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Kidney Week

Abstract: INFO13

Phase 1, Randomized, Controlled Trial of GFB-024 in Healthy Overweight and Obese Participants and in Participants With Type 2 Diabetes Mellitus

Session Information

  • Informational Posters
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

  • No subcategory defined

Authors

  • Gaich, Gregory A., Goldfinch Bio Inc, Cambridge, Massachusetts, United States
  • Lawler, John, Goldfinch Bio Inc, Cambridge, Massachusetts, United States
  • Dagon, Yossi, Goldfinch Bio Inc, Cambridge, Massachusetts, United States
  • Gustafson, Thomas A., Goldfinch Bio Inc, Cambridge, Massachusetts, United States
  • Johnson, Leslie, Goldfinch Bio Inc, Cambridge, Massachusetts, United States
  • Rudolph-Owen, Lori, Goldfinch Bio Inc, Cambridge, Massachusetts, United States
Description

Evidence from nonclinical studies suggests a role of cannabinoid-1 receptor (CB1) in the development of diabetic nephropathy (DN). Kidney CB1 expression is upregulated in podocytes and tubular cells in murine models of obesity and diabetes mellitus (DM). Inhibition by CB1 inverse agonists have been shown to ameliorate diabetes-induced albuminuria, inhibit kidney fibrosis and inflammation, and prevent podocyte damage and dysfunction. Nonclinical mouse models of DM have shown that genetic deletion of CB1 specifically in podocytes protects against hyperglycemia-induced glomerular dysfunction and proximal tubular injury.

GFB-024 is a recombinant humanized monoclonal antibody functioning as a specific inverse agonist for CB1. Pharmacodynamic studies demonstrated that GFB-024 protects human podocytes in vitro and in vivo. Targeting the CB1 pathway with GFB-024 has the potential to be a novel approach in protecting podocytes from injury in patients with CB-1 associated DN.

This is a phase 1, randomized, double-blind, placebo-controlled trial with a single ascending dose (SAD) component to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of GFB-024 in up to 56 healthy overweight and obese (BMI 25 – 50 kg/m2) participants and a repeat-dose component in up to 10 participants with T2DM. (NCT04880291).

This trial is intended to 1) establish safety, tolerability, and pharmacokinetics (PK) for up to 28 days of relevant exposure in the SAD component of the study in healthy overweight and obese participants, 2) obtain PK, safety, and tolerability data in participants with T2DM, and 3) explore potential phenotypic, genotypic, and biochemical approaches to identify patients most likely to respond to GFB-024.

Participants in the SAD cohort will receive either a single dose of GFB-024 or placebo subcutaneously (SQ) starting at 5mg with half-log dose escalation up to 6 dose cohorts. Participants in the repeat-dose cohorts will receive either GFB-024 or placebo for 4 weeks with dosing regimen based on PK results from the SAD cohorts. The duration of the study is up to 18 weeks.

Results from this trial will provide the foundational evidence to support the clinical development of GFB-024 in patients with DN driven by CB1 activation.

Funding

  • Goldfinch Bio