A study to learn if DM199 drug is safe and whether it works better than placebo for treating acute ischemic stroke

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Diamedica Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

4 Mar 2026 → ongoing

Decision date (initial)

2025-11-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DiaMedica Therapeutics Inc.

External identifiers

EU CT number

2024-513911-28-00

ClinicalTrials.gov

NCT05065216

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Therapy

The objective of this study is to evaluate the safety and efficacy of DM199 (rinvecalinase alfa) in participants with moderate stroke severity, who present within 24 hours of Acute Ischemic Stroke (AIS) onset/last known normal due to small and medium vessel occlusions. This study focuses on participants who have 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.

Conditions and MedDRA coding

Acute Ischemic Stroke

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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 infusion with investigational product 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 known normal/AIS stroke 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. Hemorrhagic transformation is defined as any of the following: ▪ PH1 or PH2 type hemorrhage based on Heidelberg Classification ▪ Hemorrhage resulting in neurologic deterioration Note: HI1 and HI2 type hemorrhages based on Heidelberg classification are not exclusionary.
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 20

1. At screening, or with repeat imaging (see Inclusion 4 and 6), participant has imaging confirmed hemorrhagic 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. Diagnostic angiogram without proceeding to MT is not exclusionary
5. Participant has suspected or confirmed extracranial arterial dissection.
6. Participant has imaging findings and 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 2 consecutive recorded measurements of SBP < 100 mm Hg or MAP <65 mm Hg; MAP = DBP + [1/3 (SBP – DBP)] after stroke symptom onset and within 6 hours 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 reported dose by the participant or their representative: • was taken less than 24 hours prior to the start of IV IP infusion for participants with normal or mild kidney disease (CKD 1-3a [eGFR ≥ 45 mL/min/1.73 m²]), or • was taken less than 48 hours prior to the start of IV IP infusion for participants with significant kidney disease (CKD 3b or higher [eGFR < 45 mL/min/1.73 m²])
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 (example treatment of an uncomplicated urinary tract infection or sinus infections with oral antibiotics would not be an exclusion).
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 who do not 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) 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 investigational product 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 (such as hemodialysis) which in the opinion of the Investigator will make participation medically unsafe or interfere with the study results.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. 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.
2. Incidence, severity, and causality of adverse events (AEs) and serious adverse events (SAEs).
3. Incidence, severity, and causality of adverse events of special interest (AESI).
4. Tolerability (incidence and severity of injection site adverse reactions).
5. Change from Baseline in physical examination (PE) at Day 21 and Day 90.
6. Change from Baseline in vital sign measurements (resting heart rate (HR), systolic/diastolic blood pressure (BP), respiratory rate (RR), and body temperature (BT)) at Days 1, 4, 21, and 90.
7. Change from Baseline in hematology and chemistry parameters at Day 4, Day 21, and Day 90.
8. Change from baseline in 12-lead Electrocardiogram (ECG) at Day 1 and Day 90 as determined by the Investigator.

Secondary endpoints 6

1. Assessment of effect on disability across the full spectrum of AIS by examining the distribution of mRS (shift) scores (scale range = 0 to 6) at Day 90.
2. Proportion of participants achieving independent function (able to look after their own affairs without assistance) with or without minor disability at Day 90 assessed as mRS 0-2 (dichotomized). mRS scores of 0, 1, or 2 represent responders, scale range of 0–6.
3. Mortality rate as defined by event rate (%) for mortality over 90 days.
4. Proportion of participants achieving an excellent neurological outcome defined by NIHSS = 0-1 (dichotomized) (NIHSS scores of 0 or 1, scale range 0 to 42) at Day 90.
5. Proportion of participants achieving an excellent functional independence in activities of daily living defined by Barthel Index score (dichotomized) greater than or equal to 95 (scale range 0 to 100) at Day 90.
6. Recurrent AIS as defined by proportion of participants who experience a recurrent AIS by Day 90 as assessed by a new, persistent neurological deficit attributable to cerebrovascular ischemia. Imaging findings, if available, should support the diagnosis.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Diamedica Therapeutics Inc.

Sponsor organisation

Diamedica Therapeutics Inc.

Address

301 Carlson Parkway Suite 210

City

Hopkins

Postcode

55305-5357

Country

United States

Scientific contact point

Organisation

Diamedica Therapeutics Inc.

Contact name

Swetha Kalidindi

Public contact point

Organisation

Diamedica Therapeutics Inc.

Contact name

CEO - Rick Pauls

Third parties 6

Locations

6 EU/EEA countries · 34 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 78 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications