A Randomized Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of the Novel Myostatin Inhibitor Apitegromab (SRK-015): A Potential Treatment for Spinal Muscular Atrophy
| Autor: | Yung Chyung, Ashish Kalra, Long Kimberly, Katherine Kacena, Ryan Iarrobino, Shaun M. Cote, Leela Vrishabhendra, James Gordon Still, Doreen Barrett, George Nomikos, Sanela Bilic, Amy Place |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Neuromuscular disease Cmax Myostatin Pharmacology Placebo Drug Administration Schedule Muscular Atrophy Spinal Pharmacokinetics Double-Blind Method Medicine Humans Phase 1 study Pharmacology (medical) Original Research biology Dose-Response Relationship Drug business.industry General Medicine Spinal muscular atrophy medicine.disease Human monoclonal antibody Tolerability SRK-015 Pharmacodynamics Area Under Curve biology.protein Apitegromab Safety business |
| Zdroj: | Advances in Therapy |
| ISSN: | 1865-8652 |
| Popis: | Introduction Apitegromab (SRK-015) is an anti-promyostatin monoclonal antibody under development to improve motor function in patients with spinal muscular atrophy, a rare neuromuscular disease. This phase 1 double-blind, placebo-controlled study assessed safety, pharmacokinetic parameters, pharmacodynamics (serum latent myostatin), and immunogenicity of single and multiple ascending doses of apitegromab in healthy adult subjects. Methods Subjects were administered single intravenous ascending doses of apitegromab of 1, 3, 10, 20, 30 mg/kg or placebo, and multiple intravenous ascending doses of apitegromab of 10, 20, 30 mg/kg or placebo. Results Following single ascending doses, the pharmacokinetic parameters of apitegromab appeared to be similar across all dose groups, following a biphasic pattern of decline in the concentration–time curve. The mean apparent terminal t1/2 after single intravenous doses of apitegromab ranged from 24 to 31 days across dose groups. Dose-related increases were observed in Cmax following multiple ascending doses. Single and multiple apitegromab doses resulted in dose-dependent and sustained increases in serum latent myostatin, indicating robust target engagement. Apitegromab was safe and well tolerated, on the basis of the adverse event (AE) profile with no clinically meaningful changes in baseline vital signs, electrocardiograms, or clinical laboratory parameters and no anti-drug antibody formation. Conclusion These results support continued investigation of apitegromab for the treatment of patients with milder forms (type 2 and 3) of spinal muscular atrophy. |
| Databáze: | OpenAIRE |
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