Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Recombinant human tissue kallikrein · 3 trials · 4 indications
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. The mRS (Modified Rankin Scale) is a single-item, clinician-reported measure of functional disability in participants with AIS. Scores range in grade from 0 (no symptoms at all) to 6 (participant death).
Assessed by total number and severity of all treatment-related adverse events.
Assessment of safety of intravenous dosing
| Arm | Type | Description |
|---|---|---|
| DM199 | EXPERIMENTAL | 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. |
| Placebo for DM199 Solution for Injection | PLACEBO_COMPARATOR | 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. |
| Recombinant human tissue kallikrein | EXPERIMENTAL | A single IV infusion of 1 microgram/kg followed by 8 subcutaneous injections of 3 microgram/kg occurring every 72 hours. |
| Placebo | PLACEBO_COMPARATOR | A single IV infusion of 1 microgram/kg followed by 8 subcutaneous injections of 3 microgram/kg occurring every 72 hours. |
| Low dose (Part A) | EXPERIMENTAL | Recombinant human tissue kallikrein |
| Medium low dose (Part A) | EXPERIMENTAL | Recombinant human tissue kallikrein |
| Medium high dose (Part A) | EXPERIMENTAL | Recombinant human tissue kallikrein |
| High dose (Part A) | EXPERIMENTAL | Recombinant human tissue kallikrein |
| Subcutaneous (Part B) | EXPERIMENTAL | Recombinant human tissue kallikrein |
| IV (Part B) | EXPERIMENTAL | Recombinant human tissue kallikrein |
| Name | Type | Description |
|---|---|---|
| Recombinant human tissue kallikrein | DRUG | 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 |
| Placebo for DM199 Solution for Injection | OTHER | 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 | OTHER | Placebo Comparator: Phosphate buffered saline |
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...