First-In-Human Study to Assess the Pharmacokinetics and Safety of DS-6016a After Single Subcutaneous Injection in...

Area of Science:

• Pharmacology
• Immunology
• Genetics

Background:

• Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder caused by activin receptor-like kinase 2 (ALK2) mutations.
• Effective prophylactic therapies are needed for FOP, highlighting the importance of novel treatment strategies.

Purpose of the Study:

• To evaluate the pharmacokinetics and safety of DS-6016a, a humanized monoclonal anti-ALK2 antibody.
• To assess the safety and tolerability of single subcutaneous doses of DS-6016a in healthy Japanese adults.

Main Methods:

• A single-center, randomized, double-blind, placebo-controlled study.
• Healthy male Japanese adults received single subcutaneous doses of DS-6016a (5-1000 mg) or placebo in cohorts.
• Pharmacokinetic parameters, adverse events, and changes in ferritin and serum iron were monitored.

Main Results:

• DS-6016a exhibited median times to maximum plasma concentration of 144-240 hours and elimination half-lives of 391-844 hours.
• Exposure to DS-6016a was greater than dose-proportional across the tested range.
• Treatment-emergent adverse events were mild, with a lower incidence in DS-6016a groups (11%) compared to placebo (17%); no serious adverse events were reported.

Conclusions:

• DS-6016a demonstrated an acceptable safety profile in healthy adults at single subcutaneous doses from 5 to 1000 mg.
• The study provides a foundation for further investigation of DS-6016a as a potential prophylactic therapy for Fibrodysplasia Ossificans Progressiva.