Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Recombinant human tissue kallikrein, recombinant human tissue kallikrein-1, tissue kallikrein-1
DM199 · 6 trials · 10 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).
Incidence, severity, and causality of adverse events
eGFR
UACR change from baseline
Maximum plasma concentration of DM199
Assessed by total number and severity of all treatment-related adverse events.
urine KLK1 will be measured pre and post study drug administration.
Assessment of safety of intravenous dosing
Number of participants with adverse events in the single and multiple ascending dose studies.
Determine the plasma pharmacokinetic profile of DM199 after administration of single and multiple doses of DM199 in healthy subjects and type 2 diabetes mellitus patients. Measure plasma DM199 levels in individual participants.
| 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. |
| 2.0 µg/kg, multiple dose | EXPERIMENTAL | n=45 with 15 Participants from cohort 1, 15 from cohort 2, and 15 from cohort 3 |
| 5.0 µg/kg, multiple dose | EXPERIMENTAL | n=45 with 15 Participants from cohort 1, 15 from cohort 2 and 15 from cohort 3 |
| 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. |
| 3.0 µg/kg SC, single dose | EXPERIMENTAL | n=8, study group of T1D or T2D with stage 3 CKD. separate n=8 of study group with T1D or T2D with CKD stage 4). |
| 5.0 µg/kg SC, single dose | EXPERIMENTAL | n=8, study group of T1D or T2D with stage 3 CKD. |
| 8.0 µg/kg SC, single dose | EXPERIMENTAL | n=8, study group of T1D or T2D with stage 3 CKD. |
| 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 |
| Part A - SAD in healthy subjects | EXPERIMENTAL | A randomized, double-blinded, placebo-controlled, single ascending dose (SAD) study in healthy male and/or female subjects. Subjects will receive DM199 subcutaneously (sc). |
| Part B - SAD in type 2 diabetic patients | EXPERIMENTAL | A randomized, partially double-blinded, placebo-controlled, sequential SAD study in male and/or female type 2 diabetes mellitus patients. Subjects will receive DM199 subcutaneously (sc). |
| Part C - MAD in healthy subjects | EXPERIMENTAL | A randomized, double-blinded, placebo-controlled, 14-day multiple ascending dose (MAD) study in healthy male and/or female subjects each. Subjects will receive sequential doses of DM199 sc for 14 days. |
| Part D - POC in type 2 diabetes patients | EXPERIMENTAL | A randomized, double-blinded, placebo-controlled, 28-day multiple-dose proof of concept (POC) study in male and/or female type 2 diabetes mellitus patients. Subjects will receive doses of DM199 sc for 28 days. |
| Part A - Healthy subjects SAD placebo | PLACEBO_COMPARATOR | A randomized, double-blinded, placebo-controlled, single ascending dose (SAD) study in healthy male and/or female subjects. Subjects will receive placebo subcutaneously (sc). |
| Part B - Type 2 diabetic patients SAD placebo | PLACEBO_COMPARATOR | A randomized, partially double-blinded, placebo-controlled, sequential SAD study in male and/or female type 2 diabetes mellitus patients. Subjects will receive placebo subcutaneously (sc). |
| Part C - Healthy subjects MAD placebo | PLACEBO_COMPARATOR | A randomized, double-blinded, placebo-controlled, 14-day multiple ascending dose (MAD) study in healthy male and/or female subjects each. Subjects will receive placebo sc for 14 days. |
| Part D - Type 2 diabetic patients POC placebo | PLACEBO_COMPARATOR | A randomized, double-blinded, placebo-controlled, 28-day multiple-dose proof of concept (POC) study in male and/or female type 2 diabetes mellitus patients. Subjects will receive placebo sc for 28 days. |
| 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. |
| DM199 | DRUG | A pharmaceutical formulation comprised of recombinant human tissue kallikrein-1 (rhKLK-1) that is being developed as an injectable protein drug |
| 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...
DM199 is an investigational small molecule developed by DiaMedica Therapeutics Inc. (ticker DMAC). It is being studied in clinical trials for acute ischemic stroke and chronic kidney disease, including patients with type 2 diabetes. DM199 is also known as recombinant human tissue kallikrein and is not yet approved for any indication.
DM199 is being evaluated as a treatment for acute ischemic stroke. The ongoing ReMEDy2 trial (NCT05065216) is a Phase 2 study in patients with acute ischemic stroke, and an earlier Phase 2 study (NCT03290560) also assessed DM199 in this condition. It remains investigational for this use.
DM199 targets KLK1, a protein also known as tissue kallikrein. As a recombinant form of human tissue kallikrein, DM199 is designed to act on the KLK1 pathway. This mechanism is being explored in clinical studies for acute ischemic stroke and chronic kidney disease.
DM199 is being developed by DiaMedica Therapeutics Inc., which trades under the ticker DMAC. The company is responsible for the clinical development program, including the ongoing Phase 2 ReMEDy2 trial in acute ischemic stroke and completed studies in chronic kidney disease.
DM199 is in Phase 2 clinical development. The active ReMEDy2 trial (NCT05065216) is a Phase 2 study in acute ischemic stroke, and completed Phase 2 studies include NCT04123613 in chronic kidney disease and NCT03290560 in acute ischemic stroke. DM199 is investigational and has not been approved by the FDA.
DM199 has been studied in several clinical trials. The ongoing Phase 2 ReMEDy2 trial (NCT05065216) is recruiting 728 patients with acute ischemic stroke across multiple countries. Completed trials include Phase 2 studies NCT04123613 in chronic kidney disease and NCT03290560 in acute ischemic stroke, plus Phase 1 NCT03795389 in diabetes and chronic kidney disease.
Yes, DM199 is also known as recombinant human tissue kallikrein. It is a recombinant form of the human KLK1 protein. This alternative name is used in scientific and regulatory contexts, but DM199 is the company's development code for the same investigational product.