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

NCT00747123 | Completed Phase 2 Results DMC

• 1 other identifier: A011-04
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  A treatment emergent adverse event (TEAE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causality assessment. A TEAE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Any worsening (i.e., any clinical significant adverse change in frequency and/or intensity) of a preexisting condition, which was temporally associated with the use of the sponsor's medicinal (investigational) product, was also a TEAE. The number of participants with at least one TEAE are reported.

  From first dose to termination visit on Day 169

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug

  A treatment emergent adverse event (TEAE) related to study drug was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, that was determined to be related to the study drug. A TEAE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. Any worsening (i.e., any clinical significant adverse change in frequency and/or intensity) of a preexisting condition, which was temporally associated with the use of the sponsor's medicinal (investigational) product, was also a TEAE. The number of participants with at least one TEAE are reported. Treatment emergent adverse events were assessed by the investigator as possibly, probably, or definitely related to the study drug.

  From first dose to termination visit on Day 169

• Number of Participants With Serious Adverse Events (SAEs)

  A Serious Adverse Event (SAE) was defined as any untoward medical occurrence that at any dose (including overdose) that was fatal, was life threatening, required or prolonged inpatient hospitalization, resulted in permanent or significant disability/incapacity, or was a congenital anomaly/birth defect. The number of participants with at least one serious adverse event are reported.

  From first dose up to termination visit on Day 169

• Change From Baseline in Hemoglobin

  Summary of the change from baseline in hemoglobin (g/dL) by the pre-specified timepoints. Baseline was defined as the last measurement prior to dosing. Data were summarized for all treated participants who had at least 1 postdosing measurement.

  Day 1 (baseline), Day 8, Day 29, Day 36, Day 57, Day 85, Day 113, Day 169

• Number of Participants With Electrocardiogram Abnormalities

  The number of participants with at least one clinically significant postbaseline electrocardiogram abnormality. The abnormalities included left ventricular hypertrophy, atrial fibrillation, sinus bradycardia, sinus tachycardia, and myocardial ischemia. Data is reported as the cumulative number of participants with abnormalities over the scheduled collection timepoints.

  Pre-dose, Day 1, Day 92, and Day 169

• Number of Participants With Hypertension or Increased Blood Pressure

  The number of participants who experienced hypertension or an increase in blood pressure from baseline up to Day 92. Abnormal blood pressure was defined as: * Systolic blood pressure ≤ 90 or ≥ 180 mmHg * Systolic blood pressure change (increase or decrease) ≥ 20 mmHg * Diastolic blood pressure ≤ 60 or ≥ 100 mmHg * Diastolic blood pressure change (increase or decrease) ≥ 15 mmHg

  From baseline up to Day 92

Secondary Outcomes (2)

• Number of Participants With Skeletal-related Events (SRE)

  From first dose up to 2 weeks post first dose

• Percent Change From Baseline in Bone Pain Visual Analog Scale (VAS)

  From baseline (Day 1) to Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Subcutaneous injection on days 1, 29, 57 and 85.

Biological: Placebo

ACE-011 0.1 mg/kg

EXPERIMENTAL

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 0.3 mg/kg

EXPERIMENTAL

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 0.5 mg/kg

EXPERIMENTAL

Subcutaneous injection of ACE-011 0.5 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).

Biological: ACE-011

Interventions

ACE-011 BIOLOGICAL

ACE-011 given by the subcutaneous route of administration monthly for 4 doses.

Also known as: hActRIIA-IgG1

ACE-011 0.1 mg/kg; ACE-011 0.3 mg/kg; ACE-011 0.5 mg/kg

Placebo BIOLOGICAL

Placebo given by the subcutaneous route of administration monthly for 4 doses.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Celgene: lead

Study Sites (2)

Investigative Site

Moscow, Russia

Location

Investigative Site

Saint Petersburg, Russia

Location

Related Publications (1)

• 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.

  PMID: 24650009 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ACE-011

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Abderrahmane Laadem, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2008
• First Posted: September 4, 2008
• Study Start: September 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: October 3, 2024
• Results First Posted: October 3, 2024

Record last verified: 2024-06

Locations

RU (2)