Trial Outcomes & Findings for A Safety, Tolerability and Efficacy Study of ACE-011 in Patients With Osteolytic Lesions of Multiple Myeloma (NCT NCT00747123)

NCT ID: NCT00747123

Last Updated: 2024-10-03

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: From first dose to termination visit on Day 169
• Results posted on: 2024-10-03

Participant Flow

Participant milestones

Measure	Placebo Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Overall Study STARTED	6	8	8	8
Overall Study COMPLETED	6	6	7	7
Overall Study NOT COMPLETED	0	2	1	1

Reasons for withdrawal

Measure	Placebo Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Overall Study Investigator's request	0	0	1	0
Overall Study Withdrew consent	0	1	0	0
Overall Study Adverse Event	0	1	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=6 Participants Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 n=8 Participants 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 n=8 Participants 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 n=8 Participants 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	Total n=30 Participants Total of all reporting groups
Age, Continuous	62.0 Years STANDARD_DEVIATION 7.92 • n=5 Participants	60.5 Years STANDARD_DEVIATION 13.28 • n=7 Participants	63.6 Years STANDARD_DEVIATION 7.50 • n=5 Participants	57.8 Years STANDARD_DEVIATION 12.30 • n=4 Participants	60.9 Years STANDARD_DEVIATION 10.42 • n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	8 Participants n=4 Participants	29 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: From first dose to termination visit on Day 169

Population: All randomized participants

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.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 n=8 Participants 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 n=8 Participants 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 n=8 Participants 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	4 Participants	7 Participants	7 Participants	8 Participants

PRIMARY outcome

Timeframe: From first dose to termination visit on Day 169

Population: All randomized participants

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.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 n=8 Participants 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 n=8 Participants 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 n=8 Participants 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug	0 Participants	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: From first dose up to termination visit on Day 169

Population: All randomized participants

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.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 n=8 Participants 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 n=8 Participants 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 n=8 Participants 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Number of Participants With Serious Adverse Events (SAEs)	0 Participants	1 Participants	0 Participants	3 Participants

PRIMARY outcome

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

Population: All randomized participants

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.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 n=8 Participants 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 n=8 Participants 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 n=8 Participants 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Change From Baseline in Hemoglobin Day 8	0.47 g/dL Standard Deviation 0.288	0.89 g/dL Standard Deviation 1.254	0.83 g/dL Standard Deviation 0.599	0.80 g/dL Standard Deviation 0.844
Change From Baseline in Hemoglobin Day 29	0.50 g/dL Standard Deviation 0.607	-0.91 g/dL Standard Deviation 1.844	0.66 g/dL Standard Deviation 0.457	0.96 g/dL Standard Deviation 1.648
Change From Baseline in Hemoglobin Day 36	1.02 g/dL Standard Deviation 0.643	0.73 g/dL Standard Deviation 1.873	1.00 g/dL Standard Deviation 0.787	1.48 g/dL Standard Deviation 1.167
Change From Baseline in Hemoglobin Day 57	0.53 g/dL Standard Deviation 0.602	0.47 g/dL Standard Deviation 1.682	1.09 g/dL Standard Deviation 1.022	1.00 g/dL Standard Deviation 1.22
Change From Baseline in Hemoglobin Day 85	0.78 g/dL Standard Deviation 0.958	0.57 g/dL Standard Deviation 0.907	0.86 g/dL Standard Deviation 1.323	1.56 g/dL Standard Deviation 0.704
Change From Baseline in Hemoglobin Day 113	0.33 g/dL Standard Deviation 0.789	0.53 g/dL Standard Deviation 1.141	0.96 g/dL Standard Deviation 1.620	0.97 g/dL Standard Deviation 1.024
Change From Baseline in Hemoglobin Day 169/Early Termination	0.13 g/dL Standard Deviation 1.140	0.57 g/dL Standard Deviation 1.500	0.33 g/dL Standard Deviation 1.763	0.03 g/dL Standard Deviation 2.392

PRIMARY outcome

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

Population: All randomized participants

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.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 n=8 Participants 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 n=8 Participants 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 n=8 Participants 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Number of Participants With Electrocardiogram Abnormalities	4 Participants	2 Participants	2 Participants	2 Participants

PRIMARY outcome

Timeframe: From baseline up to Day 92

Population: All randomized participants

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

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 n=8 Participants 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 n=8 Participants 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 n=8 Participants 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Number of Participants With Hypertension or Increased Blood Pressure	0 Participants	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From first dose up to 2 weeks post first dose

Population: All randomized participants

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.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 n=8 Participants 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 n=8 Participants 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 n=8 Participants 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Number of Participants With Skeletal-related Events (SRE)	0 Participants	1 Participants	2 Participants	2 Participants

SECONDARY outcome

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

Population: All treated participants who had at least 1 postdosing measurement

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.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.	0.1 mg/kg ACE 011 n=8 Participants 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	0.3 mg/kg ACE 011 n=8 Participants 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	0.5 mg/kg ACE 011 n=7 Participants 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).
Percent Change From Baseline in Bone Pain Visual Analog Scale (VAS) Day 29	-6.0 Percent change Standard Deviation 12.25	-9.4 Percent change Standard Deviation 22.60	-5.8 Percent change Standard Deviation 25.03	-6.4 Percent change Standard Deviation 23.87
Percent Change From Baseline in Bone Pain Visual Analog Scale (VAS) Day 57	-7.2 Percent change Standard Deviation 6.77	-8.0 Percent change Standard Deviation 26.09	-11.0 Percent change Standard Deviation 33.87	-11.6 Percent change Standard Deviation 26.34
Percent Change From Baseline in Bone Pain Visual Analog Scale (VAS) Day 85	-4.5 Percent change Standard Deviation 3.78	-12.7 Percent change Standard Deviation 23.08	-10.5 Percent change Standard Deviation 37.50	-11.1 Percent change Standard Deviation 28.79
Percent Change From Baseline in Bone Pain Visual Analog Scale (VAS) Day 113	-3.5 Percent change Standard Deviation 4.46	-13.7 Percent change Standard Deviation 25.03	-12.3 Percent change Standard Deviation 38.04	-11.4 Percent change Standard Deviation 29.43
Percent Change From Baseline in Bone Pain Visual Analog Scale (VAS) Day 141	0.7 Percent change Standard Deviation 13.05	-13.7 Percent change Standard Deviation 25.26	-15.0 Percent change Standard Deviation 37.33	-12.1 Percent change Standard Deviation 32.79
Percent Change From Baseline in Bone Pain Visual Analog Scale (VAS) Day 169	-3.0 Percent change Standard Deviation 7.59	-14.7 Percent change Standard Deviation 24.59	-15.0 Percent change Standard Deviation 38.40	-13.6 Percent change Standard Deviation 30.36

Adverse Events

ACE 011 0.1 mg/kg

Serious events: 1 serious events

Other events: 7 other events

Deaths: 1 deaths

ACE 011 0.3 mg/kg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

ACE 011 0.5 mg/kg

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	ACE 011 0.1 mg/kg n=8 participants at risk 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	ACE 011 0.3 mg/kg n=8 participants at risk 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	ACE 011 0.5 mg/kg n=8 participants at risk 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	Placebo n=6 participants at risk Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.
Cardiac disorders Atrial fibrillation	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
General disorders Sudden death	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Infections and infestations Pneumonia	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.

Other adverse events

Measure	ACE 011 0.1 mg/kg n=8 participants at risk 0.1 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	ACE 011 0.3 mg/kg n=8 participants at risk 0.3 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169)	ACE 011 0.5 mg/kg n=8 participants at risk 0.5 mg/kg administered via subcutaneous injection every 28 days for a total of four doses (i.e., Days 1, 29, 57, and 85), with safety follow-up visits 1 week after each dose (i.e., Days 8, 36, 64, and 92). After completion of the treatment period, participants returned to the study site monthly for follow-up assessments for an additional 3 months (i.e., Days 113, 141, and 169).	Placebo n=6 participants at risk Placebo was administered within 28 days of screening. Subsequent doses were administered every 28 days for a total of four doses.
Blood and lymphatic system disorders Anaemia	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	25.0% 2/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Blood and lymphatic system disorders Eosinophilia	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	16.7% 1/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Blood and lymphatic system disorders Granulocytopenia	25.0% 2/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Blood and lymphatic system disorders Leukopenia	37.5% 3/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Blood and lymphatic system disorders Neutropenia	50.0% 4/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	75.0% 6/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	75.0% 6/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	66.7% 4/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Blood and lymphatic system disorders Thrombocytopenia	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	25.0% 2/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Cardiac disorders Angina pectoris	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Cardiac disorders Atrial conduction time prolongation	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Cardiac disorders Atrial fibrillation	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Cardiac disorders Myocardial ischaemia	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	16.7% 1/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Cardiac disorders Sinus bradycardia	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	16.7% 1/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Endocrine disorders Hypothyroidism	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Eye disorders Blepharitis	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Gastrointestinal disorders Constipation	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
General disorders Asthenia	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
General disorders Fatigue	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	16.7% 1/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
General disorders Oedema peripheral	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
General disorders Pyrexia	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Infections and infestations Bronchitis	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	16.7% 1/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Infections and infestations Herpes zoster	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	16.7% 1/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Infections and infestations Pneumonia	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Infections and infestations Respiratory tract infection	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Infections and infestations Rhinitis	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Injury, poisoning and procedural complications Compression fracture	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Injury, poisoning and procedural complications Concussion	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Investigations Blood pressure increased	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Investigations Platelet count decreased	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	16.7% 1/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Musculoskeletal and connective tissue disorders Pathological fracture	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Nervous system disorders Somnolence	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Skin and subcutaneous tissue disorders Hair texture abnormal	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Skin and subcutaneous tissue disorders Rash	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Vascular disorders Hypertension	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Vascular disorders Phlebitis	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.
Vascular disorders Post thrombotic syndrome	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	12.5% 1/8 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.	0.00% 0/6 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 months). SAEs and Other AEs were assessed from first dose to Day 169.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please Email

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER