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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00747123
First received: September 3, 2008
Last updated: September 11, 2012
Last verified: September 2012
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014