Phase 1b Study of DM199 in Patients with Diabetes and CKD

DM199, a recombinant form of endogenous human tissue kallikrein protein (KLK₁), restores KLK₁ levels and enables selective release of bradykinin-mediated nitric oxide, prostaglandin, and other anti-inflammatory mediators to improve renal blood flow, inflammation, oxidative stress, and fibrosis. During a presentation at the NKF Spring Clinical Meetings, Thomas Marbury, MD, and colleagues reported results of a phase 1b study designed to examine the safety, tolerability, and pharmacokinetics of DM199 in patients with diabetes and chronic kidney disease (CKD).  The presentation was titled Open-label Study of the Pharmacokinetics , Safety, and Tolerability of DM199 in Subjects with Diabetes and Chronic Kidney Disease.

The study included two cohorts of patients with type 1 or type 2 diabetes and CKD stage 3 or 4. Cohort one received a subcutaneous dose of DM 199 of 3, 5, or 8 mg/kg. Cohort two received a subcutaneous dose of DM199 3 mg/kg. The safety assessment was based on adverse events, vital signs, clinical laboratory testing, and electrocardiogram (ECG).

A total of 33 patients completed the study; of those, 25 had moderate CKD and eight had severe CKD. Common adverse events were orthostatic hypotension/hypotension (30.3%), diarrhea (9.1%), injection site events (18.2%), and headache (12.15). There were no discontinuations of study drugs related to adverse events, no serious adverse events, and no changes in laboratory, blood pressure, or ECG findings observed.

DM199 exhibited dose-proportional pharmacokinetics. At 24 hours, there were increases in nitric oxide (35.2%) and prostaglandin E₂ (41.2%). Estimated glomerular filtration rate (eGFR) increased by 4.08 mL/min/1.73 m² and urine albumin-to-creatinine ratio (UACR) decreased by 18.7%.

In summary, the researchers said, “DM199 was well tolerated with most adverse events at 8 mg/kg. The pharmacokinetic profile was dose-proportional and consistent with results from previous studies. DM199 single dose showed encouraging results with an increased eGFR and decreased UACR at 24 hours.”

Source: Marbury T, Alcorn H, Bakris G, et al. Open-label study of the pharmacokinetics, safety, and tolerability of DM199 in subjects with diabetes and chronic kidney disease. Abstract of a presentation at the National Kidney Foundation 2020 Spring Clinical Meetings; abstract #310.