A Safety, Tolerability and Efficacy Study of ACE-011 in Patients With Osteolytic Lesions of Multiple Myeloma

Study Overview
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Brief Summary
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Multi-center, randomized, multiple-dose study to evaluate the safety, tolerability and efficacy of ACE-011 in patients with osteolytic lesions of multiple myeloma.

Official Title
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A Phase 2a, Multi-Center, Randomized, Multiple-Dose Study to Evaluate the Safety, Tolerability and Efficacy of ACE-011 (hActRIIA-IgG1) in Patients With Osteolytic Lesions of Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: ACE-011
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patient at least 18 years of age with stage II or III multiple myeloma One or more lytic bone lesions If currently receiving bisphosphonate therapy, have been on a stable dose for ≥ 2 months before dosing day 1 or must not have received bisphosphonates within 2 months of dosing day 1 If patient has undergone previous autologous or allogenic hematopoietic stem cell transplantation (HSCT), they must be stable (in the opinion of the investigator) and be a minimum of 6 months since HSCT Has planned HSCT for the duration of the study Has moles or lesions that are currently undiagnosed, but are suspect for malignancy Has an underlying condition that may result in abnormal bone metabolism other than cancer related bone lesions, such as a history of hyperparathyroidism, hypoparathyroidism, hypocalcemia, rheumatoid arthritis, myeloproliferative disorder, gout, Paget's disease of the bone, or osteomalacia; patients with a diagnosis of osteoporosis prior to multiple myeloma diagnosis are eligible to participate. Key Exclusion Criteria: Known underlying condition that may result in abnormal bone metabolism other than cancer related bone lesions History of polyneuropathy ≥ grade 3 Patients with plasma cell leukemia Planned stem cell transplant (HSCT) or radiation for the duration of the study Skeletal related event within 2 weeks of study enrollment Has received erythropoiesis-stimulating agents (ESAs) within the last 21 days or is planned to receive ESAs during the course of the study Has received anti-myeloma therapy within the last 21 days Is scheduled to receive local radiation to bone during the course of the study Has taken estrogen, androgen, anabolic steroids, calcitonin or other bone-active drugs within 4 months of study enrollment Woman of childbearing potential (not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subcutaneous injection on days 1, 29, 57 and 85. | Biological: Placebo<br>* Placebo given by the subcutaneous route of administration monthly for 4 doses.<br>|
| Experimental: ACE-011 0.1 mg/kg<br>Subcutaneous injection of ACE-011 0.1 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85). | Biological: ACE-011<br>* ACE-011 given by the subcutaneous route of administration monthly for 4 doses.<br>* Other names: hActRIIA-IgG1;|
| Experimental: ACE-011 0.3 mg/kg<br>Subcutaneous injection of ACE-011 0.3 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85). | Biological: ACE-011<br>* ACE-011 given by the subcutaneous route of administration monthly for 4 doses.<br>* Other names: hActRIIA-IgG1;|
| Experimental: ACE-011 0.5 mg/kg<br>Subcutaneous injection of ACE-011 0.5 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85). | Biological: ACE-011<br>* ACE-011 given by the subcutaneous route of administration monthly for 4 doses.<br>* Other names: hActRIIA-IgG1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with Treatment-emergent Adverse Experiences |  | Up to Day 169 | 
| Change from baseline at end of treatment in Bone Specific Alkaline Phosphatase (BSAP) | BSAP is a biomarker of bone formation. | Up to Day 169 | 
| Change from baseline at end of treatment in Serum intact procollagen type I N terminal propeptide (PINP) | PINP is a biomarker of bone formation. | Up to Day 169 | 
| Change from Baseline at End of Treatment in Serum C-terminal type I collagen telopeptide (CTX) | CTX is a bone resorption biomarker. | Up to Day 169 | 
| Change from Baseline at End of Treatment in Serum tartrate-resistant acid phosphatase isoform-5b (Tracp-5b) | Tracp-5b is a bone resorption biomarker. | Up to Day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline at End of Treatment in Hip Bone Mineral Density |  | Up to Day 169 | 
| Change from Baseline at End of Treatment in Lumbar Spine Bone Mineral Density |  | Up to Day 169 | 
| Summary of Investigator's Bone Lesion Assessment Based on Skeletal X-rays During Follow-up |  | Up to Day 169 | 
| Change from Baseline to End of Treatment in Participant-reported Bone Pain Assessment Using a Visual Analog Scale (VAS) Score |  | Up to Day 169 | 
| Participants with Skeletal-related Adverse Events |  | Up to Day 169 | 
| Pharmacokinetics - AUC | Area under the plasma concentration-time curve | Up to Day 169 | 
| Pharmacokinetics - Cmax | Maximum observed concentration | Up to 169 days | 
| Pharmacokinetics - Tmax | Time to maximum observed concentration | Up to 169 days | 
| Pharmacokinetics - t½ | Elimination half-life | Up to 169 days | 
| Pharmacokinetics - λz | Elimination rate constant | Up to 169 days | 
| Pharmacokinetics - Vz/F | Volume of distribution | Up to 169 days | 
| Pharmacokinetics - CL/F | Total clearance | Up to 169 days | 
| Pharmacokinetics - Ka | Absorption rate constant | Up to 169 days |