CompletedNCT02257489Updated Sep 23, 2022Results posted

Phase 1 Study of ACE-083 in Healthy Subjects

A Phase 1 interventional study of ACE-083 in Musculoskeletal Diseases, sponsored by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA. Completed at 1 site in United States. Open to female participants aged 45 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-09-23.

Sponsored by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 58
Allocation: Randomized
Ages: 45 Years to 75 Years
Sex: Female

Study 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.

Read the 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.

Conditions studied

Musculoskeletal Diseases

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Musculoskeletal Diseases 657

In context

Musculoskeletal Diseases

657 studies on the registry are indexed under Musculoskeletal Diseases; 159 are open to participants now.

This study's enrollment of 58 is below the median of 73 across 438 interventional studies indexed under Musculoskeletal Diseases.

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Lead sponsor

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA is the lead sponsor of 25 studies on the registry; none are open to participants now.

Of its 8 completed or terminated interventional studies of FDA-regulated products, 7 (88%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 45 Years to 75 Years
Sexes eligible: Female
Accepts healthy volunteers: Yes

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

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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 58 participants (actual)

Study arms

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
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
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
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
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
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
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
Drug: ACE-083

Interventions

DrugACE-083
recombinant fusion protein

What researchers measure

Primary outcomes

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)

Secondary outcomes

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.

Results

Posted Jul 8, 2019

Participant flow

Participant flow — Overall Study
Milestone	50 mg Single Dose (RF)	100 mg Single Dose (RF)	200 mg Single Dose (RF)	100 mg Multiple Dose (RF)	200 mg Multiple Dose (RF)	100 mg Multiple Dose (TA)	150 mg Multiple Dose (TA)	Pooled Placebo (RF)	Pooled Placebo (TA)
Started	6	6	6	6	6	6	6	10	6
Completed	6	6	6	5	6	6	6	10	6
Not completed	0	0	0	1	0	0	0	0	0
Withdrew: Withdrawal by subject	0	0	0	1	0	0	0	0	0

Outcome measures

PrimaryACE-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)
Reported as:: Count of participants · Participants

ACE-083 Safety and Tolerability: Number of Subjects With Adverse Events
Participants	50 mg Single Dose (RF)	100 mg Single Dose (RF)	200 mg Single Dose (RF)	100 mg Multiple Dose (RF)	200 mg Multiple Dose (RF)	100 mg Multiple Dose (TA)	150 mg Multiple Dose (TA)	Pooled Placebo (RF)	Pooled Placebo (TA)
ACE-083 Safety and Tolerability: Number of Subjects With Adverse Events	6	6	6	6	6	6	6	10	6

SecondaryACE-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.
Reported as:: Number · ng/mL (Cmax)

ACE-083 Pharmacokinetics: Maximum Measured Plasma Concentrations
ng/mL (Cmax)	50 mg Single Dose (RF)	100 mg Single Dose (RF)	200 mg Single Dose (RF)	100 mg Multiple Dose (RF)	200 mg Multiple Dose (RF)	100 mg Multiple Dose (TA)	150 mg Multiple Dose (TA)
Cmax (min) dose 1	0	0	0	0	0	0	0
Cmax (max) dose 1	0	168	226	112	219	132	136

SecondaryACE-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)

Results for this outcome have not been posted.

SecondaryACE-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.
Reported as:: Number · h (Tmax)

ACE-083 Pharmacokinetics: Time of the Maximum Measured Plasma Concentration
h (Tmax)	50 mg Single Dose (RF)	100 mg Single Dose (RF)	200 mg Single Dose (RF)	100 mg Multiple Dose (RF)	200 mg Multiple Dose (RF)	100 mg Multiple Dose (TA)	150 mg Multiple Dose (TA)
Tmax (min) dose 1	0	96	96	96	600	24.00	96.0
Tmax (max) dose 1	0	96	168	96	600	96.0	96.0

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
50 mg Single Dose (RF)	—	0/6 (0%)	6/6 (100%)
100 mg Single Dose (RF)	—	0/6 (0%)	6/6 (100%)
200 mg Single Dose (RF)	—	0/6 (0%)	6/6 (100%)
100 mg Multiple Dose (RF)	—	0/6 (0%)	6/6 (100%)
200 mg Multiple Dose (RF)	—	0/6 (0%)	6/6 (100%)
100 mg Multiple Dose (TA)	—	0/6 (0%)	6/6 (100%)
150 mg Multiple Dose (TA)	—	0/6 (0%)	6/6 (100%)
Pooled Placebo (RF)	—	0/10 (0%)	10/10 (100%)
Pooled Placebo (TA)	—	0/6 (0%)	6/6 (100%)

Most frequent other events

Showing 10 of 71

Most frequent other events
Event	50 mg Single Dose (RF)	100 mg Single Dose (RF)	200 mg Single Dose (RF)	100 mg Multiple Dose (RF)	200 mg Multiple Dose (RF)	100 mg Multiple Dose (TA)	150 mg Multiple Dose (TA)	Pooled Placebo (RF)	Pooled Placebo (TA)
Injection site painGeneral disorders	5/6	5/6	6/6	5/6	6/6	5/6	6/6	10/10	6/6
Pain in extremityMusculoskeletal and connective tissue disorders	0/6	0/6	1/6	4/6	2/6	6/6	6/6	2/10	5/6
ArthralgiaMusculoskeletal and connective tissue disorders	0/6	1/6	0/6	1/6	1/6	1/6	1/6	1/10	4/6
HeadacheNervous system disorders	3/6	1/6	2/6	3/6	0/6	4/6	2/6	1/10	1/6
Injection site haemorrhageGeneral disorders	1/6	0/6	1/6	0/6	3/6	1/6	0/6	0/10	0/6
Injection site reactionGeneral disorders	0/6	0/6	1/6	1/6	3/6	0/6	1/6	1/10	0/6
Injection site discomfortGeneral disorders	0/6	1/6	0/6	3/6	0/6	3/6	1/6	1/10	3/6
Muscle twitchingMusculoskeletal and connective tissue disorders	0/6	1/6	2/6	3/6	2/6	0/6	0/6	3/10	0/6
MyalgiaMusculoskeletal and connective tissue disorders	1/6	0/6	3/6	1/6	2/6	1/6	1/6	0/10	0/6
Musculoskeletal stiffnessMusculoskeletal and connective tissue disorders	0/6	0/6	0/6	3/6	1/6	0/6	2/6	1/10	1/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)	50 mg Single Dose (RF)	100 mg Single Dose (RF)	200 mg Single Dose (RF)	100 mg Multiple Dose (RF)	200 mg Multiple Dose (RF)	100 mg Multiple Dose (TA)	150 mg Multiple Dose (TA)	Pooled Placebo (RF)	Pooled Placebo (TA)	Total
Mean	58.0 ± 4.29	54.2 ± 9.99	55.0 ± 2.37	55.2 ± 3.71	57.0 ± 2.45	55.7 ± 3.08	57.0 ± 4.73	59.2 ± 5.53	56.7 ± 7.50	56.6 ± 5.2

Sex: Female, Male
Sex: Female, Male(Participants)	50 mg Single Dose (RF)	100 mg Single Dose (RF)	200 mg Single Dose (RF)	100 mg Multiple Dose (RF)	200 mg Multiple Dose (RF)	100 mg Multiple Dose (TA)	150 mg Multiple Dose (TA)	Pooled Placebo (RF)	Pooled Placebo (TA)	Total
Female	6	6	6	6	6	6	6	10	6	58
Male	0	0	0	0	0	0	0	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	50 mg Single Dose (RF)	100 mg Single Dose (RF)	200 mg Single Dose (RF)	100 mg Multiple Dose (RF)	200 mg Multiple Dose (RF)	100 mg Multiple Dose (TA)	150 mg Multiple Dose (TA)	Pooled Placebo (RF)	Pooled Placebo (TA)	Total
Hispanic or Latino	0	1	0	1	0	1	0	0	0	3
Not Hispanic or Latino	6	5	6	5	6	5	6	10	6	55
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	50 mg Single Dose (RF)	100 mg Single Dose (RF)	200 mg Single Dose (RF)	100 mg Multiple Dose (RF)	200 mg Multiple Dose (RF)	100 mg Multiple Dose (TA)	150 mg Multiple Dose (TA)	Pooled Placebo (RF)	Pooled Placebo (TA)	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	1	0	0	0	0	1	2
White	6	6	6	5	6	6	6	10	5	56
More than one race	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0

Study locations

1 site

Acceleron Investigative Site
Lincoln, Nebraska 68502, United States

References and documents

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. PubMed 29486514 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 23, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02257489
Lead sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Responsible party: Sponsor
First posted: Oct 6, 2014
Start date: Sep 2014
Primary completion: Mar 2016
Completion: Apr 2016
Results posted: Jul 8, 2019
Last update: Sep 23, 2022

Study contacts

Clinical Trials Manager

study director · Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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