Evaluation to Assess Safety and Tolerability of DM199 in Subjects With Acute Ischemic Stroke

Phase 2

Completed

• Conditions: Acute Ischemic Stroke
• Interventions: Other: Placebo; Drug: Recombinant human tissue kallikrein

• Registration Number: NCT03290560
• Lead Sponsor: DiaMedica Therapeutics Inc

Brief Summary

This is a Phase II study to assess the safety and tolerability of DM199 in acute ischemic stroke patients. The study will be randomized, placebo controlled at multiple centers.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-09-18
• Study First Submitted QC: 2017-09-20
• Study First Posted: 2017-09-25
• Study Start: 2018-01-19
• Primary Completion: 2020-01-23
• Study Completion: 2020-01-23
• Status Verified: 2020-02
• Last Update Submitted: 2022-03-17
• Last Update Posted: 2022-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

1. Subject is >/= 18 years of age
2. Subject has been diagnosed with acute ischemic stroke with onset ≤ 24 hours from enrollment.
3. Subject has NIH stroke score (NIHSS) ≥ 6 and ≤ 25.
4. Subject or legally authorized representative is willing and able to sign written informed consent.

Exclusion Criteria

1. Subject is currently prescribed angiotensin-converting-enzyme inhibitors (ACEi) and is unable or unwilling to convert to another antihypertensive pharmacological treatment during the active treatment period (+5 days) of the study.
2. Subject has a history of significant allergic diathesis such as urticaria, angioedema or anaphylaxis.
3. Subjects with current malignancy or active malignancy ≤ 3 years prior to enrollment except basal cell or squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy and at least six months have elapsed since the procedure.
4. Subject has a history of clinically significant acute bacterial, viral, or fungal systemic infections in the last four weeks prior to enrollment.
5. Subject has clinical or laboratory evidence of an active infection at the time of enrollment.
6. Subject has known alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency).
7. Subject has a known diagnosis of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (Anti-HCV) at screening.
8. Subject is pregnant or nursing.
9. Subject is male or female of childbearing potential, is participating in heterosexual sexual activity that could lead to pregnancy, and is unable or unwilling to practice medically effective contraception during the study.
10. Subject is participating in any other investigational device or other drug study ≤ 4 weeks or 5 half-lives of the investigational product, whichever is longer.
11. Subject does not have sufficient venous access for infusion of study treatment or blood sampling.
12. In the opinion of the Investigator, subject is unlikely to be followed for the duration of t the study.
13. Subject is unable or unwilling to comply with protocol requirements, including assessments, tests, and follow-up visits.
14. Subject has any other medical condition which in the opinion of the Investigator will make participation medically unsafe or interfere with the study results.
15. Pre-stroke Modified Rankin Scale ≥4

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	A single IV infusion of 1 microgram/kg followed by 8 subcutaneous injections of 3 microgram/kg occurring every 72 hours.
Recombinant human tissue kallikrein	Recombinant human tissue kallikrein	A single IV infusion of 1 microgram/kg followed by 8 subcutaneous injections of 3 microgram/kg occurring every 72 hours.

Primary Outcome Measures

Name	Time	Method
Number of participants with treatment-related adverse events as assessed by CTCAE v4.3	90 Days	Assessed by total number and severity of all treatment-related adverse events.

Secondary Outcome Measures

Name	Time	Method
Changes from baseline to Day 90 of Modified Rankin Scale.	90 Days	Assessed by a reduction in points from baseline.
Changes from baseline to Day 90 of NIH Stroke Scale.	90 Days	Assessed by a reduction in points from baseline.
Changes from baseline to Day 90 of Barthel Index.	90 Days	Assessed by an increase in points from baseline.

Trial Locations

Locations (12)

Lismore Base Hospital; 🇦🇺 Lismore, New South Wales, Australia

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

John Hunter Hospital; 🇦🇺 New Lambton Heights, New South Wales, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Herston, Queensland, Australia

Princess Alexandria Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Alfred Health; 🇦🇺 Melbourne, Victoria, Australia

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

Sunshine Hospital; 🇦🇺 St Albans, Victoria, Australia

Fiona Stanley Hospital; 🇦🇺 Murdoch, Western Australia, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Ballarat Health Services; 🇦🇺 Ballarat, Australia

Box Hill Hospital; 🇦🇺 Box Hill, Australia