Abstract: PO0241
RBT-1 Safety and Cytoprotective Response Biomarkers in Healthy Volunteers and Subjects with CKD
Session Information
- AKI: Clinical, Outcomes, and Trials
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Singh, Bhupinder, University of California Irvine, Irvine, California, United States
- Goldstein, Stuart, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- Tangri, Navdeep, University of Manitoba, Winnipeg, Manitoba, Canada
- Zager, Richard A., University of Washington, Seattle, Washington, United States
Background
RBT-1 (stannous protoporphyrin [SnPP] with iron sucrose [FeS]) is a novel drug designed to precondition organs to prevent acute injury via activation of Nrf2, anti-inflammatory, and iron sequestering pathways. Pretreatment with RBT-1 in several animal models of acute kidney injury (AKI) has demonstrated protection from AKI in conjunction with upregulation of cytoprotective proteins. Here, we report results of a Phase 1b study of RBT-1 that assessed safety and cytoprotective response biomarker induction in healthy volunteers and subjects with stage 3 and 4 chronic kidney disease (CKD).
Methods
Fifty-four (54) subjects (18 healthy volunteers and 36 subjects with CKD) were enrolled and received a single IV dose of RBT-1 (9, 27, 45, 63, or 90 mg SnPP with 240 mg FeS). Plasma heme oxygenase-1 (HO-1), interleukin-10 (IL-10) and ferritin were selected as surrogate measures of organ protective activity. Safety was assessed through Day 29, and cytoprotective response biomarkers were assessed through 168 hours post-dose.
Results
RBT-1 was well tolerated in both healthy volunteers and subjects with CKD. The most common treatment-emergent adverse event was photosensitivity reaction (a known reaction to SnPP), which occurred in 15 subjects (27.8%) and was more commonly observed in the higher dose groups (63 and 90 mg SnPP/240 mg FeS). Photosensitivity was transient and generally mild in intensity. No serious adverse events were reported. RBT-1 induced dose-dependent, statistically significant increases in cytoprotective response biomarkers in both healthy volunteers and subjects with CKD. Peak increases from baseline in healthy volunteers and subjects with CKD were: 386% and 402% for HO-1, respectively; 99% and 332% for IL-10, respectively; and 1552% and 469% for ferritin, respectively.
Conclusion
RBT-1 is well tolerated with a similar safety profile in healthy volunteers and subjects with CKD Stage 3 or 4 and elicits a biomarker response in humans that is associated with RBT-1-mediated organ protection in animal models of AKI. The positive safety and biomarker efficacy data provide a strong scientific basis to study RBT-1 as an AKI prevention strategy in patients undergoing elective cardiac surgery.
Funding
- Commercial Support –