This study will evaluate the safety and tolerability of single and multiple doses of ACE-083 as a local injection into selected skeletal muscles of healthy subjects. The study will also determine the amount of ACE-083 that reaches the systemic circulation following local administration. Additionally, the study will assess whether local administration into skeletal muscle results in an increase in the size and/or strength of the injected muscle.
ACE-083 is a molecule that has been shown to increase skeletal muscle mass in animals and, therefore, has potential utility in certain diseases that affect skeletal muscle. This initial study in healthy human subjects will help determine the properties of ACE-083 (safety, tolerability, drug absorption and biologic activity), following local administration into skeletal muscle, in advance of clinical trials in patients. The study will consist of up to 7 planned groups of 8 or 9 subjects each. Subjects in each cohort will be randomized to receive either ACE-083 or placebo. ACE-083 (or placebo) will be administered locally into the right quadriceps (thigh) muscle or right tibialis anterior (lower leg) muscle. Subjects will receive a total of either one dose (on Day 1) or two doses (on Day 1 and Day 22). Each dose administered could include up to 4 injections of study drug into pre-defined locations in the muscle. A Safety Review Team (SRT) will review blinded, preliminary data from each treatment group to make recommendations regarding escalation to the next treatment group. Subjects will be assessed for safety throughout the treatment and follow-up periods. Follow-up visits will occur over 12 weeks following the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
58
recombinant fusion protein
Acceleron Investigative Site
Lincoln, Nebraska, United States
ACE-083 Safety and Tolerability: Number of Subjects With Adverse Events
Safety/tolerability assessment, following intramuscular administration, includes adverse events, injection site reactions, laboratory measurements, vital signs, etc.
Time frame: From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)
ACE-083 Pharmacokinetics: Maximum Measured Plasma Concentrations
Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle
Time frame: PK samples were collected predose, and at 3 hours and 6 hours postdose.
ACE-083 Pharmacodynamics
Pharmacodynamic assessments include measurements of thigh or lower leg volume and composition (by MRI) and muscle strength testing (by hand-held dynamometer and fixed system)
Time frame: From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)
ACE-083 Pharmacokinetics: Time of the Maximum Measured Plasma Concentration
Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle
Time frame: PK samples were collected predose, and at 3 hours and 6 hours postdose.
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