 330-1864

David Rose, MD

Role: primary

Arun Talkad, M.D.

Role: primary

(309) 624-7552

Toni Sadler

Role: primary

316-268-5932

Jessica Henry

Role: primary

(504) 842-8627

Nimmy Francis

Role: primary

508-856-4677

Muhammad Farooq, MD

Role: primary

(616) 916-6151

Ganesh Asaithambi, M.D.

Role: primary

612-863-0376

Maryam Hosseini, MD

Role: primary

Salman Azhar, MD

Role: primary

Jeremy Kick

Role: primary

(330) 375-3244

Osama Zaidat, MD

Role: primary

(419) 251-3232

Jorge Ortiz Garcia, M.D.

Role: primary

(405) 271-4113

Rachel Laursen, M.D.

Role: primary

(503) 494-7191

Nichole Gallatti

Role: primary

+1 215-349-8651

Reilly Leonard

Role: primary

8646089207

Mounzer Yassin-Kassab, MD

Role: primary

Thomas Devlin, M.D.

Role: primary

(423) 648-0304

Rajan Gadhia, M.D

Role: primary

(713) 363-9065

David McCane

Role: backup

(713) 441-5801

Andrew Barretto, M.D.

Role: primary

(713) 500-7066

Prasen Marella

Role: backup

(713) 500-5719

Ashfaq Shuaib

Role: primary

(780) 248-1927

Danna Puchailo

Role: backup

(780) 248-1660

Carson Ma

Role: primary

6048754111

Mythili Velma

Role: primary

705-523-7100 ext. 1932

Shuhira Himed

Role: primary

(905) 521-2100

Tamar Janelidze, M.D.

Role: primary

+995 598 721 985

Zurabi Akhalaia, M.D.

Role: primary

+ 995 599 050 169

Temur Margania, M.D

Role: primary

+ 995 571170194

Nikoloz Tsiskaridze, M.D.

Role: primary

+995 599 804 090

Giorgi Egutidze, M.D.

Role: primary

+995 592 773 938

Joanne Hiden

Role: primary

+44 1782-672730

Other Identifiers

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DM199-2021-001

Identifier Type: -

Identifier Source: org_study_id

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