Treatment of Acute Ischemic Stroke (ReMEDy2 Trial)

NCT05065216 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DM199-2021-001
• Study Type: interventional
• Target: 728
• Locations: 9 countries
• Sites: 66

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.

Conditions

Stroke; Acute Stroke; Ischemic Stroke

Keywords

acute; ischemic; stroke; AIS; tPA; LVO; MT; KLK1; Kallikreins

Outcome Measures

Primary Outcomes (1)

• Stroke Recovery

  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).

  Day 90

Secondary Outcomes (6)

• Effect on Disability

  Day 90

• Independent Function

  Day 90

• Mortality Rate

  Day 90

• Neurological Outcome

  Day 90

• Functional Independence

  Day 90

Study Arms (2)

DM199

EXPERIMENTAL

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.

Drug: Recombinant human tissue kallikrein

Placebo for DM199 Solution for Injection

PLACEBO COMPARATOR

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.

Other: Placebo for DM199 Solution for Injection

Interventions

Placebo for DM199 Solution for Injection 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.

Placebo for DM199 Solution for Injection

Recombinant human tissue kallikrein 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

Also known as: DM199

DM199

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is between 18 and 90 years of age inclusive.
• Participant weight is 40 kg to 166 kg inclusive.
• Participant to be randomized and treatment initiated within 24 hours of last known normal/AIS stroke onset.
• 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

You may not qualify if:

• Participant had a pre-morbid mRS score of 0 to 1 (mRS score prior to AIS) as stated by participant or participant's representative.
• 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 and/or legally authorized representative is able to provide informed consent.
• Participant is willing and able to comply with the study protocol, in the Investigator's judgment.
• 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).
• Participant has large core of established infarction defined as ASPECTS 0-5.
• Participant has or will receive MT for their current AIS.
• Participant has suspected or confirmed extracranial arterial dissection.
• 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.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• DiaMedica Therapeutics Inc: lead

Study Sites (66)

Gulf Health Hospitals d/b/a Thomas Hospital

Fairhope, Alabama, 36532, United States

RECRUITING

USC Arcadia Hospital

Arcadia, California, 91007, United States

RECRUITING

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

Glendale, California, 91206-4152, United States

RECRUITING

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027-5209, United States

RECRUITING

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

RECRUITING

Stanford Health Care

Stanford, California, 94305, United States

RECRUITING

The Lundquist Institute at Harbor UCLA Medical Center

Torrance, California, 90502, United States

RECRUITING

Memorialcare Long Beach Medical Center

Torrance, California, 90806, United States

RECRUITING

HCA Florida - JFK Medical Center

Atlantis, Florida, 33462-1149, United States

RECRUITING

Boca Raton Regional Hospital Marcus Neuroscience Institute

Boca Raton, Florida, 33486, United States

RECRUITING

Holy Cross Health

Fort Lauderdale, Florida, 33308, United States

RECRUITING

University of Florida Jacksonville

Jacksonville, Florida, 32209, United States

RECRUITING

Sarasota Memorial Hospital

Sarasota, Florida, 34239-2617, United States

RECRUITING

Tampa General Hospital (TGH) - The Stroke Center

Tampa, Florida, 33606-3603, United States

RECRUITING

OSF HealthCare Saint Francis Medical Center

Peoria, Illinois, 61637, United States

RECRUITING

Ascension Via Christi Hospitals Wichita Inc.

Wichita, Kansas, 67214, United States

RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

RECRUITING

UMASS Chan Medical School

Worcester, Massachusetts, 01655, United States

RECRUITING

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan, 49503, United States

RECRUITING

Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

RECRUITING

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

RECRUITING

The University of New Mexico - School of Medicine

Albuquerque, New Mexico, 87131, United States

RECRUITING

Northwell Health Physician Partners - Neurology at Lenox Hill

New York, New York, 10075, United States

RECRUITING

Summa Health Clinical Research Center

Akron, Ohio, 44304, United States

RECRUITING

The Clinical Neuroscience Institute

Dayton, Ohio, 45431, United States

ACTIVE NOT RECRUITING

Mercy Health - St. Vincent Medical Center

Toledo, Ohio, 43608, United States

RECRUITING

The University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Ascension St. John

Tulsa, Oklahoma, 74104, United States

ACTIVE NOT RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Prisma Health-Greenville Memorial Hospital

Greenville, South Carolina, 29605, United States

RECRUITING

Erlanger Hospital

Chattanooga, Tennessee, 37403, United States

RECRUITING

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, 37404-1163, United States

RECRUITING

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

RECRUITING

Memorial Hermann Hospital, Texas Medical Center

Houston, Texas, 77030, United States

RECRUITING

Imeldaziekenhuis (Imelda Hospital)

Bonheiden, Belgium, 015 50 50 11, Belgium

RECRUITING

UZ Gent

Ghent, Belgium, 9000, Belgium

RECRUITING

Jessa Ziekenhuis

Hasselt, Belgium, 3500, Belgium

RECRUITING

AZ Groeninge

Kortrijk, Belgium, 8500, Belgium

RECRUITING

Clinique St Pierre

Ottignies, Belgium, 1340, Belgium

RECRUITING

University of Alberta Hospital

Edmonton, Alberta, T6G 2G3 7802481660, Canada

RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, V5Z1M9, Canada

RECRUITING

Health Sciences North

Hamilton, Ontario, L8L2X2, Canada

RECRUITING

Hamilton Health Sciences - Hamilton General Hospital

Hamilton, Ontario, L8L8E7, Canada

RECRUITING

Sunnybrook Research Institute

North York, Ontario, M4N 3M5, Canada

RECRUITING

CHU Pontchaillou /Hopital Sud Service de Neurologie

Rennes, Brittany Region, 35033, France

RECRUITING

West Georgia Medical Center LTD

Kutaisi, Georgia, 4600, Georgia

RECRUITING

Israel-Georgia Medical Research Clinic-Healthycore LTD

Tbilisi, Georgia, 0112, Georgia

RECRUITING

New Hospitals LTD

Tbilisi, Georgia, 0114, Georgia

RECRUITING

Pineo Medical Ecosystem LTD

Tbilisi, Georgia, 0114, Georgia

RECRUITING

JSC K. Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, Georgia, 0159, Georgia

RECRUITING

Bajcsy-Zsilinszky Hospital

Budapest, Hungary, 1106, Hungary

RECRUITING

St. Damjan Greek Catholic Hospital

Kisvárda, Hungary, 4600, Hungary

RECRUITING

B.-A.-Z. County Central Hospital

Miskolc, Hungary, 3526, Hungary

RECRUITING

Petz Aladár County Teaching Hospital

Győr, Vasvári Pál U. 2-4, 9024, Hungary

RECRUITING

Fundeni Clinical Institute

Bucharest, Bucharest (Sector 2), 022328, Romania

RECRUITING

Elias Emergency University Hospital

Bucharest, Romania, 011461, Romania

RECRUITING

Instituto de Investigacion Biomedica de A Coruna (INIBIC)

A Coruña, Spain, 15006, Spain

RECRUITING

Hospital Universitario Germans Trias i Pujol

Badalona, Spain, 8916, Spain

RECRUITING

Hospital Universitari Vall d'Hebron-Institut de Recerca

Barcelona, Spain, 8035, Spain

RECRUITING

Hospital Clínico Universitario de Santiago

Santiago de Compostela, Spain, 15706, Spain

RECRUITING

Royal Devon and Exeter Hospital

Exeter, Devon, EX25DW, United Kingdom

RECRUITING

The Newcastle upon Tyne Hospitals NHS Foundation Trust - Royal Victoria Infirmary (RVI)

Newcastle upon Tyne, England, NE1 4LP, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, United Kingdom, CB2 0QQ, United Kingdom

RECRUITING

St George's Hospital

London, United Kingdom, SW17 0QT, United Kingdom

RECRUITING

Royal Stoke University Hospital

Stoke-on-Trent, United Kingdom, ST4 6QG, United Kingdom

RECRUITING

MeSH Terms

Conditions

Stroke; Ischemic Stroke; Ischemia

Interventions

DM199; Injections

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Jay Volpi, M.D.

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Rachel Laursen, M.D.

  Oregon Health & Science University (OHSU)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kayla Slupek

CONTACT

(717)304-7442; kslupek@diamedica.com

Adrienne Ford

CONTACT

(717)658-6652; aford@diamedica.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: October 4, 2021
• Study Start: November 7, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); HU (4); ES (4); BE (5); RO (2); US (35); CA (5); GB (5); GE (5)