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Kidney Week

Abstract: TH-PO432

A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Cohort Dose-Escalation Study of a Human Monoclonal Antibody to IL-6 in Patients with CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Nowak, Kristen L., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Chonchol, Michel, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Kakkar, Rahul, Corvidia Therapeutics, Waltham, Massachusetts, United States
  • Devalaraja, Matt, Corvidia Therapeutics, Waltham, Massachusetts, United States
  • Lo, Larry, Corvidia Therapeutics, Waltham, Massachusetts, United States
  • Kling, Douglas F., Corvidia Therapeutics, Waltham, Massachusetts, United States
Background

Chronic systemic inflammation is highly prevalent in patients with CKD (measured as an elevated high-sensitivity C-reactive protein [hsCRP]) and independently associated with cardiovascular events and mortality. Use of an interleukin-6 (IL-6) blocker to suppress inflammation represents a potential new paradigm to reduce cardiovascular risk in patients with CKD.

Methods

COR-001 is a fully human monoclonal antibody against IL-6. A phase I trial of COR-001 was conducted in patients with moderate-to-severe non-dialysis dependent CKD (estimated glomerular filtration rate [eGFR] 20-60 ml/min/1.73 m2) and evidence of chronic inflammation (hsCRP] level >2 mg/L over two consecutive measurements). Three cohorts of n=4 (3:1 active vs. placebo) were randomized in a blinded fashion to a single dose of COR-001 (5 mg, 15 mg, and 50 mg subcutaneous injection) and followed for 12 weeks for safety, and pharmacokinetic and pharmacodynamics assessments.

Results

Participants were 67±11 years with a baseline eGFR of 40±13 ml/min/1.73 m2 and hsCRP of 5.1±2.6 mg/L. Throughout the 12-week study period, dose escalation was approved and all adverse events were within the expected range for a CKD population selected based on the presence of inflammation. hsCRP levels were substantially reduced with COR-001 treatment. 100% of participants achieved suppression of hsCRP to < 2mg/L with the 15 mg and 50 mg dose, and several subjects had undetectable levels of hsCRP with the 50 mg dose (Figure). No SAEs were reported in any cohort . The pharmacokinetic data suggested a half-life of 38-52 days in these patients.

Conclusion

IL-6 inhibition with COR-001 was safe and highly effective at suppressing hsCRP over a long period with a single injection, in adults with moderate-to-severe CKD and evidence of chronic inflammation.

Funding

  • Commercial Support