Back to resultsA Safety, Tolerability and Efficacy Study of ACE-011 in Patients With Osteolytic Lesions of Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
ACE-011
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
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)
Sites / Locations
- Investigative Site
- Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo
ACE-011 0.1 mg/kg
ACE-011 0.3 mg/kg
ACE-011 0.5 mg/kg
Arm Description
Subcutaneous injection on days 1, 29, 57 and 85.
Subcutaneous injection of ACE-011 0.1 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).
Subcutaneous injection of ACE-011 0.3 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).
Subcutaneous injection of ACE-011 0.5 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).
Outcomes
Primary Outcome Measures
Participants with Treatment-emergent Adverse Experiences
Change from baseline at end of treatment in Bone Specific Alkaline Phosphatase (BSAP)
BSAP is a biomarker of bone formation.
Change from baseline at end of treatment in Serum intact procollagen type I N terminal propeptide (PINP)
PINP is a biomarker of bone formation.
Change from Baseline at End of Treatment in Serum C-terminal type I collagen telopeptide (CTX)
CTX is a bone resorption biomarker.
Change from Baseline at End of Treatment in Serum tartrate-resistant acid phosphatase isoform-5b (Tracp-5b)
Tracp-5b is a bone resorption biomarker.
Secondary Outcome Measures
Change from Baseline at End of Treatment in Hip Bone Mineral Density
Change from Baseline at End of Treatment in Lumbar Spine Bone Mineral Density
Summary of Investigator's Bone Lesion Assessment Based on Skeletal X-rays During Follow-up
Change from Baseline to End of Treatment in Participant-reported Bone Pain Assessment Using a Visual Analog Scale (VAS) Score
Participants with Skeletal-related Adverse Events
Pharmacokinetics - AUC
Area under the plasma concentration-time curve
Pharmacokinetics - Cmax
Maximum observed concentration
Pharmacokinetics - Tmax
Time to maximum observed concentration
Pharmacokinetics - t½
Elimination half-life
Pharmacokinetics - λz
Elimination rate constant
Pharmacokinetics - Vz/F
Volume of distribution
Pharmacokinetics - CL/F
Total clearance
Pharmacokinetics - Ka
Absorption rate constant
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00747123
Brief Title
A Safety, Tolerability and Efficacy Study of ACE-011 in Patients With Osteolytic Lesions of Multiple Myeloma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
September 1, 2008 (Actual)
Primary Completion Date
August 1, 2009 (Actual)
Study Completion Date
August 1, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Multi-center, randomized, multiple-dose study to evaluate the safety, tolerability and efficacy of ACE-011 in patients with osteolytic lesions of multiple myeloma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subcutaneous injection on days 1, 29, 57 and 85.
Arm Title
ACE-011 0.1 mg/kg
Arm Type
Experimental
Arm Description
Subcutaneous injection of ACE-011 0.1 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).
Arm Title
ACE-011 0.3 mg/kg
Arm Type
Experimental
Arm Description
Subcutaneous injection of ACE-011 0.3 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).
Arm Title
ACE-011 0.5 mg/kg
Arm Type
Experimental
Arm Description
Subcutaneous injection of ACE-011 0.5 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).
Intervention Type
Biological
Intervention Name(s)
ACE-011
Other Intervention Name(s)
hActRIIA-IgG1
Intervention Description
ACE-011 given by the subcutaneous route of administration monthly for 4 doses.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo given by the subcutaneous route of administration monthly for 4 doses.
Primary Outcome Measure Information:
Title
Participants with Treatment-emergent Adverse Experiences
Time Frame
Up to Day 169
Title
Change from baseline at end of treatment in Bone Specific Alkaline Phosphatase (BSAP)
Description
BSAP is a biomarker of bone formation.
Time Frame
Up to Day 169
Title
Change from baseline at end of treatment in Serum intact procollagen type I N terminal propeptide (PINP)
Description
PINP is a biomarker of bone formation.
Time Frame
Up to Day 169
Title
Change from Baseline at End of Treatment in Serum C-terminal type I collagen telopeptide (CTX)
Description
CTX is a bone resorption biomarker.
Time Frame
Up to Day 169
Title
Change from Baseline at End of Treatment in Serum tartrate-resistant acid phosphatase isoform-5b (Tracp-5b)
Description
Tracp-5b is a bone resorption biomarker.
Time Frame
Up to Day 169
Secondary Outcome Measure Information:
Title
Change from Baseline at End of Treatment in Hip Bone Mineral Density
Time Frame
Up to Day 169
Title
Change from Baseline at End of Treatment in Lumbar Spine Bone Mineral Density
Time Frame
Up to Day 169
Title
Summary of Investigator's Bone Lesion Assessment Based on Skeletal X-rays During Follow-up
Time Frame
Up to Day 169
Title
Change from Baseline to End of Treatment in Participant-reported Bone Pain Assessment Using a Visual Analog Scale (VAS) Score
Time Frame
Up to Day 169
Title
Participants with Skeletal-related Adverse Events
Time Frame
Up to Day 169
Title
Pharmacokinetics - AUC
Description
Area under the plasma concentration-time curve
Time Frame
Up to Day 169
Title
Pharmacokinetics - Cmax
Description
Maximum observed concentration
Time Frame
Up to 169 days
Title
Pharmacokinetics - Tmax
Description
Time to maximum observed concentration
Time Frame
Up to 169 days
Title
Pharmacokinetics - t½
Description
Elimination half-life
Time Frame
Up to 169 days
Title
Pharmacokinetics - λz
Description
Elimination rate constant
Time Frame
Up to 169 days
Title
Pharmacokinetics - Vz/F
Description
Volume of distribution
Time Frame
Up to 169 days
Title
Pharmacokinetics - CL/F
Description
Total clearance
Time Frame
Up to 169 days
Title
Pharmacokinetics - Ka
Description
Absorption rate constant
Time Frame
Up to 169 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abderrahmane Laadem, MD
Organizational Affiliation
Celgene Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Investigative Site
City
Moscow
Country
Russian Federation
Facility Name
Investigative Site
City
Saint-Petersburg
Country
Russian Federation
12. IPD Sharing Statement
Citations:
PubMed Identifier
24650009
Citation
Abdulkadyrov KM, Salogub GN, Khuazheva NK, Sherman ML, Laadem A, Barger R, Knight R, Srinivasan S, Terpos E. Sotatercept in patients with osteolytic lesions of multiple myeloma. Br J Haematol. 2014 Jun;165(6):814-23. doi: 10.1111/bjh.12835. Epub 2014 Mar 21.
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A Safety, Tolerability and Efficacy Study of ACE-011 in Patients With Osteolytic Lesions of Multiple Myeloma
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