Evaluation to Assess Safety and Tolerability of DM199 in Subjects With Acute Ischemic Stroke (ReMEDy1)

A Randomized, Double-blind, Placebo-controlled Phase II Multi-Center Evaluation to Assess the Safety and Tolerability of DM199 Administered Intravenously and Subcutaneously in Subjects With Acute Ischemic Stroke

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.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Recombinant human tissue kallikrein; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
  • Ballarat, Australia
    • Ballarat Health Services
  • Box Hill, Australia
    • Box Hill Hospital
  • New South Wales
    • Lismore, New South Wales, Australia
      • Lismore Base Hospital
    • Liverpool, New South Wales, Australia
      • Liverpool Hospital
    • New Lambton Heights, New South Wales, Australia
      • John Hunter Hospital
  • Queensland
    • Herston, Queensland, Australia
      • Royal Brisbane and Women's Hospital
    • Woolloongabba, Queensland, Australia
      • Princess Alexandria Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
    • St Albans, Victoria, Australia
      • Sunshine Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia
      • Fiona Stanley Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Recombinant human tissue kallikrein; Recombinant human tissue kallikrein; Other Names: DM199
Placebo Comparator: Placebo; A single IV infusion of 1 microgram/kg followed by 8 subcutaneous injections of 3 microgram/kg occurring every 72 hours.	Other: Placebo; Placebo Comparator: Phosphate buffered saline

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: DiaMedica Therapeutics Inc
• Investigators: Principal Investigator: Bruce Campbell, Melbourne Health

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2018
• Primary Completion (Actual): January 23, 2020
• Study Completion (Actual): January 23, 2020

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 20, 2017
• First Posted (Actual): September 25, 2017

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 17, 2022
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Coagulants; Reproductive Control Agents; Fertility Agents; Fertility Agents, Male; Kallikreins
• Other Study ID Numbers: DM199-2017-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No