Abstract: INFO05-FR
A Phase 1b/2a Double-Blind, Placebo-Controlled Study of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Non-Dialysis-Dependent CKD and Anemia
Session Information
- Informational Posters - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- No subcategory defined
Authors
- Arora, Samir, Centricity Research, Columbus, Ohio, United States
- Monroy Avella, Jorge Enrique, Flourish Research, Winter Park, Florida, United States
- Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States
- Silva, Arnold L., Boise Kidney & Hypertension Institute, Meridian, Idaho, United States
- Novikov, Natasha, Disc Medicine, Watertown, Massachusetts, United States
- Buch, Akshay, Disc Medicine, Watertown, Massachusetts, United States
- Pelletier, Olivia, Disc Medicine, Watertown, Massachusetts, United States
- Savage, Will, Disc Medicine, Watertown, Massachusetts, United States
Description
Hepcidin, a central regulator of iron homeostasis, is pathologically elevated in patients with non-dialysis dependent chronic kidney disease (NDD-CKD) and anemia. Elevations in hepcidin contribute to the onset, maintenance, and severity of anemia. DISC-0974 is an investigational, first-in-class, monoclonal antibody that blocks hemojuvelin (HJV), a co-receptor in the bone morphogenetic protein-signaling pathway regulating hepcidin expression.
In a healthy volunteer study, DISC-0974 demonstrated dose-dependent reductions in serum hepcidin, increases in serum iron with doses up to 56 mg administered subcutaneously (SC), and increasing trends in reticulocyte hemoglobin, mean corpuscular hemoglobin, total hemoglobin (Hgb), and red blood cell count. In a rat model of anemia in CKD, DISC-0974 decreased hepcidin, increased serum iron, and normalized hemoglobin.
We designed a Phase 1b, double-blinded, placebo-controlled, single-ascending dose study (NCT05745883),to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DISC-0974 in patients with NDD-CKD and anemia. Eligible participants include patients >18 years of age with NDD-CKD, stages 2-5, hemoglobin (Hgb) <10.5 g/dL in women and <11.0 g/dL in men, serum ferritin ≥100 μg/L, and transferrin saturation (TSAT) ≤30%. Major exclusionary criteria include: concomitant treatment with therapeutic oral iron, intravenous iron, erythropoietin-stimulating agents or blood transfusions. Approximately 32 participants will be enrolled.
On the Day 1, participants will receive a single dose of DISC-0974 SC with evaluations for safety, PK, and PD through 57 days of follow-up. Dose-escalation is planned across 4 cohorts (n=8 each), randomized 3:1 active treatment to placebo, treated at single doses of 28, 40, 60, or 90 mg SC DISC-0974. Safety Review Committee assessments are planned to gate escalation decisions.
Primary endpoints include adverse events, clinical laboratory assessments, vital signs, physical examinations, and electrocardiograms. Secondary endpoints include changes in serum hepcidin-25, iron, TSAT, ferritin, Hgb and other hematology biomarkers.
Funding
- Disc Medicine