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Trial record 1 of 4 for:    ACE-083
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Phase 1 Study of ACE-083 in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT02257489
Recruitment Status : Completed
First Posted : October 6, 2014
Last Update Posted : May 11, 2016
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.

Tracking Information
First Submitted Date  ICMJE October 2, 2014
First Posted Date  ICMJE October 6, 2014
Last Update Posted Date May 11, 2016
Study Start Date  ICMJE September 2014
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2014)
ACE-083 safety and tolerability [ Time Frame: From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106) ]
safety/tolerability assessment, following intramuscular administration, includes adverse events, injection site reactions, laboratory measurements, vital signs, etc.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02257489 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2015)
  • ACE-083 pharmacokinetics [ Time Frame: From initiation of treatment (Study Day 1) to Study Day 92 ]
    Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle
  • ACE-083 pharmacodynamics [ Time Frame: From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106) ]
    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)
Original Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2014)
  • ACE-083 pharmacokinetics [ Time Frame: From initiation of treatment (Study Day 1) to Study Day 92 ]
    Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh muscle
  • ACE-083 pharmacodynamics [ Time Frame: From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106) ]
    Pharmacodynamic assessments include measurements of thigh volume and composition (by MRI) and muscle strength testing
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Study of ACE-083 in Healthy Subjects
Official Title  ICMJE A Phase 1, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Local Muscle Injections of ACE-083 in Healthy Postmenopausal Women
Brief 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.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Musculoskeletal Diseases
Intervention  ICMJE Drug: ACE-083
recombinant fusion protein
Study Arms  ICMJE
  • Experimental: 50 mg single dose
    8 subjects in total; 6 subjects to received ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly
    Intervention: Drug: ACE-083
  • Experimental: 100 mg single dose
    8 subjects in total; 6 subjects to received ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly
    Intervention: Drug: ACE-083
  • Experimental: 200 mg single dose
    8 subjects in total; 6 subjects to received ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly
    Intervention: Drug: ACE-083
  • Experimental: 100 mg multiple dose
    8 subjects in total; 6 subjects to received ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly
    Intervention: Drug: ACE-083
  • Experimental: 200 mg multiple dose
    8 subjects in total; 6 subjects to received ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly
    Intervention: Drug: ACE-083
  • Experimental: 100 mg (multiple dose)
    9 subjects in total; 6 subjects to received ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly
    Intervention: Drug: ACE-083
  • Experimental: 150 mg multiple dose
    9 subjects in total; 6 subjects to received ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly
    Intervention: Drug: ACE-083
Publications * Glasser CE, Gartner MR, Wilson D, Miller B, Sherman ML, Attie KM. Locally acting ACE-083 increases muscle volume in healthy volunteers. Muscle Nerve. 2018 Jun;57(6):921-926. doi: 10.1002/mus.26113. Epub 2018 Mar 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 2, 2015)
58
Original Estimated Enrollment  ICMJE
 (submitted: October 3, 2014)
40
Actual Study Completion Date  ICMJE April 2016
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 45 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02257489
Other Study ID Numbers  ICMJE A083-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Acceleron Pharma, Inc.
Study Sponsor  ICMJE Acceleron Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Manager Acceleron Pharma, Inc.
PRS Account Acceleron Pharma, Inc.
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP