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Kidney Week

Abstract: PO0066

Biomarker and Safety Results from a Phase 1b Study of RBT-9 in Healthy Volunteers and Subjects with CKD Stage 3/4

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Zager, Richard A., Fred Hutchinson Cancer Research Center, Seattle, Washington, United States
  • Singh, Bhupinder, Renibus Therapeutics, Southlake, Texas, United States
  • Guillem, Alvaro F., Renibus Therapeutics, Southlake, Texas, United States
  • Goldstein, Stuart, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background

Acute kidney injury (AKI) remains a major unmet medical need without any FDA approved preventive or therapeutic options. Safe administration of pharmacologic agents that can prevent AKI in the hospital setting have great potential given the high rate of AKI-related morbidity and mortality. Organ preconditioning to elicit a state of induced cytoresistance prior to insult, such as cardiac surgery, is a mechanism by which the drug RBT-1 has been shown to be protective in various animal models of AKI including glycerol-induced rhabdomyolysis, maleate-induced hypoxic/ischemic renal injury, and ischemia reperfusion injury.

RBT-1 is composed of proprietary formulations of stannous protoporphyrin (RBT-9) and iron sucrose (RBT-3). We conducted three phase 1 clinical trials to study the effect of RBT-1, RBT-3, and RBT-9 on biomarkers of cytoprotection observed in experimental animals and on clinical safety. Herein, we report results from the Phase 1b study of RBT-9 in both healthy volunteers and subjects with CKD Stage 3/4.

Methods

Forty-two subjects were enrolled and received a single dose of RBT-9 at 9 mg (N=6), 27 mg (N=18), and 90 mg (N=18). None of the subjects in the 9 mg group had CKD; 12 subjects (67%) in each of the 27 and 90 mg groups had CKD. Mean age was 59.5 years.

Results

RBT 9 dose-dependently induced cytoprotective biomarker responses (heme oxygenase-1 [HO-1], ferritin, NAD[P]H dehydrogenase [quinone] 1 [NQO1], and interleukin-10 [IL-10]) in both healthy volunteers and CKD subjects.

Treatment-emergent adverse events (TEAEs) were reported in 20 subjects (47%), the majority of which were photosensitivity events and largely confined to the 90 mg treatment group. TEAEs were generally mild in severity. Only 3 TEAEs were moderate; no TEAEs were severe. No serious adverse events were reported. All TEAEs resolved during follow-up. There was no evidence of renal injury, as assessed by albuminuria and various biomarkers of renal tubular injury (KIM-1, NGAL, cystatin C, NAG).

Conclusion

We conclude that RBT-9 was safe and well tolerated in healthy volunteers and subjects with CKD. Adverse events were generally mild and related to photosensitivity reactions. Dose-dependent cytoprotective protein responses were observed that have previously corresponded with AKI protection in experimental animals.

Funding

  • Commercial Support