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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Recombinant human tissue kallikrein
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is >/= 18 years of age Subject has been diagnosed with acute ischemic stroke with onset ≤ 24 hours from enrollment. Subject has NIH stroke score (NIHSS) ≥ 6 and ≤ 25. Subject or legally authorized representative is willing and able to sign written informed consent. Exclusion Criteria: 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. Subject has a history of significant allergic diathesis such as urticaria, angioedema or anaphylaxis. 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. Subject has a history of clinically significant acute bacterial, viral, or fungal systemic infections in the last four weeks prior to enrollment. Subject has clinical or laboratory evidence of an active infection at the time of enrollment. Subject has known alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency). Subject has a known diagnosis of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (Anti-HCV) at screening. Subject is pregnant or nursing. 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. 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. Subject does not have sufficient venous access for infusion of study treatment or blood sampling. In the opinion of the Investigator, subject is unlikely to be followed for the duration of t the study. Subject is unable or unwilling to comply with protocol requirements, including assessments, tests, and follow-up visits. Subject has any other medical condition which in the opinion of the Investigator will make participation medically unsafe or interfere with the study results. Pre-stroke Modified Rankin Scale ≥4

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |