Abstract
Introduction: Patients with end-stage kidney disease (ESKD) exhibit anemia, chronic kidney disease‒mineral bone disorder (CKD–MBD), and cardiovascular disease. The REN-001 and REN-002 phase II, multicenter, randomized studies examined safety, tolerability, and effects of sotatercept, an ActRIIA-IgG1 fusion protein trap, on hemoglobin concentration; REN-001 also explored effects on bone mineral density (BMD) and abdominal aortic vascular calcification. Methods: Forty-three patients were treated in REN-001 (dose range: sotatercept 0.3‒0.7 mg/kg or placebo subcutaneously [s.c.] for 200 days) and 50 in REN-002 (dose range: 0.1‒0.4 mg/kg i.v. and 0.13‒0.5 mg/kg s.c. for 99 days). Results: In REN-001, frequency of achieving target hemoglobin response (>10 g/dl [6.21 mmol/l]) with sotatercept was dose-related and greater than placebo (0.3 mg/kg: 33.3%; 0.5 mg/kg: 62.5%; 0.7 mg/kg: 77.8%; 0.7 mg/kg [doses 1 and 2]/0.4 mg/kg [doses 3‒15]: 33.3%; placebo: 27.3%). REN-002 hemoglobin findings were similar (i.v.: 16.7%−57.1%; s.c.: 11.1%‒42.9%). Dose-related achievement of ≥2% increase in femoral neck cortical BMD was seen among only REN-001 patients receiving sotatercept (0.3‒0.7 mg/kg: 20.0%‒57.1%; placebo: 0.0%). Abdominal aortic vascular calcification was slowed in a dose-related manner, with a ≤15% increase in Agatston score achieved by more REN-001 sotatercept versus placebo patients (60%‒100% vs. 16.7%). The most common adverse events during treatment were hypertension, muscle spasm, headache, arteriovenous fistula site complication, and influenza observed in both treatment and placebo groups. Conclusion: In patients with ESKD, sotatercept exhibited a favorable safety profile and was associated with trends in dose-related slowing of vascular calcification. Less-consistent trends in improved hemoglobin concentration and BMD were observed.
| Original language | English |
|---|---|
| Pages (from-to) | 1585-1597 |
| Number of pages | 13 |
| Journal | Kidney International Reports |
| Volume | 4 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2019 |
Bibliographical note
Funding Information:These studies were sponsored by Celgene Corporation. The authors thank the patients and their families as well as the investigators and subinvestigators for their contributions to the studies. The authors thank Sarah Warner, PhD, of Parexel International, for her support of the methodology for capture and analysis of the qCT data presented in this report, and Theodore Reiss, MD, of Celgene Corporation, for his review of the report. The authors received editorial support in the preparation of this report from Kristin Carlin, RPh, MBA, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, sponsored by Celgene Corporation, Summit, NJ, USA. The authors, however, directed and are fully responsible for all content and editorial decisions for this report. Celgene is committed to responsible and transparent sharing of clinical trial data with patients, healthcare practitioners, and independent researchers for the purpose of improving scientific and medical knowledge as well as fostering innovative treatment approaches. For more information, please visit: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/.
Publisher Copyright:
© 2019 International Society of Nephrology
Keywords
- bone mineral density
- end-stage kidney disease
- hemoglobin
- pharmacodynamics
- sotatercept
- vascular calcification
ASJC Scopus subject areas
- Ophthalmology
- Nephrology
