The purpose of the study is to assess safety, tolerance, pharmacokinetic, and pharmacodynamics of single doses of ACE-2494 in healthy postmenopausal women.
Subjects will be evaluated for study inclusion/exclusion criteria during the screening period (within 4 weeks prior to Day -1) and eligible subjects who have signed the informed consent form (ICF) will be enrolled and treated with study drug (ACE-2494 or placebo) on Day 1. Subjects will be randomized (3:1, ACE-2494: placebo) to receive one dose of either ACE-2494 or placebo, respectively, on Day 1. The primary objective of the study is to evaluate the safety and tolerability of single ascending doses of ACE-2494 in healthy postmenopausal women. The secondary objectives are to characterize the pharmacokinetic (PK) profile and pharmacodynamic (PD) effects, including serum biomarkers, fat, lean, and bone mass (DXA), muscle volume and intramuscular fat fraction (MRI).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
48
Recombination fusion protein
Syneos Health
Québec, Canada
Number of participants with ACE-2494 treatment-related adverse events as assessed by CTCAE v5.0
Adverse events (including both clinical observations and laboratory measurements), deemed related to ACE-2494 treat, will be recorded for each study subject
Time frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 85)
Determination of ACE-2494 serum Cmax
Determination of maximum serum concentration of ACE-2494 following subcutaneous administration
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Determination of ACE-2494 serum Tmax
Determination of time to maximum serum concentration of ACE-2494 following subcutaneous administration
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Determination of ACE-2494 serum T1/2
Determination of serum half-life of ACE-2494 following subcutaneous administration
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Determination of ACE-2494 AUC
Determination of the area under the serum concentration curve of ACE-2494 following subcutaneous administration
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Quantitation of serum GDF8 following ACE-2494 treatment
Quantitation of serum levels of growth differentiation factor (GDF)8 following treatment with ACE-2492
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
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Quantitation of serum BSAP following ACE-2494 treatment
Quantitation of serum levels of bone-specific alkaline phosphatase (BSAP) following treatment with ACE-2494
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Quantitation of serum CTX following ACE-2494 treatment
Quantitation of serum levels of carboxy-terminal collagen crosslinks (CTX) following treatment with ACE-2494
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Quantitation of serum FSH following ACE-2494 treatment
Quantitation of serum levels of follicle stimulating hormone (FSH) following treatment with ACE-2494
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Determination of body composition following ACE-2494 treatment by DXA
Regional and whole-body quantitation of fat mass by dual energy X-ray absorptiometry (DXA) following treatment with ACE-2494
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Determination of body composition following ACE-2494 treatment by DXA
Regional and whole-body quantitation of lean mass by dual energy X-ray absorptiometry (DXA) following treatment with ACE-2494
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Determination of body composition following ACE-2494 treatment by DXA
Regional and whole-body quantitation of bone mass by dual energy X-ray absorptiometry (DXA) following treatment with ACE-2494
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Determination of thigh muscle volume and intramuscular fat following ACE-2494 treatment by MRI for patients in Cohorts 4-6 only
Determination of total muscle volume in the thigh by magnetic resonance imaging (MRI)
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)
Determination of thigh muscle volume and intramuscular fat following ACE-2494 treatment by MRI for patients in Cohorts 4-6 only
Determination of intramuscular fat in the thigh by magnetic resonance imaging (MRI)
Time frame: From initiation of treatment, Study Day (SD)1 to end of follow-up period (SD85)