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

Phase 2

Completed

Conditions: Multiple Myeloma

Interventions: Biological: ACE-011
Biological: Placebo

Registration Number: NCT00747123

Lead Sponsor: Celgene

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACE-011 0.1 mg/kg	ACE-011	Subcutaneous injection of ACE-011 0.1 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).
ACE-011 0.3 mg/kg	ACE-011	Subcutaneous injection of ACE-011 0.3 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).
ACE-011 0.5 mg/kg	ACE-011	Subcutaneous injection of ACE-011 0.5 mg/kg every 28 days totaling four doses (days 1, 29, 57 and 85).
Placebo	Placebo	Subcutaneous injection on days 1, 29, 57 and 85.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	From first dose to termination visit on Day 169	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.
Number of Participants With Serious Adverse Events (SAEs)	From first dose up to termination visit on Day 169	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.
Change From Baseline in Hemoglobin	Day 1 (baseline), Day 8, Day 29, Day 36, Day 57, Day 85, Day 113, Day 169	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug	From first dose to termination visit on Day 169	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.
Number of Participants With Electrocardiogram Abnormalities	Pre-dose, Day 1, Day 92, and Day 169	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.
Number of Participants With Hypertension or Increased Blood Pressure	From baseline up to Day 92	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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Skeletal-related Events (SRE)	From first dose up to 2 weeks post first dose	Skeletal-related events are defined as pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression, within 2 weeks of study enrollment. They are determined by skeletal surveys, including x-rays of the skull, entire spine, pelvis, ribs, humeri, and femora.
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	The visual analog scale (VAS) is a pain rating scale. Scores are based on the percent change from baseline (Day 1) in self-reported measures of symptoms that are recorded with a single handwritten mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale-"no pain" on the left end (0 cm) of the scale and the "worst pain" on the right end of the scale (10 cm). Measurements from the starting point (left end) of the scale to the patients' marks are recorded in centimeters and are interpreted as their pain. The values can be used to track pain progression for a patient or to compare pain between patients with similar conditions. In addition to pain, the scale has also been used to evaluate mood, appetite, asthma, dyspepsia, and ambulation.