Abstract: PO2526
REDUX: A Multicenter, Open-Label Study of DM199 (Recombinant Human Tissue Kallikrein-1) in Patients with Stage 2 or 3 CKD
Session Information
- Late-Breaking Clinical Trials Posters
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Alcorn, Harry W., DiaMedica Therapeutics, Minneapolis, Minnesota, United States
- Silva, Arnold L., Boise Kidney & Hypertension Institute, Meridan, Idaho, United States
- Yablon, Zachary L., Florida Kidney Physicians, Fort Lauderdale, Florida, United States
- Patel, Neal A., Elixia LLC, Royal Palm Beach, Florida, United States
- Hour, Billy T., Kidney Consultants Medical Group, Northridge, California, United States
- Crawford, Paul W., Associates in Nephrology, SC, Chicago, Illinois, United States
Background
DM199 is a recombinant form of the endogenous human tissue kallikrein-1 protein (KLK1) that by selectively releasing bradykinin-mediated nitric oxide, prostaglandins and other anti-inflammatory mediators to increase renal blood flow, and reduce inflammation, oxidative stress, and fibrosis in the kidney and elsewhere. The safety, efficacy, pharmacokinetics, and pharmacodynamics of DM199 is being evaluated in an open-label, Phase 2 study of patients with chronic kidney disease (CKD).
Methods
Here, enrolling three cohorts of patients all with stage 2 or 3 CKD: 1) non-diabetic African Americans with hypertension (AA/CKD); 2) patients with IgA nephropathy (IgAN); and 3) patients with type 2 diabetes mellitus with hypertension (DKD). Patients were assigned to receive subcutaneous DM199 2 or 5 mcg/kg twice weekly for 95 days. Primary endpoints were safety and tolerability, kidney function (eGFR, urine:albumin creatinine ratio [UACR], blood pressure), and plasma and urine pharmacokinetics of DM199 (and KLK1).
Results
At an interim analysis conducted June 2021, 62 patients had completed the study, and data were available for 56 patients, 12 in the AA/CKD cohort, 16 in the IgAN cohort, and 28 in the DKD cohort. Results are in the Table. DM199 was well tolerated across all cohorts, with no DM199 related severe adverse events (AEs) or discontinuations due to drug-related AEs. AEs were generally mild to moderate in severity, with the most common being local injection site irritation that resolved.
Conclusion
These data provide clinical validation of the meaningful biologic activity of the recombinant KLK1 (DM199) and support the potential of achieving clinical benefit in patients with CKD. Enrollment is continuing in the AA/CKD and IgAN cohorts.
| UACR (mg/g) | eGFR (mL/min/1.73 mg2) | Systolic/Diastolic Blood Pressure (mm Hg) | |
| Cohort 1 – AA/CKD (n=12) | |||
| Baseline | 809 | 43.3 | 147 / 91 |
| Mean Change | -8% (baseline >150) -27% (baseline >500) | 2.0 | -8 / -3 |
| Cohort 2 – IgAN (n=16) | |||
| Baseline | 988 | 39.8 | 128 / 83 |
| Mean Change | -6% (baseline >150) -3% (baseline >500) | <1.0 | 2 / <1 |
| Cohort 3 – DKD (n=28) | |||
| Baseline | 1273 | 45.8 | 144 / 80 |
| Mean Change | No change | <1.0 | -5 / 1 |
Funding
- Commercial Support – DiaMedica Therapeutics, Inc.