Osteogenesis Imperfecta
Conditions
Keywords
Amgen, OI, Bone
Brief summary
This is a prospective, multicenter, single-arm study in children 2 to 17 years of age with OI to evaluate efficacy and safety of denosumab.
Detailed description
To evaluate the effect of denosumab in lumbar spine bone mineral density (BMD) Z-score at 12 months, as assessed by dual-energy X-ray absorptiometry (DXA), in children 2 to 17 years of age (at the time of screening) on a 3-Month Dosing Regimen with osteogenesis imperfecta (OI)
Interventions
DRUGDenosumab
Subcutaneous (SC) injection.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
• Eligibility criteria relates to initial enrollment into this study (6-Month Dosing Regimen). Subjects reconsenting to a 3-Month Dosing Regimen will not repeat eligibility assessments Inclusion Criteria: • Clinical diagnosis of OI defined as a clinical history consistent with type I-IV OI Clinical severity of OI as defined by 2 or more prevalent vertebral compression fractures; OR1 prevalent vertebral compression fracture and 1 or more nonvertebral fractures within the previous 2 years; OR 3 or more fractures within the previous 2 years.
Exclusion criteria
* Inability or unwillingness to comply with the requirements for frequent calcium and phosphorus monitoring for 14 days after the first dose of denosumab (only applies to the first 5 subjects age 11 to17 enrolled in the study and the first 5 subjects of any age meeting the criteria for increased bone turnover * Currently unhealed fracture or osteotomy as defined by orthopedic opinion * Osteotomy within 5 months of screening * Evidence of untreated oral cavities or oral infections * Recent or planned invasive dental procedure * Surgical tooth extraction which has not healed by screening * History of an electrophoresis pattern inconsistent with type I to IV OI * History of genetic testing results inconsistent with type I to IV OI * Abnormalities of the following per central laboratory reference ranges at screening: Serum albumin corrected calcium \< lower limit of normal (LLN) Serum vitamin D \< 20 ng/mL; re-screening for Vitamin D level \< 20 ng/mL will be allowed, after adequate supplementation * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \> 1.5 x upper limit of normal (ULN) * Total bilirubin (TBL) \> 1.5 x ULN (subjects with Gilbert syndrome are eligible) * Serum phosphorus \< LLN * Serum alkaline phosphatase \> 20% above the ULN or \> 20% below the LLN * Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 (calculated bythe Schwartz equation at screening) Evidence of any of the following: Current hyperthyroidism (unless well-controlled on stable antithyroid therapy) * Current clinical hypothyroidism (unless well-controlled on stable thyroid replacement therapy) * History of hyperparathyroidism * Current hypoparathyroidism * Current, uncontrolled hypercalcemia (albumin-corrected serum Ca \>10% ULN) * History of osteomalacia or rickets (chart review) * Other bone diseases that affect bone metabolism (eg, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis, hypophosphatasia) * History of autoimmune disease * History of rare hereditary problems of fructose intolerance * Positive blood screen for human immunodeficiency virus -1 or -2 antibody * Positive blood screen for hepatitis B surface antigen or hepatitis C antibody * Received other osteoporosis treatment or bone active treatment with the following guidelines: * Prior treatment with * denosumab * fluoride or strontium for bone disease (fluoride taken for routine dental care is permitted) * parathyroid hormone (PTH) or PTH derivatives within 12 months prior to screening * zoledronic acid within 6 months prior to screening * oral bisphosphonates or intravenous bisphosphonates other than zoledronic acid if the first dose of denosumab would be before their next scheduled bisphosphonate dose would have been given * Administration of systemic glucocorticoids (≥ 5.0 mg prednisone equivalents/day for more than 10 days) within 3 months of screening. * Topical and inhaled glucocorticoids will be allowed * Administration of any of the following treatment within 3 months of screening: * Growth hormone (subjects on stable dose of growth hormone for at least 3 months prior to screening will be allowed) * Currently receiving treatment in another investigational drug study, or less than 30 days since ending treatment on another investigational drugstudy(s), or current or planned participation in a clinical trial that would preclude compliance with study requirements Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score at 12 Months | Baseline and 12 months | Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA) adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months | Baseline, 6 and 12 months | Proximal femur (total hip and femoral neck) BMD Z-score was measured by DXA adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD. |
| Percentage of Participants With at Least 1 X-ray Confirmed Long Bone or New and Worsening Vertebral Fracture | Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months | — |
| Percentage of Participants With at Least 1 X-ray Confirmed New and Worsening Vertebral Fracture | Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months | — |
| Percentage of Participants With at Least 1 X-ray Confirmed New Vertebral Fracture | Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months | — |
| Percentage of Participants Wth at Least 1 X-ray Confirmed Improving Vertebral Fracture | Q3M Dosing Regimen: Baseline up to 12 months | — |
| Percentage of Participants With at Least 1 Vertebral and Nonvertebral Fracture | Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months | — |
| Change From Baseline in Child Health Questionnaire-Parent Form Physical Summary Score (CHQ-PF-50) at 12 Months | Baseline and 12 months | The CHQ-PF-50 was a 50-item questionnaire completed by the parents or guardians of children between 5 and 18 years of age. The 50 questions measure 14 domains which were summarized as the physical and psychological summary scores. Each summary score was transformed and could range from 0 to 100, with higher score indicating better physical and psychosocial health. A negative change from Baseline indicates decreased well-being. |
| Change From Baseline in Lumbar Spine BMD Z-score at 6 Months | Baseline and 6 months | Lumbar spine BMD was measured by DXA adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD. |
| Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index Score at 12 Months | Baseline and 12 months | The disability domain (questions 1-54) of the CHAQ was used to measure the participant's assessment of physical functioning or the parent's assessment of the child's physical functioning. The disability index comprised of 8 categories (dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and activities). Scoring ranged from 1 to 5; 1 was without any difficulty, 2 was with some difficulty, 3 was with much difficulty, and 4 was unable to do. An answer of not applicable was scored as a 5, but was not counted. If a child required assistance from another person or used an aid or other device for any of the 8 categories, the minimum score for that category was recorded as a 3. The CHAQ questions were scored and converted to a total index score ranging from 0 to 3. Negative change from Baseline indicates an improvement. |
| Change From Baseline in Wong-Baker Faces Pain Rating Scale (WBFPRS) at 12 Months | Baseline and 12 months | Participants were asked to report their level of pain by choosing a face that best described their own pain (the corresponding number: 0, 2, 4, 6, 8, 10) were then recorded. The WBFPRS ranged from 0, no hurt, to 10, hurts worst. A negative change from baseline indicates an improvement. |
| Serum Concentration of Denosumab | Days 1 (predose), 10, 30, and 60, & weeks 12, 24, 36, 48, 60, 72 (end of study visit), early termination visit, & follow-up visit 12 weeks after last dose (average duration of treatment: 231 days) | — |
| Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Baseline and Days 10 and 30, and Months 3, 6, 9, 12, 15 and 18 | — |
| BTM - Bone-specific Alkaline Phosphatase (BSAP) | Baseline and Days 10 and 30, and Months 3, 6, 9, 12, and 15 | — |
| Change From Baseline in Growth Velocity at 12 Months | Baseline and 12 months | Change from baseline in growth velocity was determined by calculating age-adjusted Z-scores for height, weight and body mass index (BMI). Height-for-age Z-score was defined as the difference between the participant's height and the median height for the population with the same age and gender, divided by the population standard deviation. The definitions of growth velocity based on weight and BMI were analogously calculated. To programmatically calculate the Z-scores, the National Center for Health Statistics percentiles growth charts, based on the 2000 Center for Disease Control and Prevention (CDC) (http://www.cdc.gov/growthcharts/c c\_charts.htm), and the CDC Anthropometric Software Package 3.0 Z-scores were used. During normal growth, the change in z-score for each of the three should equal 0. A positive change in any of the three indicates growth acceleration, whereas a negative change indicates deceleration. |
| Change From Baseline in CHQ-PF-50 Psychological Summary Score at 12 Months | Baseline and 12 months | The CHQ-PF-50 was a 50-item questionnaire completed by the parents or guardians of children between 5 and 18 years of age. The 50 questions measure 14 domains which were summarized as the physical and psychological summary scores. Each summary score was transformed and could range from 0 to 100, with higher score indicating better physical and psychosocial health. A positive change from Baseline indicates improved well-being. |
Countries
Australia, Belgium, Bulgaria, Canada, Czechia, France, Germany, Hungary, Italy, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 32 centers in North America, Europe, and Australia from June 2015 to March 2022.
Participants by arm
| Arm | Count |
|---|---|
| Denosumab Participants received denosumab 1 mg/kg (up to a maximum of 60 mg) subcutaneously every 6 months (Q6M) for up to 36 months.
Participants were dose adjusted from Q6M to every 3 months (Q3M) after early efficacy and PK data were analyzed. Participants enrolled and still receiving denosumab were transitioned from Q6M to Q3M dosing schedule. Participants could transition to Q3M dosing schedule up to and including the date they attended for their Month 36 visit under the Q6M dosing regimen. Those participants received denosumab during the Q3M dosing regimen for 12 months. Participants who transitioned to Q3M at month 18 of the Q6M dosing regimen received denosumab Q3M for up to 18 months. | 153 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 3-Month Dosing Period | Decision by sponsor | 14 |
| 3-Month Dosing Period | Withdrawal by Subject | 6 |
| 6-Month Dosing Period | Decision by sponsor | 2 |
| 6-Month Dosing Period | Lost to Follow-up | 2 |
| 6-Month Dosing Period | Transitioning to Q3M | 60 |
| 6-Month Dosing Period | Withdrawal by Subject | 34 |
Baseline characteristics
| Characteristic | Denosumab |
|---|---|
| Age, Continuous | 9.3 Years STANDARD_DEVIATION 3.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Multiple | 4 Participants |
| Race/Ethnicity, Customized Other | 8 Participants |
| Race/Ethnicity, Customized White | 135 Participants |
| Sex: Female, Male Female | 73 Participants |
| Sex: Female, Male Male | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 153 | 0 / 60 |
| other Total, other adverse events | 141 / 153 | 38 / 60 |
| serious Total, serious adverse events | 52 / 153 | 12 / 60 |
Outcome results
Primary
Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score at 12 Months
Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA) adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD.
Time frame: Baseline and 12 months
Population: DXA Analysis Set included all participants in the FAS with Baseline and Month 12 DXA assessment on the Q3M dosing regimen for lumbar spine as provided by the central imaging vendor.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score at 12 Months | 1.009 Z-score | Standard Error 0.119 |
Secondary
BTM - Bone-specific Alkaline Phosphatase (BSAP)
Time frame: Baseline and Days 10 and 30, and Months 3, 6, 9, 12, and 15
Population: BTM Analysis Set: includes all participants in the 3QM dosing regimen safety analysis set who had baseline and ≥ 1 postbaseline assessment for the BTM endpoint of interest on Q3M dosing regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | BTM - Bone-specific Alkaline Phosphatase (BSAP) | Baseline | 69.22 μg/L | Standard Deviation 34.26 |
| Denosumab 3-Month Dosing Regimen | BTM - Bone-specific Alkaline Phosphatase (BSAP) | Day 10 | 70.88 μg/L | Standard Deviation 32.77 |
| Denosumab 3-Month Dosing Regimen | BTM - Bone-specific Alkaline Phosphatase (BSAP) | Day 30 | 56.28 μg/L | Standard Deviation 28.32 |
| Denosumab 3-Month Dosing Regimen | BTM - Bone-specific Alkaline Phosphatase (BSAP) | Month 3 | 498.4 μg/L | Standard Deviation 332 |
| Denosumab 3-Month Dosing Regimen | BTM - Bone-specific Alkaline Phosphatase (BSAP) | Month 6 | 40.30 μg/L | Standard Deviation 22.58 |
| Denosumab 3-Month Dosing Regimen | BTM - Bone-specific Alkaline Phosphatase (BSAP) | Month 9 | 51.17 μg/L | Standard Deviation 106.27 |
| Denosumab 3-Month Dosing Regimen | BTM - Bone-specific Alkaline Phosphatase (BSAP) | Month 12 | 40.02 μg/L | Standard Deviation 27.64 |
| Denosumab 3-Month Dosing Regimen | BTM - Bone-specific Alkaline Phosphatase (BSAP) | Month 15 | 49.49 μg/L | Standard Deviation 31.2 |
Secondary
Change From Baseline in Child Health Questionnaire-Parent Form Physical Summary Score (CHQ-PF-50) at 12 Months
The CHQ-PF-50 was a 50-item questionnaire completed by the parents or guardians of children between 5 and 18 years of age. The 50 questions measure 14 domains which were summarized as the physical and psychological summary scores. Each summary score was transformed and could range from 0 to 100, with higher score indicating better physical and psychosocial health. A negative change from Baseline indicates decreased well-being.
Time frame: Baseline and 12 months
Population: Patient Reported Outcomes (PRO) Analysis Set: includes all participants in the FAS who had a baseline and ≥ 1 postbaseline valid PRO response on Q3M dosing regimen for the CHQ-PF-50. The CHQ-PF-50 analysis set only includes participants 5 years of age and older at screening.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Child Health Questionnaire-Parent Form Physical Summary Score (CHQ-PF-50) at 12 Months | -0.98 Score on a scale | Standard Deviation 15.41 |
Secondary
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index Score at 12 Months
The disability domain (questions 1-54) of the CHAQ was used to measure the participant's assessment of physical functioning or the parent's assessment of the child's physical functioning. The disability index comprised of 8 categories (dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and activities). Scoring ranged from 1 to 5; 1 was without any difficulty, 2 was with some difficulty, 3 was with much difficulty, and 4 was unable to do. An answer of not applicable was scored as a 5, but was not counted. If a child required assistance from another person or used an aid or other device for any of the 8 categories, the minimum score for that category was recorded as a 3. The CHAQ questions were scored and converted to a total index score ranging from 0 to 3. Negative change from Baseline indicates an improvement.
Time frame: Baseline and 12 months
Population: PRO Analysis Set includes all participants in the FAS who had a baseline and ≥ 1 postbaseline valid PRO response on Q3M dosing regimen for the CHAQ disability index score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index Score at 12 Months | -0.06 Score on a scale | Standard Deviation 0.46 |
Secondary
Change From Baseline in CHQ-PF-50 Psychological Summary Score at 12 Months
The CHQ-PF-50 was a 50-item questionnaire completed by the parents or guardians of children between 5 and 18 years of age. The 50 questions measure 14 domains which were summarized as the physical and psychological summary scores. Each summary score was transformed and could range from 0 to 100, with higher score indicating better physical and psychosocial health. A positive change from Baseline indicates improved well-being.
Time frame: Baseline and 12 months
Population: PRO Analysis Set includes all participants in the FAS who had a baseline and ≥ 1 postbaseline valid PRO response on Q3M dosing regimen for the CHQ-PF-50. The CHQ-PF-50 analysis set only includes participants 5 years of age and older at screening
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Change From Baseline in CHQ-PF-50 Psychological Summary Score at 12 Months | 0.85 Score on a scale | Standard Deviation 8.57 |
Secondary
Change From Baseline in Growth Velocity at 12 Months
Change from baseline in growth velocity was determined by calculating age-adjusted Z-scores for height, weight and body mass index (BMI). Height-for-age Z-score was defined as the difference between the participant's height and the median height for the population with the same age and gender, divided by the population standard deviation. The definitions of growth velocity based on weight and BMI were analogously calculated. To programmatically calculate the Z-scores, the National Center for Health Statistics percentiles growth charts, based on the 2000 Center for Disease Control and Prevention (CDC) (http://www.cdc.gov/growthcharts/c c\_charts.htm), and the CDC Anthropometric Software Package 3.0 Z-scores were used. During normal growth, the change in z-score for each of the three should equal 0. A positive change in any of the three indicates growth acceleration, whereas a negative change indicates deceleration.
Time frame: Baseline and 12 months
Population: Growth Velocity Analysis Set includes all participants in the FAS with non-missing height, weight, or BMI, as applicable, at Baseline and postbaseline on the Q3M dosing regimen. Only participants with observed data at Baseline and Month 12 are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Growth Velocity at 12 Months | Height -for-age Z-score | -0.01 Z-score | Standard Deviation 0.43 |
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Growth Velocity at 12 Months | Weight-for-age Z-score | 0.01 Z-score | Standard Deviation 0.53 |
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Growth Velocity at 12 Months | BMI-for-age Z-score | -0.07 Z-score | Standard Deviation 0.52 |
Secondary
Change From Baseline in Lumbar Spine BMD Z-score at 6 Months
Lumbar spine BMD was measured by DXA adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD.
Time frame: Baseline and 6 months
Population: DXA Analysis Set included all participants in the FAS with Baseline and Month 6 DXA assessment on the Q3M dosing regimen for lumbar spine as provided by the central imaging vendor.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Lumbar Spine BMD Z-score at 6 Months | 0.925 Z-score | Standard Error 0.078 |
Secondary
Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months
Proximal femur (total hip and femoral neck) BMD Z-score was measured by DXA adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD.
Time frame: Baseline, 6 and 12 months
Population: DXA Analysis Set included all participants in the FAS with Baseline, Month 6 and Month 12 DXA assessment on the Q3M dosing regimen for lumbar spine as provided by the central imaging vendor. Only participants 5 years of age or older are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months | Total hip BMD Z-score - 6 Months | 0.799 Z score | Standard Error 0.082 |
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months | Total hip BMD Z-score - 12 Months | 0.793 Z score | Standard Error 0.154 |
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months | Femoral neck BMD Z-score - 6 Months | 0.769 Z score | Standard Error 0.067 |
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months | Femoral neck BMD Z-score - 12 Months | 0.689 Z score | Standard Error 0.131 |
Secondary
Change From Baseline in Wong-Baker Faces Pain Rating Scale (WBFPRS) at 12 Months
Participants were asked to report their level of pain by choosing a face that best described their own pain (the corresponding number: 0, 2, 4, 6, 8, 10) were then recorded. The WBFPRS ranged from 0, no hurt, to 10, hurts worst. A negative change from baseline indicates an improvement.
Time frame: Baseline and 12 months
Population: Patient Reported Outcomes (PRO) Analysis Set: includes all participants in the FAS who had a baseline and ≥ 1 postbaseline valid PRO response on Q3M dosing regimen for the WBFPRS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Change From Baseline in Wong-Baker Faces Pain Rating Scale (WBFPRS) at 12 Months | 0.0 Score on a scale | Standard Deviation 1.7 |
Secondary
Percentage of Participants With at Least 1 Vertebral and Nonvertebral Fracture
Time frame: Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months
Population: Q3M Dosing Regimen Safety Analysis Set: includes all participants in the FAS who received ≥ 1 dose of Q3M dosing regimen. Only participants 5 years of age or older are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 3-Month Dosing Regimen | Percentage of Participants With at Least 1 Vertebral and Nonvertebral Fracture | 28.6 Percentage of participants |
| Denosumab 3-Month Dosing Regimen | Percentage of Participants With at Least 1 Vertebral and Nonvertebral Fracture | 30.4 Percentage of participants |
Secondary
Percentage of Participants With at Least 1 X-ray Confirmed Long Bone or New and Worsening Vertebral Fracture
Time frame: Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months
Population: Q3M Dosing Regimen Safety Analysis Set: includes all participants in the FAS who received ≥ 1 dose of Q3M dosing regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 3-Month Dosing Regimen | Percentage of Participants With at Least 1 X-ray Confirmed Long Bone or New and Worsening Vertebral Fracture | 28.3 Percentage of participants |
| Denosumab 3-Month Dosing Regimen | Percentage of Participants With at Least 1 X-ray Confirmed Long Bone or New and Worsening Vertebral Fracture | 26.7 Percentage of participants |
Secondary
Percentage of Participants With at Least 1 X-ray Confirmed New and Worsening Vertebral Fracture
Time frame: Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months
Population: The Vertebral Fracture Analysis Set: includes all participants in the FAS who had a readable non-missing baseline and ≥1 non-missing postbaseline X-ray vertebral evaluation on the Q3M dosing regimen as provided by the central imaging vendor.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 3-Month Dosing Regimen | Percentage of Participants With at Least 1 X-ray Confirmed New and Worsening Vertebral Fracture | 12.8 Percentage of participants |
| Denosumab 3-Month Dosing Regimen | Percentage of Participants With at Least 1 X-ray Confirmed New and Worsening Vertebral Fracture | 8.5 Percentage of participants |
Secondary
Percentage of Participants With at Least 1 X-ray Confirmed New Vertebral Fracture
Time frame: Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months
Population: The Vertebral Fracture Analysis Set: includes all participants in the FAS who had a readable non-missing baseline and ≥1 non-missing postbaseline X-ray vertebral evaluation on the Q3M dosing regimen as provided by the central imaging vendor.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 3-Month Dosing Regimen | Percentage of Participants With at Least 1 X-ray Confirmed New Vertebral Fracture | 10.6 Percentage of participants |
| Denosumab 3-Month Dosing Regimen | Percentage of Participants With at Least 1 X-ray Confirmed New Vertebral Fracture | 6.4 Percentage of participants |
Secondary
Percentage of Participants Wth at Least 1 X-ray Confirmed Improving Vertebral Fracture
Time frame: Q3M Dosing Regimen: Baseline up to 12 months
Population: The Vertebral Fracture Analysis Set: includes all participants in the FAS who had a readable non-missing baseline and ≥1 non-missing postbaseline X-ray vertebral evaluation on the Q3M dosing regimen as provided by the central imaging vendor.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 3-Month Dosing Regimen | Percentage of Participants Wth at Least 1 X-ray Confirmed Improving Vertebral Fracture | 27.7 Percentage of participants |
Secondary
Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide
Time frame: Baseline and Days 10 and 30, and Months 3, 6, 9, 12, 15 and 18
Population: BTM Analysis Set: includes all participants in the 3QM dosing regimen safety analysis set who had baseline and ≥ 1 postbaseline assessment for the BTM endpoint of interest on Q3M dosing regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Baseline | 1136.5 ng/L | Standard Deviation 569.7 |
| Denosumab 3-Month Dosing Regimen | Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Day 10 | 174.4 ng/L | Standard Deviation 64.7 |
| Denosumab 3-Month Dosing Regimen | Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Day 30 | 176.5 ng/L | Standard Deviation 87.9 |
| Denosumab 3-Month Dosing Regimen | Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Month 3 | 498.4 ng/L | Standard Deviation 332 |
| Denosumab 3-Month Dosing Regimen | Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Month 6 | 537.1 ng/L | Standard Deviation 427.1 |
| Denosumab 3-Month Dosing Regimen | Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Month 9 | 539.0 ng/L | Standard Deviation 425 |
| Denosumab 3-Month Dosing Regimen | Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Month 12 | 681.2 ng/L | Standard Deviation 563.1 |
| Denosumab 3-Month Dosing Regimen | Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Month 15 | 1050.8 ng/L | Standard Deviation 758.8 |
| Denosumab 3-Month Dosing Regimen | Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide | Month 18 | 1290.0 ng/L | — |
Secondary
Serum Concentration of Denosumab
Time frame: Days 1 (predose), 10, 30, and 60, & weeks 12, 24, 36, 48, 60, 72 (end of study visit), early termination visit, & follow-up visit 12 weeks after last dose (average duration of treatment: 231 days)
Population: PK Analysis Set includes all participants in the 3QM dosing regimen safety analysis set who had ≥ 1 serum denosumab reported result on 3QM dosing regimen at any 1 time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Day 1 | 8.1 ng/mL | Standard Deviation 62 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Day 10 | 6685.4 ng/mL | Standard Deviation 1761.8 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Day 30 | 3840.5 ng/mL | Standard Deviation 1329.9 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Day 60 | 1291.4 ng/mL | Standard Deviation 971.2 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Week 12 Day 1 | 406.2 ng/mL | Standard Deviation 627 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Week 24 Day 1 | 589.8 ng/mL | Standard Deviation 804.3 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Week 36 | 835.1 ng/mL | Standard Deviation 983.5 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Week 48 | 647.3 ng/mL | Standard Deviation 875.1 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Week 60 | 1266.7 ng/mL | Standard Deviation 861.1 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Week 72 | 970.0 ng/mL | Standard Deviation 1371.8 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Early Termination Visit | 4.2 ng/mL | Standard Deviation 11.8 |
| Denosumab 3-Month Dosing Regimen | Serum Concentration of Denosumab | Week 12 Follow-up Visit | 72.6 ng/mL | Standard Deviation 103.9 |