Bone Abstracts

Objectives: To assess the safety, tolerability and pharmacokinetic (PK) profile of single and multiple doses of TA-46 administered subcutaneously to healthy volunteers.

Methods: This was a double-blind, randomized, placebo-controlled trial in a total of 72 subjects. Cohorts of 8 subjects were randomised to receive either TA-46 or placebo in a 3:1 ratio in single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. SAD doses were 0.3, 1, 3, 10 and 20 mg/kg. MAD cohorts received 4 weeks of treatment either twice weekly (1 mg/kg, 3 mg/kg) or once weekly (3 mg/kg, 10 mg/kg) subcutaneously (s.c.). The study was approved by the local research ethics committee.

Results: All doses of TA-46 were safe and well tolerated. No serious adverse events (SAEs) were reported. TA-46 related AEs were injection site reactions (ISRs), of which over 90% were mild. PK analysis showed Cmax at 48–96 h and t1/2 of 48–93 h. The PK of TA-46 after single and multiple s.c. administrations is approximately dose proportional in the range 0.3–3 mg/kg and can be described by a one-compartment PK model.

Conclusions: Single and multiple s.c. doses of TA-46 were safe and well tolerated. Mild ISRs were seen in once weekly dosing which, alongside the PK analysis, supports a once weekly dosing regimen of TA-46 in achondroplasia.

Disclosure: All authors are employees of Therachon AG.