Trial Outcomes & Findings for Safety and Efficiency of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis (NCT NCT03164928)

Last Updated: 2024-07-19

Results Overview

Lumbar spine BMD was assessed by DXA and analyzed by analysis of covariance (ANCOVA) including treatment (denosumab vs placebo), baseline age, and baseline BMD z-score. DXA results were converted to z-scores, indicating number of standard deviations from the reference population's mean, with 0 denoting the mean. Positive changes from baseline signify lumbar spine BMD improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

24 participants

Primary outcome timeframe

Baseline and 12 Months

Results posted on

2024-07-19

Participant Flow

This study was conducted at 12 center(s) in Australia, Canada, Columbia, India, Peru, Russia, Turkey, Ukraine, and the United States between May 2018 and December 2023.

Participants were randomized in a 2:1 allocation ratio to receive either denosumab or placebo respectively, in a double-blind manner during the 12-month placebo-controlled double-blind Treatment Period. This was followed by a 12-month denosumab Open-label Treatment Period and a 12-month Off-treatment Observation Period.

Participant milestones

Participant milestones
Measure	Denosumab/Denosumab Participants received 1 mg/kg Denosumab by SC injection up to a maximum of 60 mg, Q6M for 24 months during the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Placebo/Denosumab Participants received matching placebo by SC injection Q6M for the first 12 months of the Treatment Period. This was followed by 1 mg/kg Denosumab administered by SC injection, up to a maximum of 60 mg, Q6M for the second 12 months of the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.
Overall Study STARTED	16	8
Overall Study COMPLETED	15	8
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Denosumab/Denosumab Participants received 1 mg/kg Denosumab by SC injection up to a maximum of 60 mg, Q6M for 24 months during the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Placebo/Denosumab Participants received matching placebo by SC injection Q6M for the first 12 months of the Treatment Period. This was followed by 1 mg/kg Denosumab administered by SC injection, up to a maximum of 60 mg, Q6M for the second 12 months of the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Only participants with available data have been included.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Denosumab/Denosumab n=16 Participants Participants received 1 mg/kg Denosumab by SC injection up to a maximum of 60 mg, Q6M for 24 months during the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Placebo/Denosumab n=8 Participants Participants received matching placebo by SC injection Q6M for the first 12 months of the Treatment Period. This was followed by 1 mg/kg Denosumab administered by SC injection, up to a maximum of 60 mg, Q6M for the second 12 months of the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Total n=24 Participants Total of all reporting groups
Age, Continuous	13.8 Years STANDARD_DEVIATION 2.3 • n=16 Participants	12.8 Years STANDARD_DEVIATION 2.1 • n=8 Participants	13.4 Years STANDARD_DEVIATION 2.2 • n=24 Participants
Sex: Female, Male Female	6 Participants n=16 Participants	4 Participants n=8 Participants	10 Participants n=24 Participants
Sex: Female, Male Male	10 Participants n=16 Participants	4 Participants n=8 Participants	14 Participants n=24 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=16 Participants	3 Participants n=8 Participants	4 Participants n=24 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=16 Participants	5 Participants n=8 Participants	20 Participants n=24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=16 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=16 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Asian	3 Participants n=16 Participants	0 Participants n=8 Participants	3 Participants n=24 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=16 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	0 Participants n=16 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) White	13 Participants n=16 Participants	5 Participants n=8 Participants	18 Participants n=24 Participants
Race (NIH/OMB) More than one race	0 Participants n=16 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=16 Participants	3 Participants n=8 Participants	3 Participants n=24 Participants
Bone Mineral Density (BMD) Z-score at Baseline Lumbar Spine	-1.95 Z-score STANDARD_DEVIATION 1.03 • n=16 Participants • Only participants with available data have been included.	-3.60 Z-score STANDARD_DEVIATION 1.77 • n=8 Participants • Only participants with available data have been included.	-2.50 Z-score STANDARD_DEVIATION 1.51 • n=24 Participants • Only participants with available data have been included.
Bone Mineral Density (BMD) Z-score at Baseline Total Hip	-3.14 Z-score STANDARD_DEVIATION 1.70 • n=16 Participants • Only participants with available data have been included.	-4.56 Z-score STANDARD_DEVIATION 2.08 • n=7 Participants • Only participants with available data have been included.	-3.58 Z-score STANDARD_DEVIATION 1.90 • n=23 Participants • Only participants with available data have been included.
Bone Mineral Density (BMD) Z-score at Baseline Femoral Neck	-3.35 Z-score STANDARD_DEVIATION 1.91 • n=16 Participants • Only participants with available data have been included.	-4.78 Z-score STANDARD_DEVIATION 2.80 • n=7 Participants • Only participants with available data have been included.	-3.79 Z-score STANDARD_DEVIATION 2.25 • n=23 Participants • Only participants with available data have been included.

PRIMARY outcome

Timeframe: Baseline and 12 Months

Population: Primary DXA Analysis Set: all participants in the FAS with baseline and ≥ 1 postbaseline valid DXA assessment of lumbar spine provided by the central imaging vendor during the first 12 months.

Outcome measures

Outcome measures
Measure	Denosumab/Denosumab n=15 Participants Participants received 1 mg/kg Denosumab by SC injection up to a maximum of 60 mg, Q6M for 24 months during the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Placebo/Denosumab n=8 Participants Participants received matching placebo by SC injection Q6M for the first 12 months of the Treatment Period. This was followed by 1 mg/kg Denosumab administered by SC injection, up to a maximum of 60 mg, Q6M for the second 12 months of the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.
Change From Baseline in Lumbar Spine BMD Z-score as Assessed by Dual-energy X-ray Absorptiometry (DXA) at 12 Months	0.23 Z-score Interval -0.054 to 0.506	0.11 Z-score Interval -0.304 to 0.532

SECONDARY outcome

Timeframe: Baseline and 6, 18, 24, and 36 Months

Population: DXA Analysis Set: all participants in the FAS with baseline and ≥ 1 postbaseline valid DXA assessment for lumbar spine as provided by the central imaging vendor. All participants included in the Overall Number of Participants Analyzed contributed data to this outcome measure.

Lumbar spine BMD was assessed by DXA and analyzed by repeated measures analysis with randomization group, visit, baseline age, and baseline BMD z-score as fixed effects. Treatment-by-visit was included as an interaction term. DXA results were converted to z-scores, indicating number of standard deviations from the reference population's mean, with 0 denoting the mean. Positive changes from baseline signify lumbar spine BMD improvement.

Outcome measures

Outcome measures
Measure	Denosumab/Denosumab n=15 Participants Participants received 1 mg/kg Denosumab by SC injection up to a maximum of 60 mg, Q6M for 24 months during the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Placebo/Denosumab n=8 Participants Participants received matching placebo by SC injection Q6M for the first 12 months of the Treatment Period. This was followed by 1 mg/kg Denosumab administered by SC injection, up to a maximum of 60 mg, Q6M for the second 12 months of the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.
Change From Baseline in Lumbar Spine BMD Z-score as Assessed by DXA at 6, 18, 24, and 36 Months Month 24	0.37 Z-score Interval -0.017 to 0.755	0.26 Z-score Interval -0.285 to 0.801
Change From Baseline in Lumbar Spine BMD Z-score as Assessed by DXA at 6, 18, 24, and 36 Months Month 36	-0.23 Z-score Interval -0.833 to 0.372	0.57 Z-score Interval -0.268 to 1.416
Change From Baseline in Lumbar Spine BMD Z-score as Assessed by DXA at 6, 18, 24, and 36 Months Month 6	0.28 Z-score Interval 0.095 to 0.468	0.11 Z-score Interval -0.176 to 0.391
Change From Baseline in Lumbar Spine BMD Z-score as Assessed by DXA at 6, 18, 24, and 36 Months Month 18	0.32 Z-score Interval -0.034 to 0.679	0.30 Z-score Interval -0.206 to 0.8

SECONDARY outcome

Timeframe: Baseline and 6, 12, 18, 24, and 36 Months

Population: DXA Analysis Set: all participants in the FAS with baseline and ≥ 1 postbaseline valid DXA assessment for total hip and femoral neck as provided by the central imaging vendor.

Proximal femur (total hip and femoral neck) BMD was assessed by DXA and analyzed by repeated measures analysis with randomization group, visit, baseline age, and baseline BMD z-score as fixed effects. Treatment-by-visit was included as an interaction term. DXA results were converted to z-scores, indicating number of standard deviations from the reference population's mean, with 0 denoting the mean. Positive changes from baseline signify proximal femur BMD improvement.

Outcome measures

Outcome measures
Measure	Denosumab/Denosumab n=15 Participants Participants received 1 mg/kg Denosumab by SC injection up to a maximum of 60 mg, Q6M for 24 months during the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Placebo/Denosumab n=7 Participants Participants received matching placebo by SC injection Q6M for the first 12 months of the Treatment Period. This was followed by 1 mg/kg Denosumab administered by SC injection, up to a maximum of 60 mg, Q6M for the second 12 months of the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 18 (Total Hip)	0.48 Z-score Interval 0.015 to 0.937	0.75 Z-score Interval 0.061 to 1.434
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 36 (Total Hip)	0.64 Z-score Interval -0.149 to 1.436	0.73 Z-score Interval -0.384 to 1.85
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 24 (Femoral Neck)	0.75 Z-score Interval 0.0 to 1.495	0.64 Z-score Interval -0.449 to 1.724
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 6 (Total Hip)	0.22 Z-score Interval -0.103 to 0.552	0.64 Z-score Interval 0.104 to 1.171
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 12 (Total Hip)	0.24 Z-score Interval -0.079 to 0.554	0.30 Z-score Interval -0.168 to 0.759
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 24 (Total Hip)	0.52 Z-score Interval 0.0 to 1.033	0.69 Z-score Interval -0.062 to 1.447
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 6 (Femoral Neck)	0.42 Z-score Interval 0.0 to 0.849	0.60 Z-score Interval -0.037 to 1.241
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 12 (Femoral Neck)	0.53 Z-score Interval 0.029 to 1.03	0.43 Z-score Interval -0.294 to 1.161
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 18 (Femoral Neck)	0.85 Z-score Interval 0.261 to 1.446	0.48 Z-score Interval -0.387 to 1.35
Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months Month 36 (Femoral Neck)	1.00 Z-score Interval -0.008 to 2.012	0.63 Z-score Interval -0.798 to 2.05

SECONDARY outcome

Timeframe: Month 12, 24, and 36

Population: FAS: all participants randomized into the study.

Number of participants who have at least one long bone fracture or vertebral fracture, and number of participants who have more than one long bone fracture or vertebral fracture.

Outcome measures

Outcome measures
Measure	Denosumab/Denosumab n=16 Participants Participants received 1 mg/kg Denosumab by SC injection up to a maximum of 60 mg, Q6M for 24 months during the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Placebo/Denosumab n=8 Participants Participants received matching placebo by SC injection Q6M for the first 12 months of the Treatment Period. This was followed by 1 mg/kg Denosumab administered by SC injection, up to a maximum of 60 mg, Q6M for the second 12 months of the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.
Number of Participants With X-ray Confirmed Long-bone Fractures and/or Vertebral Fractures at 12, 24, and 36 Months Month 12 (more than 1 fracture)	2 Participants	1 Participants
Number of Participants With X-ray Confirmed Long-bone Fractures and/or Vertebral Fractures at 12, 24, and 36 Months Month 24 (more than 1 fracture)	2 Participants	0 Participants
Number of Participants With X-ray Confirmed Long-bone Fractures and/or Vertebral Fractures at 12, 24, and 36 Months Month 36 (more than 1 fracture)	3 Participants	1 Participants
Number of Participants With X-ray Confirmed Long-bone Fractures and/or Vertebral Fractures at 12, 24, and 36 Months Month 12 (at least 1 fracture)	2 Participants	2 Participants
Number of Participants With X-ray Confirmed Long-bone Fractures and/or Vertebral Fractures at 12, 24, and 36 Months Month 24 (at least 1 fracture)	3 Participants	3 Participants
Number of Participants With X-ray Confirmed Long-bone Fractures and/or Vertebral Fractures at 12, 24, and 36 Months Month 36 (at least 1 fracture)	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Month 12, 24, and 36

Population: Vertebral Fracture Analysis Set: all participants in the FAS who have a non-missing baseline and ≥ 1 non-missing postbaseline X-ray vertebral evaluation as provided by the central imaging vendor, on or before the time point under consideration.

Number of participants with improving vertebral fractures. An improving fracture is defined as one showing signs of healing/repair from baseline as assessed by X-ray.

Outcome measures

Outcome measures
Measure	Denosumab/Denosumab n=15 Participants Participants received 1 mg/kg Denosumab by SC injection up to a maximum of 60 mg, Q6M for 24 months during the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Placebo/Denosumab n=7 Participants Participants received matching placebo by SC injection Q6M for the first 12 months of the Treatment Period. This was followed by 1 mg/kg Denosumab administered by SC injection, up to a maximum of 60 mg, Q6M for the second 12 months of the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.
Number of Participants With Improving Vertebral Fractures at 12, 24, and 36 Months Month 12	3 Participants	1 Participants
Number of Participants With Improving Vertebral Fractures at 12, 24, and 36 Months Month 24	2 Participants	1 Participants
Number of Participants With Improving Vertebral Fractures at 12, 24, and 36 Months Month 36	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Month 12, 24, and 36

Population: FAS: all participants randomized into the study.

Number of participants who have at least one vertebral fracture or non-vertebral fracture, and number of participants who have more than one vertebral fracture or non-vertebral fracture.

Outcome measures

Outcome measures
Measure	Denosumab/Denosumab n=16 Participants Participants received 1 mg/kg Denosumab by SC injection up to a maximum of 60 mg, Q6M for 24 months during the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.	Placebo/Denosumab n=8 Participants Participants received matching placebo by SC injection Q6M for the first 12 months of the Treatment Period. This was followed by 1 mg/kg Denosumab administered by SC injection, up to a maximum of 60 mg, Q6M for the second 12 months of the Treatment Period. Participants were then followed for an additional 12 months during the Off-treatment Observation Period.
Number of Participants With New and Worsening Vertebral and Non-vertebral Fractures at 12, 24, and 36 Months Month 12 (at least 1 fracture)	2 Participants	2 Participants
Number of Participants With New and Worsening Vertebral and Non-vertebral Fractures at 12, 24, and 36 Months Month 24 (at least 1 fracture)	3 Participants	3 Participants
Number of Participants With New and Worsening Vertebral and Non-vertebral Fractures at 12, 24, and 36 Months Month 36 (more than 1 fracture)	3 Participants	1 Participants
Number of Participants With New and Worsening Vertebral and Non-vertebral Fractures at 12, 24, and 36 Months Month 36 (at least 1 fracture)	3 Participants	3 Participants
Number of Participants With New and Worsening Vertebral and Non-vertebral Fractures at 12, 24, and 36 Months Month 12 (more than 1 fracture)	2 Participants	1 Participants
Number of Participants With New and Worsening Vertebral and Non-vertebral Fractures at 12, 24, and 36 Months Month 24 (more than 1 fracture)	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and month 12, 24, and 36

Population: Patient Reported Outcomes (PRO) Analysis Set: all participants in the FAS with baseline and at least one valid CHQ-PF-50 response at post-baseline. All participants included in the Overall Number of Participants Analyzed contributed data to this outcome measure.

The CHQ-PF-50 is a 50-item questionnaire to be completed by the parents or guardians of children between 5 and 18 years of age. The physical summary score ranges from 0-100 with higher scores indicating better physical health.