Treatment of Acute Ischemic Stroke (ReMEDy2 Trial)

Purpose

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

  • Acute Stroke
  • Ischemic Stroke
  • Stroke

Eligibility

Eligible Ages
Between 18 Years and 90 Years
Eligible Sex
All
Accepts 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 exclusion criteria including repeat brain imaging to rule out hemorrhagic transformation. 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. Exclusion Criteria: 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.

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
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)
Primary Purpose
Treatment
Masking
Double (Participant, 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.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Drug: 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
    Other names:
    • DM199
  • Other: 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.
Placebo Comparator
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.
  • Other: 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.

Recruiting Locations

Gulf Health Hospitals d/b/a Thomas Hospital
Fairhope, Alabama 36532
Contact:
Richard Friedman, M.D.
251-435-2400
rhonda.dickinson@infirmaryhealth.org

USC Arcadia Hospital
Arcadia, California 91007
Contact:
Rosalina Mayorga
626-898-8322
rosalina.mayorga@med.usc.edu

Glendale Adventist Medical Center d/b/a Adventist Health Glendale
Glendale, California 91206-4152
Contact:
Lance J Lee, MD
+1 818-243-1501
lancelee@charter.net

Kaiser Permanente Los Angeles Medical Center
Los Angeles, California 90027-5209
Contact:
Shayandokht Taleb, M.D.
(323) 783-7387
shayandokht.x.taleb@kp.org

Ronald Reagan UCLA Medical Center
Los Angeles, California 90095
Contact:
Ileana Grunberg
(888) 888-8888
igrunberg@mednet.ucla.edu

Stanford Health Care
Stanford, California 94305
Contact:
Nhi Nguyen
(650) 723-6469
nhiquero@stanford.edu

The Lundquist Institute at Harbor UCLA Medical Center
Torrance, California 90502
Contact:
Aljohn Cabuang
(424) 571-7755
aljohn.cabuang@lundquist.org

Memorialcare Long Beach Medical Center
Torrance, California 90806
Contact:
Nima Ramezan-Arab, MD
(562) 430-4513
nramezan@gmail.com

HCA Florida - JFK Medical Center
Atlantis, Florida 33462-1149
Contact:
Mailer Fonseca
(561) 358-9998
Mailer.Fonseca@hcahealthcare.com

Holy Cross Health
Fort Lauderdale, Florida 33308
Contact:
Ashley Jean-Joseph
954-542-8554
ashley.jean-joseph@holy-cross.com

University of Florida Jacksonville
Jacksonville, Florida 32209
Contact:
Yasmeen Shabbir
9042449856
Yasmeen.Shabbir@jax.ufl.edu

Sarasota Memorial Hospital
Sarasota, Florida 34239-2617
Contact:
Mauricio Concha, M.D.
(941) 330-1864
mconcha@intercoastalmedical.com

Tampa General Hospital (TGH) - The Stroke Center
Tampa, Florida 33606-3603
Contact:
David Rose, MD
drose1@health.usf.edu

OSF HealthCare Saint Francis Medical Center
Peoria, Illinois 61637
Contact:
Arun Talkad, M.D.
(309) 624-7552
arun.v.talkad@osfhealthcare.org

Ascension Via Christi Hospitals Wichita Inc.
Wichita, Kansas 67214
Contact:
Toni Sadler
316-268-5932
Toni.Sadler@ascension.org

Ochsner Clinic Foundation
New Orleans, Louisiana 70121
Contact:
Jessica Henry
(504) 842-8627
jehenry@ochsner.org

UMASS Chan Medical School
Worcester, Massachusetts 01655
Contact:
Nimmy Francis
508-856-4677
nimmy.francis@umassmemorial.org

Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan 49503
Contact:
Muhammad Farooq, MD
(616) 916-6151
farooqmu@trinity-health.org

Abbott Northwestern Hospital
Minneapolis, Minnesota 55407
Contact:
Ganesh Asaithambi, M.D.
612-863-0376
marie.meyer@allina.com

University Medical Center of Southern Nevada
Las Vegas, Nevada 89102
Contact:
Robert Panganiban
17023837336
robert.panganiban@umcsn.com

The University of New Mexico - School of Medicine
Albuquerque, New Mexico 87131
Contact:
Maryam Hosseini, MD
MHosseini@salud.unm.edu

Northwell Health Physician Partners - Neurology at Lenox Hill
New York, New York 10075
Contact:
Salman Azhar, MD
sazhar@lmcmc.com

Summa Health Clinical Research Center
Akron, Ohio 44304
Contact:
Jeremy Kick
(330) 375-3244
kickj@summahealth.org

Mercy Health - St. Vincent Medical Center
Toledo, Ohio 43608
Contact:
Osama Zaidat, MD
(419) 251-3232
oozaidat@mercy.com

The University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
Contact:
Jorge Ortiz Garcia, M.D.
(405) 271-4113
jorge-ortizgarcia@ouhsc.edu

Oregon Health & Science University
Portland, Oregon 97239
Contact:
Rachel Laursen, M.D.
(503) 494-7225
laursen@ohsu.edu

The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania 19104
Contact:
Nichole Gallatti
+1 215-349-8651
nichole.gallatti@pennmedicine.upenn.edu

Prisma Health-Greenville Memorial Hospital
Greenville, South Carolina 29605
Contact:
Reilly Leonard
8646089207
reilly.leonard@prismahealth.org

Erlanger Hospital
Chattanooga, Tennessee 37403
Contact:
Mounzer Yassin-Kassab, MD
Mounzer.Kassab@erlanger.org

Chattanooga Center for Neurologic Research
Chattanooga, Tennessee 37404-1163
Contact:
Thomas Devlin, M.D.
(423) 648-0304
devlinmdphd@gmail.com

Houston Methodist Neurological Institute
Houston, Texas 77030
Contact:
Rajan Gadhia, M.D
(713) 363-9065
rrgadhia@houstonmethodist.org

Memorial Hermann Hospital, Texas Medical Center
Houston, Texas 77030
Contact:
Andrew Barretto, M.D.
(713) 500-7066
prasen.r.marella@uth.tmc.edu

More Details

Status
Recruiting
Sponsor
DiaMedica Therapeutics Inc

Study Contact

Kayla Slupek
(717)304-7442
kslupek@diamedica.com

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.