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

Purpose

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

Condition	Intervention	Phase
Multiple Myeloma	Biological: ACE-011 Biological: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Multiple Myeloma

U.S. FDA Resources

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:

Participants with Treatment-emergent Adverse Experiences [ Time Frame: Up to Day 169 ] [ Designated as safety issue: Yes ]
Change from baseline at end of treatment in Bone Specific Alkaline Phosphatase (BSAP) [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
BSAP is a biomarker of bone formation.
Change from baseline at end of treatment in Serum intact procollagen type I N terminal propeptide (PINP) [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
PINP is a biomarker of bone formation.
Change from Baseline at End of Treatment in Serum C-terminal type I collagen telopeptide (CTX) [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
CTX is a bone resorption biomarker.
Change from Baseline at End of Treatment in Serum tartrate-resistant acid phosphatase isoform-5b (Tracp-5b) [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
Tracp-5b is a bone resorption biomarker.

Secondary Outcome Measures:

Change from Baseline at End of Treatment in Hip Bone Mineral Density [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
Change from Baseline at End of Treatment in Lumbar Spine Bone Mineral Density [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
Summary of Investigator's Bone Lesion Assessment Based on Skeletal X-rays During Follow-up [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Participants with Skeletal-related Adverse Events [ Time Frame: Up to Day 169 ] [ Designated as safety issue: Yes ]
Pharmacokinetics - AUC [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
Area under the plasma concentration-time curve
Pharmacokinetics - Cmax [ Time Frame: Up to 169 days ] [ Designated as safety issue: No ]
Maximum observed concentration
Pharmacokinetics - Tmax [ Time Frame: Up to 169 days ] [ Designated as safety issue: No ]
Time to maximum observed concentration
Pharmacokinetics - t½ [ Time Frame: Up to 169 days ] [ Designated as safety issue: No ]
Elimination half-life
Pharmacokinetics - λz [ Time Frame: Up to 169 days ] [ Designated as safety issue: No ]
Elimination rate constant
Pharmacokinetics - Vz/F [ Time Frame: Up to 169 days ] [ Designated as safety issue: No ]
Volume of distribution
Pharmacokinetics - CL/F [ Time Frame: Up to 169 days ] [ Designated as safety issue: No ]
Total clearance
Pharmacokinetics - Ka [ Time Frame: Up to 169 days ] [ Designated as safety issue: No ]
Absorption rate constant

Enrollment:	30
Study Start Date:	September 2008
Study Completion Date:	August 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Subcutaneous injection on days 1, 29, 57 and 85.	Biological: Placebo Placebo given by the subcutaneous route of administration monthly for 4 doses.
Experimental: ACE-011 0.1 mg/kg Subcutaneous injection of ACE-011 0.1 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).	Biological: ACE-011 ACE-011 given by the subcutaneous route of administration monthly for 4 doses. Other Name: hActRIIA-IgG1
Experimental: ACE-011 0.3 mg/kg Subcutaneous injection of ACE-011 0.3 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).	Biological: ACE-011 ACE-011 given by the subcutaneous route of administration monthly for 4 doses. Other Name: hActRIIA-IgG1
Experimental: ACE-011 0.5 mg/kg Subcutaneous injection of ACE-011 0.5 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).	Biological: ACE-011 ACE-011 given by the subcutaneous route of administration monthly for 4 doses. Other Name: hActRIIA-IgG1

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00747123

Locations

Russian Federation
Investigative Site
Moscow, Russian Federation
Investigative Site
Saint-Petersburg, Russian Federation

Sponsors and Collaborators

Celgene Corporation

Investigators

Study Director:

Abderrahmane Laadem, MD

Celgene Corporation

More Information

No publications provided

Responsible Party:	Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00747123 History of Changes
Other Study ID Numbers:	A011-04
Study First Received:	September 3, 2008
Last Updated:	September 11, 2012
Health Authority:	Russia: Ministry of Health of the Russian Federation

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 19, 2013