A Safety, Tolerability and Pharmacodynamics Study of ACE-011 (ActRIIA-IgG1) in Healthy Postmenopausal Women

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multiple-dose, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ACE-011 in healthy postmenopausal women.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacodynamics of ACE-011 (ActRIIA-IgG1) in Healthy Postmenopausal Women

Conditions
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Osteoporosis

Intervention / Treatment
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* Biological: ACE-011 or placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a postmenopausal woman, 45-85 years old (inclusive). Subject has had 12 months of spontaneous amenorrhea, OR 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >40 IU/L OR is 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. Subject is taking at least 500 mg of calcium supplement and 400 IU of vitamin D daily and has been following this regimen for at least 4 weeks prior to the first dose of study drug administration. Subject has a body mass index (BMI) of ≥ 18.5 to < 30. Subject must give written informed consent. If required by local law, candidates must also authorize the release and use of protected health information (PHI). Exclusion Criteria: Subject has a history of clinically significant major disease (as determined by the Investigator). Subject has a history of hyperparathyroidism, hypoparathyroidism, hypocalcemia, rheumatoid arthritis, myeloproliferative disorder, gout, Paget's disease of the bone, or osteomalacia. Subject has had a long bone fracture within the past 6 months prior to enrollment, or an osteoporosis-related fracture within the previous 2 years. Subject has a history of opportunistic infection, or has had a serious local or systemic infection within 3 months prior to screening. Subject has a history of severe allergic or anaphylactic reactions. Subject had major surgery within the previous 3 months. Subject has a history of drug or alcohol abuse, or tests positive in a drug and alcohol screen at screening or on Day 1 prior to dosing. Subject consumed any alcohol within 72 hours prior to dosing. Subject gave a blood donation (one unit or more) within 1 month prior to dosing, or plans to give a blood donation during the course of the study. Subject has taken any of the following bone active medications: Teriparatide at any time in their lifetime. Fluoride therapy for more than 3 months during the previous 2 years. Estrogen, androgen, anabolic steroids, corticosteroids (excluding inhaled, topical or local injections for joint pain), calcitonin, or other bone active drugs (e.g. selective estrogen receptor modulators) within the 4 months prior to screening. Bisphosphonates: If treated for more than 6 months at any time in their lifetime. If treated for 3 to 6 months within 2 years of screening. If treated for less than 3 months within 6 months of screening. Subjects with chronic stable diseases including migraines, hypertension, hyperthyroid disorder, hypothyroid disorder, gastroesophageal reflux disease, or mild depression/anxiety will be excluded unless the investigator does not have safety or compliance concerns at study entry.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single<br>10 subjects (8 active and 2 placebo) | Biological: ACE-011 or placebo<br>* multiple administrations of ACE-011 given subcutaneously once per month for 3 months (4 administrations total)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of multiple, escalating doses of ACE-011 in healthy postmenopausal women. |  | specified timepoints in the protocol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the pharmacokinetic (PK) parameters of multiple, escalating doses of ACE-011 administered subcutaneously and to determine the effect of ACE-011 on bone mineral density (BMD) and biochemical markers of bone formation and resorption. |  | at specified timepoints in the protocol |