Phase 1 Study of ACE-083 in Healthy Subjects
Condition: Musculoskeletal Diseases
MeSH terms: Musculoskeletal Diseases
Intervention: ACE-083
Intervention description: recombinant fusion protein
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 58.0
Sex: Female
Minimum age: 45 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Postmenopausal women, defined by follicle stimulating hormone (FSH) level > 40 IU/L
             and either 12 months of spontaneous amenorrhea or at least 6 months post-surgical
             bilateral oophorectomy and/or hysterectomy

          -  BMI 18.5-32 kg/m2

          -  Clinical laboratory values that meet the following criteria prior to dosing on Study
             Day 1: (i) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 x
             upper limit of normal (ULN), (ii) Calculated creatinine clearance ≥ 60 mL/min, (iii)
             Platelet count ≥ 100 x109/L

          -  Able to adhere to the study visit schedule, understand and comply with protocol
             requirements

          -  Understand and sign written informed consent

        Exclusion Criteria:

          -  History of hepatitis B (HBsAg and HB core Ab), human immunodeficiency virus (HIV)
             antibody or active hepatitis C

          -  Positive drug or alcohol screen test at screening or on Day 1

          -  History of drug or alcohol abuse (as defined by the Investigator) or required
             treatment for drug or alcohol use within 2 years of Day 1

          -  Donation or loss ≥ 500 mL of whole blood within 2 months prior to Day 1

          -  History of opportunistic infection (e.g., invasive candidiasis or pneumocystis
             pneumonia) within 6 months prior to screening; serious local infection (e.g.,
             cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to
             screening

          -  History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant
             proteins

          -  History of active malignancy, with the exception of fully excised or treated basal
             cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the
             skin

          -  History of clinically significant (as determined by the Investigator) cardiac,
             endocrine, hematologic, hepatic, immune, metabolic, urologic, pulmonary, neurologic,
             neuromuscular, dermatologic, psychiatric, renal, and/or other disease

          -  Treatment with systemic glucocorticoid therapy, statin medication, insulin, oral
             hormone replacement therapy or any other therapy (including investigational) with
             known or intended effects on muscle within 3 months prior to Day 1

          -  Treatment with anti-platelet, anti-coagulant, or any other therapy (including
             investigational) with known or intended effects on bleeding risk within 1 week prior
             to Day 1

          -  Treatment with another investigational drug, or approved therapy for investigational
             use within 4 weeks prior to Day 1, or if the half-life of the previous product is
             known, within 5 times the half-life prior to Day 1, whichever is longer

          -  Treatment within 3 months prior to Day 1 with any potent cytochrome P450 (CYP) 3A4/5
             inhibitors (e.g., verapamil, ketoconazole, micronazole, itraconazole, erythromycin,
             telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir,
             lopinavir, atazanavir, amprenavir, fosamprenavir, delavirdine) or CYP3A4/5 inducers
             (carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin,
             amobarbital, nevirapine, primidone, rifabutin, rifampin, St. John's wort)

          -  Subject is unwilling or unable to maintain physical activity at baseline level for the
             duration of the study

          -  Subject has any condition that would prevent MRI scanning (e.g., pacemaker, knee/hip
             replacement, metallic implant, or extreme claustrophobia)

          -  Subject is unsuitable for enrollment in the opinion of the Investigator or Sponsor for
             other unspecified reasons