Osteogenesis Imperfecta, Type I, Osteogenesis Imperfecta Type III, Osteogenesis Imperfecta Type IV
Conditions
Keywords
Osteogenesis Imperfecta, Brittle Bone Disease
Brief summary
The purpose of this study is to select a suitable dose of BPS804 by measuring the strength/quality of bone using a special type of CT scanner. Participants will be treated for 12 months and followed up for a further 12 months.
Detailed description
This study was previously posted by Mereo Biopharma and was transferred to Ultragenyx in February 2021.
Interventions
DRUGsetrusumab
Intravenous infusion
DIETARY_SUPPLEMENTCalcium
tablets
DIETARY_SUPPLEMENTVitamin D
capsules
DRUGzoledronic acid (optional)
Following completion of the study treatment (Month 12) participants can receive an optional single dose of zoledronic acid. Participants can receive an optional further dose of zoledronic acid at Month 18 at the discretion of their treating physician.
Sponsors
Mereo BioPharma
Ultragenyx Pharmaceutical Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Sponsor will be masked until the primary analysis of the study except for open-label substudy treatment arm. The study site pharmacist will be unmasked to treatment allocation throughout. Study treatment will be monitored by a separate unmasked monitoring team.
Intervention model description
Double-blind, Dose-finding Study, incorporating an open-label substudy
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with a clinical diagnosis of OI Type I, III or IV with a confirmed defect in the COL1A1/COL1A2 genes, as confirmed by genetic testing * One or more fractures in the past 5 years * Capable of giving signed consent
Exclusion criteria
* History of skeletal malignancies or other bone diseases (other than OI) * History of neural foraminal stenosis (except if due to scoliosis) * History of myocardial infarction, angina pectoris, ischaemic stroke or transient ischaemic attack * History of endocrine or thyroid/parathyroid conditions that could affect bone metabolism * Treatment with bisphosphonates within 3 months of randomisation * Treatment with teraparatide, denosumab or other anabolic/anti-reabsorptive medications within 6 months of randomisation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12 | Baseline, Month 12 (end of treatment [EOT]) | Assessed by high resolution peripheral quantitative computed tomography (HRpQCT). HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presents the ratio of the means between the visit and Baseline from analysis of covariance (ANCOVA). |
| Change From Baseline in Radial Bone Strength (Failure Load) at Month 12 | Baseline, Month 12 (EOT) | Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius. |
| Change From Baseline in Radial Bone Strength (Stiffness) at Month 12 | Baseline, Month 12 (EOT) | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm | Baseline, Months 6, 12 (EOT) | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
| Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Baseline, Months 6, 12 (EOT), 18, 24 | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
| Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm | Baseline, Months 6, 12 (EOT) | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
| Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Month 12 (EOT) | Fracture assessment, confirmed by central radiographic reading, was carried out for peripheral including all major long bones, minor bone (digits, ribs) and vertebral fractures. Fractures without clinical symptoms, detected only by means of radiographic investigations, were not included in the analysis. |
| Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Baseline, Month 6 | BMD was evaluated by dual-energy x-ray absorptiometry (DXA). T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD. |
| Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Baseline, Month 6 | BMD was evaluated by DXA. |
| Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Baseline, Month 12 (EOT) | BMD was evaluated by DXA. T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD. |
| Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Baseline, Month 12 (EOT) | BMD was evaluated by DXA. |
| Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Baseline, Months 6, 12 (EOT), 18, and 24 | Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA. |
| Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Baseline, Months 6, 12 (EOT), 18, and 24 | Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA. |
| Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Baseline, Month 6, Month 12 (EOT) | — |
| Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Baseline, Months 6, 12 (EOT), 18, 24 | Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA. |
| Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Baseline, Months 1, 3, 6, 9, 12 (EOT) | — |
| Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Baseline, Months 1, 3, 6, 9, 12 (EOT) | — |
| Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12 | Baseline, Months 6, 12 (EOT) | The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Physical Component Summary ranges from 0 to 100, where higher scores reflect better physical functioning. |
| Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12 | Baseline, Months 6, 12 (EOT) | The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Mental Component Summary ranges from 0 to 100, where higher scores reflect better mental health functioning. |
| Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12 | Baseline, Months 6 and 12 (EOT) | The EQ-5D-5L is a standardised measure of health status comprised of a descriptive system of 5 health-related quality of life states (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) of overall health. Each dimension is rated on a 5-point response scale indicating severity of problems, where 1 is no problems and 5 is extreme problems. The 5 questions are scored and together contribute to the EQ-5D index (utility) score between 0 and 1 (1 being perfect health). |
| Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12 | Baseline, Months 6, 12 (EOT) | The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The total score is calculated on a 0-100 scale, where higher scores indicate a greater (negative) impact on quality of life. |
| Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12 | Baseline, Months 6, 12 (EOT) | The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Pain subscale ranges from 0 to 10, with higher value representing worse pain. |
| Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12 | Baseline, Months 6, 12 (EOT) | The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Activities subscale ranges from 0 to 100, with higher value representing increased difficulty. |
| Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | up to Month 14 | Serum samples were screened for antibodies binding to setrusumab using a validated assay method by or under the supervision of the sponsor. |
| Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.) | An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; is another important medical event. The intensity for each AE was graded as mild, moderate or severe, according to the investigator's judgement. An event was considered related to study drug if there were a reasonable possibility of a relationship, according to the investigator's clinical judgment. A TEAE was defined as an event occurring or worsening on or after the first dose of study medication. |
| Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Baseline, Months 6, 12 (EOT) | Lean and fat body mass was evaluated using whole body DXA (including the head). |
| Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm | Baseline, Months 6, 12 (EOT) | Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA. |
| Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Baseline, Months 6, 12 (EOT), 18, 24 | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
Countries
Canada, Denmark, France, United Kingdom, United States
Participant flow
Pre-assignment details
Participants were randomized 1:1:1:1 to 3 doses of setrusumab (20 mg/kg, 8 mg/kg and 2 mg/kg) and placebo for a 12-month Treatment Period. Per Protocol Amendment 4, participants originally randomized to the placebo group were reassigned to receive 20 mg/kg open-label setrusumab (1 discontinued study prior to the transition). Two participants in the setrusumab 20 mg/kg open-label group were randomized into this group after Amendment 4 and did not receive placebo.
Participants by arm
| Arm | Count |
|---|---|
| Setrusumab 20 mg/kg (Blinded) Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | 31 |
| Setrusumab 8 mg/kg (Blinded) Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | 29 |
| Setrusumab 2 mg/kg (Blinded) Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | 30 |
| Setrusumab 20 mg/kg (Open-Label) Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | 2 |
| Placebo Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. Due to a protocol amendment, placebo was actually received for an average of 5 months. | 20 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 2 | 3 | 1 | 0 | 1 |
| Overall Study | Other, Not Specified | 1 | 3 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 4 | 0 | 1 |
Baseline characteristics
| Characteristic | Setrusumab 20 mg/kg (Blinded) | Total | Placebo | Setrusumab 20 mg/kg (Open-Label) | Setrusumab 2 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|---|---|---|---|
| Age, Continuous | 40.6 years STANDARD_DEVIATION 13.73 | 42.4 years STANDARD_DEVIATION 13.8 | 40.9 years STANDARD_DEVIATION 14.68 | 43.5 years STANDARD_DEVIATION 14.85 | 47.2 years STANDARD_DEVIATION 12.42 | 40.4 years STANDARD_DEVIATION 14.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 103 Participants | 19 Participants | 2 Participants | 28 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Collected or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 29 Participants | 107 Participants | 20 Participants | 2 Participants | 29 Participants | 27 Participants |
| Sex: Female, Male Female | 17 Participants | 73 Participants | 14 Participants | 1 Participants | 21 Participants | 20 Participants |
| Sex: Female, Male Male | 14 Participants | 39 Participants | 6 Participants | 1 Participants | 9 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 29 | 0 / 30 | 0 / 21 | 0 / 20 |
| other Total, other adverse events | 29 / 31 | 28 / 29 | 27 / 30 | 19 / 21 | 16 / 20 |
| serious Total, serious adverse events | 4 / 31 | 7 / 29 | 7 / 30 | 5 / 21 | 2 / 20 |
Outcome results
Primary
Change From Baseline in Radial Bone Strength (Failure Load) at Month 12
Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius.
Time frame: Baseline, Month 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial Bone Strength (Failure Load) at Month 12 | 61.25 newton (N) | Standard Error 21.669 |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial Bone Strength (Failure Load) at Month 12 | 32.25 newton (N) | Standard Error 24.342 |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial Bone Strength (Failure Load) at Month 12 | 8.86 newton (N) | Standard Error 23.2 |
p-value: 0.006ANCOVA
p-value: 0.19ANCOVA
p-value: 0.704ANCOVA
Primary
Change From Baseline in Radial Bone Strength (Stiffness) at Month 12
Assessed by FEA of models generated from HRpQCT images of the distal radius.
Time frame: Baseline, Month 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial Bone Strength (Stiffness) at Month 12 | 1638.70 N/mm | Standard Error 625.808 |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial Bone Strength (Stiffness) at Month 12 | 1422.00 N/mm | Standard Error 703.275 |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial Bone Strength (Stiffness) at Month 12 | 209.89 N/mm | Standard Error 671.777 |
p-value: 0.011ANCOVA
p-value: 0.047ANCOVA
p-value: 0.756ANCOVA
Primary
Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12
Assessed by high resolution peripheral quantitative computed tomography (HRpQCT). HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presents the ratio of the means between the visit and Baseline from analysis of covariance (ANCOVA).
Time frame: Baseline, Month 12 (end of treatment [EOT])
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment (per protocol almost all efficacy endpoints were to be analyzed only in the blinded treatment arms). Participants with an assessment at given time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12 | 1.004 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12 | 0.993 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12 | 0.992 ratio |
p-value: 0.644ANCOVA
p-value: 0.485ANCOVA
p-value: 0.404ANCOVA
Secondary
Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12
Time frame: Baseline, Months 1, 3, 6, 9, 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 3 | 17.903 µg/L |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 9 | 7.265 µg/L |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 1 | 24.349 µg/L |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 6 | 13.096 µg/L |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 12 | 5.452 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 6 | 6.665 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 9 | 0.238 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 12 | 4.172 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 3 | 6.735 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 1 | 14.288 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 12 | 4.428 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 1 | 0.060 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 3 | 0.640 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 6 | -0.429 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 | Month 9 | -2.254 µg/L |
Comparison: Month 1p-value: <0.001ANCOVA
Comparison: Month 1p-value: <0.001ANCOVA
Comparison: Month 1p-value: 0.984ANCOVA
Comparison: Month 3p-value: <0.001ANCOVA
Comparison: Month 3p-value: 0.05ANCOVA
Comparison: Month 3p-value: 0.857ANCOVA
Comparison: Month 6p-value: 0.001ANCOVA
Comparison: Month 6p-value: 0.079ANCOVA
Comparison: Month 6p-value: 0.912ANCOVA
Comparison: Month 9p-value: 0.054ANCOVA
Comparison: Month 9p-value: 0.95ANCOVA
Comparison: Month 9p-value: 0.555ANCOVA
Comparison: Month 12p-value: 0.221ANCOVA
Comparison: Month 12p-value: 0.393ANCOVA
Comparison: Month 12p-value: 0.385ANCOVA
Secondary
Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12
Time frame: Baseline, Months 1, 3, 6, 9, 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 9 | -0.020 µg/L |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 6 | -0.013 µg/L |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 1 | -0.077 µg/L |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 3 | -0.044 µg/L |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 12 | -0.037 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 6 | -0.025 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 1 | -0.047 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 3 | -0.029 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 9 | -0.039 µg/L |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 12 | -0.002 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 12 | -0.034 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 9 | -0.031 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 1 | -0.041 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 6 | -0.028 µg/L |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 | Month 3 | -0.043 µg/L |
Comparison: Month 1p-value: <0.001ANCOVA
Comparison: Month 1p-value: <0.001ANCOVA
Comparison: Month 1p-value: <0.001ANCOVA
Comparison: Month 3p-value: 0.003ANCOVA
Comparison: Month 3p-value: 0.05ANCOVA
Comparison: Month 3p-value: 0.006ANCOVA
Comparison: Month 6p-value: 0.519ANCOVA
Comparison: Month 6p-value: 0.226ANCOVA
Comparison: Month 6p-value: 0.19ANCOVA
Comparison: Month 9p-value: 0.388ANCOVA
Comparison: Month 9p-value: 0.109ANCOVA
Comparison: Month 9p-value: 0.204ANCOVA
Comparison: Month 12p-value: 0.119ANCOVA
Comparison: Month 12p-value: 0.925ANCOVA
Comparison: Month 12p-value: 0.204ANCOVA
Secondary
Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time
Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.
Time frame: Baseline, Months 6, 12 (EOT), 18, and 24
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 18 | 1.024 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 24 | 1.011 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 12 | 1.017 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 18 | 1.011 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 12 | 1.005 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 24 | 1.020 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 6 | 1.004 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 6 | 1.012 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 18 | 1.001 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 24 | 1.018 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 6 | 0.997 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 6 | 1.002 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 12 | 1.003 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 12 | 1.004 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 18 | 1.004 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 24 | 1.017 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 6 | 0.998 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 12 | 0.998 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 6 | 0.998 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 24 | 0.996 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Tibial, Month 18 | 0.993 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 18 | 1.007 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 24 | 1.002 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time | Radial, Month 12 | 1.001 ratio |
Comparison: Radial, Month 6p-value: 0.285ANCOVA
Comparison: Radial, Month 6p-value: 0.544ANCOVA
Comparison: Radial, Month 6p-value: 0.615ANCOVA
Comparison: Radial, Month 12p-value: 0.179ANCOVA
Comparison: Radial, Month 12p-value: 0.513ANCOVA
Comparison: Radial, Month 12p-value: 0.849ANCOVA
Comparison: Radial, Month 18p-value: 0.037ANCOVA
Comparison: Radial, Month 18p-value: 0.88ANCOVA
Comparison: Radial, Month 18p-value: 0.153ANCOVA
Comparison: Radial, Month 24p-value: 0.073ANCOVA
Comparison: Radial, Month 24p-value: 0.007ANCOVA
Comparison: Radial, Month 24p-value: 0.791ANCOVA
Comparison: Tibial, Month 6p-value: 0.01ANCOVA
Comparison: Tibial, Month 6p-value: 0.553ANCOVA
Comparison: Tibial, Month 6p-value: 0.652ANCOVA
Comparison: Tibial, Month 12p-value: <0.001ANCOVA
Comparison: Tibial, Month 12p-value: 0.482ANCOVA
Comparison: Tibial, Month 12p-value: 0.685ANCOVA
Comparison: Tibial, Month 18p-value: 0.002ANCOVA
Comparison: Tibial, Month 18p-value: 0.672ANCOVA
Comparison: Tibial, Month 18p-value: 0.377ANCOVA
Comparison: Tibial, Month 24p-value: 0.015ANCOVA
Comparison: Tibial, Month 24p-value: 0.086ANCOVA
Comparison: Tibial, Month 24p-value: 0.712ANCOVA
Secondary
Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12
The EQ-5D-5L is a standardised measure of health status comprised of a descriptive system of 5 health-related quality of life states (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) of overall health. Each dimension is rated on a 5-point response scale indicating severity of problems, where 1 is no problems and 5 is extreme problems. The 5 questions are scored and together contribute to the EQ-5D index (utility) score between 0 and 1 (1 being perfect health).
Time frame: Baseline, Months 6 and 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12 | Month 6 | 0.0627 score on a scale |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12 | Month 12 | 0.0424 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12 | Month 12 | 0.0252 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12 | Month 6 | 0.0362 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12 | Month 6 | -0.0383 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12 | Month 12 | 0.0214 score on a scale |
Comparison: Month 6p-value: 0.092ANCOVA
Comparison: Month 6p-value: 0.31ANCOVA
Comparison: Month 6p-value: 0.304ANCOVA
Comparison: Month 12p-value: 0.155ANCOVA
Comparison: Month 12p-value: 0.392ANCOVA
Comparison: Month 12p-value: 0.464ANCOVA
Secondary
Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12
Lean and fat body mass was evaluated using whole body DXA (including the head).
Time frame: Baseline, Months 6, 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 6: Lean | 519.152 grams |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 12: Lean | 867.668 grams |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 6: Fat | 42.567 grams |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 12: Fat | 421.266 grams |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 12: Fat | -85.495 grams |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 6: Lean | -410.664 grams |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 6: Fat | 105.420 grams |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 12: Lean | -225.474 grams |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 12: Fat | 792.485 grams |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 12: Lean | 184.164 grams |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 6: Fat | 426.388 grams |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 | Month 6: Lean | 168.206 grams |
Comparison: Lean, Month 6p-value: 0.045ANCOVA
Comparison: Lean, Month 6p-value: 0.101ANCOVA
Comparison: Lean, Month 6p-value: 0.482ANCOVA
Comparison: Lean, Month 12p-value: 0.011ANCOVA
Comparison: Lean, Month 12p-value: 0.508ANCOVA
Comparison: Lean, Month 12p-value: 0.563ANCOVA
Comparison: Fat, Month 6p-value: 0.917ANCOVA
Comparison: Fat, Month 6p-value: 0.789ANCOVA
Comparison: Fat, Month 6p-value: 0.262ANCOVA
Comparison: Fat, Month 12p-value: 0.426ANCOVA
Comparison: Fat, Month 12p-value: 0.871ANCOVA
Comparison: Fat, Month 12p-value: 0.113ANCOVA
Secondary
Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12
BMD was evaluated by DXA.
Time frame: Baseline, Month 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Femoral Neck | 3.30 g/cm^2 |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Total Body | 1.98 g/cm^2 |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Lumbar | 8.55 g/cm^2 |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Femoral Neck | 2.65 g/cm^2 |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Lumbar | 6.79 g/cm^2 |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Total Body | 2.03 g/cm^2 |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Femoral Neck | 1.90 g/cm^2 |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Lumbar | 2.50 g/cm^2 |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 | Total Body | 1.06 g/cm^2 |
Comparison: Lumbarp-value: <0.001ANCOVA
Comparison: Lumbarp-value: <0.001ANCOVA
Comparison: Lumbarp-value: 0.035ANCOVA
Comparison: Total bodyp-value: 0.003ANCOVA
Comparison: Total bodyp-value: 0.003ANCOVA
Comparison: Total bodyp-value: 0.088ANCOVA
Comparison: Femoral neckp-value: 0.016ANCOVA
Comparison: Femoral neckp-value: 0.068ANCOVA
Comparison: Femoral neckp-value: 0.16ANCOVA
Secondary
Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6
BMD was evaluated by DXA.
Time frame: Baseline, Month 6
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Femoral Neck | -0.42 g/cm^2 |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Lumbar | 4.06 g/cm^2 |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Total Body | 0.77 g/cm^2 |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Total Body | 0.83 g/cm^2 |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Lumbar | 4.70 g/cm^2 |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Femoral Neck | 1.64 g/cm^2 |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Lumbar | 1.58 g/cm^2 |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Femoral Neck | 1.61 g/cm^2 |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 | Total Body | 1.21 g/cm^2 |
Comparison: Lumbarp-value: <0.001ANCOVA
Comparison: Lumbarp-value: <0.001ANCOVA
Comparison: Lumbarp-value: 0.088ANCOVA
Comparison: Total bodyp-value: 0.184ANCOVA
Comparison: Total bodyp-value: 0.144ANCOVA
Comparison: Total bodyp-value: 0.028ANCOVA
Comparison: Femoral neckp-value: 0.694ANCOVA
Comparison: Femoral neckp-value: 0.143ANCOVA
Comparison: Femoral neckp-value: 0.111ANCOVA
Secondary
Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12
BMD was evaluated by DXA. T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD.
Time frame: Baseline, Month 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Total Body | 0.181 T-score |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Lumbar | 0.587 T-score |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Femoral Neck | 0.163 T-score |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Total Body | 0.199 T-score |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Lumbar | 0.486 T-score |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Femoral Neck | 0.159 T-score |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Lumbar | 0.174 T-score |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Femoral Neck | 0.104 T-score |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 | Total Body | 0.108 T-score |
Comparison: Lumbarp-value: <0.001ANCOVA
Comparison: Lumbarp-value: <0.001ANCOVA
Comparison: Lumbarp-value: 0.026ANCOVA
Comparison: Total bodyp-value: 0.007ANCOVA
Comparison: Total bodyp-value: 0.004ANCOVA
Comparison: Total bodyp-value: 0.085ANCOVA
Comparison: Femoral neckp-value: 0.04ANCOVA
Comparison: Femoral neckp-value: 0.061ANCOVA
Comparison: Femoral neckp-value: 0.189ANCOVA
Secondary
Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6
BMD was evaluated by dual-energy x-ray absorptiometry (DXA). T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD.
Time frame: Baseline, Month 6
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Total Body | 0.072 T-score |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Lumbar | 0.273 T-score |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Femoral Neck | -0.024 T-score |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Total Body | 0.071 T-score |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Lumbar | 0.338 T-score |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Femoral Neck | 0.102 T-score |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Lumbar | 0.110 T-score |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Femoral Neck | 0.087 T-score |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 | Total Body | 0.122 T-score |
Comparison: Lumbarp-value: <0.001ANCOVA
Comparison: Lumbarp-value: <0.001ANCOVA
Comparison: Lumbarp-value: 0.08ANCOVA
Comparison: Total bodyp-value: 0.238ANCOVA
Comparison: Total bodyp-value: 0.238ANCOVA
Comparison: Total bodyp-value: 0.035ANCOVA
Comparison: Femoral neckp-value: 0.687ANCOVA
Comparison: Femoral neckp-value: 0.107ANCOVA
Comparison: Femoral neckp-value: 0.128ANCOVA
Secondary
Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12
The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Activities subscale ranges from 0 to 100, with higher value representing increased difficulty.
Time frame: Baseline, Months 6, 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12 | Month 6 | -5.980 score on a scale |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12 | Month 12 | -0.964 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12 | Month 6 | -2.722 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12 | Month 12 | 4.489 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12 | Month 6 | 1.907 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12 | Month 12 | -1.630 score on a scale |
Comparison: Month 6p-value: 0.037ANCOVA
Comparison: Month 6p-value: 0.342ANCOVA
Comparison: Month 6p-value: 0.515ANCOVA
Comparison: Month 12p-value: 0.786ANCOVA
Comparison: Month 12p-value: 0.212ANCOVA
Comparison: Month 12p-value: 0.655ANCOVA
Secondary
Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12
The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Pain subscale ranges from 0 to 10, with higher value representing worse pain.
Time frame: Baseline, Months 6, 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12 | Month 6 | -3.990 score on a scale |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12 | Month 12 | -3.655 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12 | Month 6 | -3.906 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12 | Month 12 | -4.968 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12 | Month 6 | -6.003 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12 | Month 12 | -7.178 score on a scale |
Comparison: Month 6p-value: 0.278ANCOVA
Comparison: Month 6p-value: 0.292ANCOVA
Comparison: Month 6p-value: 0.115ANCOVA
Comparison: Month 12p-value: 0.356ANCOVA
Comparison: Month 12p-value: 0.205ANCOVA
Comparison: Month 12p-value: 0.078ANCOVA
Secondary
Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12
The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The total score is calculated on a 0-100 scale, where higher scores indicate a greater (negative) impact on quality of life.
Time frame: Baseline, Months 6, 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12 | Month 6 | -3.584 score on a scale |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12 | Month 12 | -1.668 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12 | Month 6 | -1.848 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12 | Month 12 | -0.587 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12 | Month 6 | -0.649 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12 | Month 12 | -3.846 score on a scale |
Comparison: Month 6p-value: 0.15ANCOVA
Comparison: Month 6p-value: 0.468ANCOVA
Comparison: Month 6p-value: 0.8ANCOVA
Comparison: Month 12p-value: 0.563ANCOVA
Comparison: Month 12p-value: 0.839ANCOVA
Comparison: Month 12p-value: 0.186ANCOVA
Secondary
Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set
Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.
Time frame: Baseline, Months 6, 12 (EOT), 18, 24
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 24 | 1.000 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 6 | 1.007 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 12 | 1.004 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 18 | 1.002 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 24 | 0.997 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 6 | 1.004 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 12 | 0.991 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 18 | 0.989 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 12 | 0.993 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 18 | 0.992 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 24 | 0.998 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 18 | 1.042 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 6 | 1.016 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 24 | 1.062 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 6 | 1.000 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 12 | 1.018 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 6 | 0.990 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 12 | 0.992 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 12 | 0.973 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 18 | 0.979 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 18 | 0.983 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 6 | 0.998 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Radial: Month 24 | 0.979 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set | Tibial: Month 24 | 1.017 ratio |
Comparison: Radial, Month 6p-value: 0.329ANCOVA
Comparison: Radial, Month 6p-value: 0.953ANCOVA
Comparison: Radial, Month 6p-value: 0.795ANCOVA
Comparison: Radial, Month 12p-value: 0.644ANCOVA
Comparison: Radial, Month 12p-value: 0.485ANCOVA
Comparison: Radial, Month 12p-value: 0.404ANCOVA
Comparison: Radial, Month 18p-value: 0.827ANCOVA
Comparison: Radial, Month 18p-value: 0.459ANCOVA
Comparison: Radial, Month 18p-value: 0.022ANCOVA
Comparison: Radial, Month 24p-value: 0.821ANCOVA
Comparison: Radial, Month 24p-value: 0.911ANCOVA
Comparison: Radial, Month 24p-value: 0.152ANCOVA
Comparison: Tibial, Month 6p-value: 0.668ANCOVA
Comparison: Tibial, Month 6p-value: 0.109ANCOVA
Comparison: Tibial, Month 6p-value: 0.358ANCOVA
Comparison: Tibial, Month 12p-value: 0.742ANCOVA
Comparison: Tibial, Month 12p-value: 0.567ANCOVA
Comparison: Tibial, Month 12p-value: 0.43ANCOVA
Comparison: Tibial, Month 18p-value: 0.634ANCOVA
Comparison: Tibial, Month 18p-value: 0.146ANCOVA
Comparison: Tibial, Month 18p-value: 0.521ANCOVA
Comparison: Tibial, Month 24p-value: 0.991ANCOVA
Comparison: Tibial, Month 24p-value: 0.069ANCOVA
Comparison: Tibial, Month 24p-value: 0.625ANCOVA
Secondary
Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12
The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Mental Component Summary ranges from 0 to 100, where higher scores reflect better mental health functioning.
Time frame: Baseline, Months 6, 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12 | Month 6 | 0.966 score on a scale |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12 | Month 12 | 2.807 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12 | Month 6 | -0.492 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12 | Month 12 | -1.473 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12 | Month 6 | -1.133 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12 | Month 12 | -1.664 score on a scale |
Comparison: Month 6p-value: 0.527ANCOVA
Comparison: Month 6p-value: 0.738ANCOVA
Comparison: Month 6p-value: 0.465ANCOVA
Comparison: Month 12p-value: 0.068ANCOVA
Comparison: Month 12p-value: 0.328ANCOVA
Comparison: Month 12p-value: 0.277ANCOVA
Secondary
Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12
The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Physical Component Summary ranges from 0 to 100, where higher scores reflect better physical functioning.
Time frame: Baseline, Months 6, 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12 | Month 6 | 0.672 score on a scale |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12 | Month 12 | -1.178 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12 | Month 6 | -0.463 score on a scale |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12 | Month 12 | -0.994 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12 | Month 6 | 1.342 score on a scale |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12 | Month 12 | 2.171 score on a scale |
Comparison: Month 12p-value: 0.354ANCOVA
Comparison: Month 6p-value: 0.588ANCOVA
Comparison: Month 6p-value: 0.697ANCOVA
Comparison: Month 6p-value: 0.283ANCOVA
Comparison: Month 12p-value: 0.43ANCOVA
Comparison: Month 12p-value: 0.091ANCOVA
Secondary
Change From Baseline in Total vBMD (Radial and Tibial) Over Time
Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.
Time frame: Baseline, Months 6, 12 (EOT), 18, and 24
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 6 | 1.011 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 12 | 1.017 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 18 | 1.013 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 24 | 0.998 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 6 | 1.017 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 12 | 1.024 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 18 | 1.020 ratio |
| Setrusumab 20 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 24 | 1.001 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 18 | 0.992 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 18 | 1.021 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 24 | 1.009 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 6 | 1.011 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 12 | 1.011 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 6 | 0.995 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 12 | 1.008 ratio |
| Setrusumab 8 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 24 | 1.025 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 18 | 0.996 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 12 | 0.999 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 6 | 1.000 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Radial, Month 24 | 0.985 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 18 | 0.987 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 12 | 0.989 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 6 | 0.995 ratio |
| Setrusumab 2 mg/kg (Blinded) | Change From Baseline in Total vBMD (Radial and Tibial) Over Time | Tibial, Month 24 | 0.994 ratio |
Comparison: Radial, Month 6p-value: 0.065ANCOVA
Comparison: Radial, Month 6p-value: 0.405ANCOVA
Comparison: Radial, Month 6p-value: 0.966ANCOVA
Comparison: Radial, Month 12p-value: 0.003ANCOVA
Comparison: Radial, Month 12p-value: 0.229ANCOVA
Comparison: Radial, Month 12p-value: 0.807ANCOVA
Comparison: Radial, Month 18p-value: 0.042ANCOVA
Comparison: Radial, Month 18p-value: 0.283ANCOVA
Comparison: Radial, Month 18p-value: 0.536ANCOVA
Comparison: Radial, Month 24p-value: 0.765ANCOVA
Comparison: Radial, Month 24p-value: 0.247ANCOVA
Comparison: Radial, Month 24p-value: 0.05ANCOVA
Comparison: Tibial, Month 6p-value: 0.037ANCOVA
Comparison: Tibial, Month 6p-value: 0.174ANCOVA
Comparison: Tibial, Month 6p-value: 0.558ANCOVA
Comparison: Tibial, Month 12p-value: 0.02ANCOVA
Comparison: Tibial, Month 12p-value: 0.346ANCOVA
Comparison: Tibial, Month 12p-value: 0.387ANCOVA
Comparison: Tibial, Month 18p-value: 0.093ANCOVA
Comparison: Tibial, Month 18p-value: 0.156ANCOVA
Comparison: Tibial, Month 18p-value: 0.324ANCOVA
Comparison: Tibial, Month 24p-value: 0.92ANCOVA
Comparison: Tibial, Month 24p-value: 0.04ANCOVA
Comparison: Tibial, Month 24p-value: 0.643ANCOVA
Secondary
Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm
Assessed by FEA of models generated from HRpQCT images of the distal radius.
Time frame: Baseline, Months 6, 12 (EOT)
Population: All participants in the open-label arm who took at least 1 dose of study treatment. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm | Radial: Month 6 | 110.16 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm | Radial: Month 12 | 88.32 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm | Tibial: Month 6 | 69.78 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm | Tibial: Month 12 | 112.92 N |
Comparison: Radial, Month 6p-value: <0.001ANCOVA
Comparison: Radial, Month 12p-value: 0.004ANCOVA
Comparison: Tibial, Month 6p-value: 0.08ANCOVA
Comparison: Tibial, Month 12p-value: 0.031ANCOVA
Secondary
Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set
Assessed by FEA of models generated from HRpQCT images of the distal radius.
Time frame: Baseline, Months 6, 12 (EOT), 18, 24
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 12 | 76.15 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 24 | -19.59 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 24 | -24.75 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 6 | 46.00 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 18 | 50.69 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 18 | 50.39 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 6 | 31.22 N |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 12 | 61.25 N |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 6 | 39.95 N |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 12 | 32.25 N |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 18 | 43.11 N |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 24 | 45.03 N |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 6 | 45.91 N |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 12 | 60.20 N |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 18 | 88.33 N |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 24 | 41.37 N |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 6 | -3.28 N |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 12 | -65.96 N |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 12 | 8.86 N |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 24 | -74.94 N |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 24 | -50.65 N |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 18 | -49.50 N |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Tibial: Month 6 | -65.33 N |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set | Radial: Month 18 | -10.53 N |
Comparison: Radial, Month 6p-value: 0.064ANCOVA
Comparison: Radial, Month 6p-value: 0.019ANCOVA
Comparison: Radial, Month 6p-value: 0.845ANCOVA
Comparison: Radial, Month 12p-value: 0.006ANCOVA
Comparison: Radial, Month 12p-value: 0.19ANCOVA
Comparison: Radial, Month 12p-value: 0.704ANCOVA
Comparison: Radial, Month 18p-value: 0.002ANCOVA
Comparison: Radial, Month 18p-value: 0.021ANCOVA
Comparison: Radial, Month 18p-value: 0.504ANCOVA
Comparison: Radial, Month 24p-value: 0.462ANCOVA
Comparison: Radial, Month 24p-value: 0.134ANCOVA
Comparison: Radial, Month 24p-value: 0.086ANCOVA
Comparison: Tibial, Month 6p-value: 0.199ANCOVA
Comparison: Tibial, Month 8p-value: 0.219ANCOVA
Comparison: Tibial, Month 6p-value: 0.112ANCOVA
Comparison: Tibial, Month 12p-value: 0.086ANCOVA
Comparison: Tibial, Month 12p-value: 0.245ANCOVA
Comparison: Tibial, Month 12p-value: 0.232ANCOVA
Comparison: Tibial, Month 18p-value: 0.237ANCOVA
Comparison: Tibial, Month 18p-value: 0.088ANCOVA
Comparison: Tibial, Month 18p-value: 0.302ANCOVA
Comparison: Tibial, Month 24p-value: 0.626ANCOVA
Comparison: Tibial, Month 8p-value: 0.517ANCOVA
Comparison: Tibial, Month 24p-value: 0.262ANCOVA
Secondary
Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm
Assessed by FEA of models generated from HRpQCT images of the distal radius.
Time frame: Baseline, Months 6, 12 (EOT)
Population: All participants in the open-label arm who took at least 1 dose of study treatment. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm | Tibial: Month 6 | 4225.92 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm | Tibial: Month 12 | 5827.81 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm | Radial: Month 6 | 5056.51 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm | Radial: Month 12 | 4992.82 N/mm |
Comparison: Radial, Month 6p-value: <0.001ANCOVA
Comparison: Radial, Month 12p-value: <0.001ANCOVA
Comparison: Tibial, Month 6p-value: <0.001ANCOVA
Comparison: Tibial, Month 12p-value: <0.001ANCOVA
Secondary
Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set
Assessed by FEA of models generated from HRpQCT images of the distal radius.
Time frame: Baseline, Months 6, 12 (EOT), 18, 24
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 24 | -1250.69 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 12 | 2326.63 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 24 | -625.46 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 6 | 1344.84 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 12 | 1638.70 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 6 | 795.67 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 18 | 1047.16 N/mm |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 18 | 1295.98 N/mm |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 24 | 1172.45 N/mm |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 6 | 1048.61 N/mm |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 12 | 1422.00 N/mm |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 18 | 803.50 N/mm |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 6 | 1051.40 N/mm |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 12 | 1543.85 N/mm |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 18 | 1697.21 N/mm |
| Setrusumab 8 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 24 | 622.77 N/mm |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 6 | 109.65 N/mm |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 12 | -1428.87 N/mm |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 12 | 209.89 N/mm |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 24 | -1844.84 N/mm |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 24 | -1258.55 N/mm |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 18 | -815.38 N/mm |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Tibial: Month 6 | -1356.71 N/mm |
| Setrusumab 2 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set | Radial: Month 18 | -215.92 N/mm |
Comparison: Radial, Month 6p-value: 0.06ANCOVA
Comparison: Radial, Month 6p-value: 0.015ANCOVA
Comparison: Radial, Month 6p-value: 0.795ANCOVA
Comparison: Radial, Month 12p-value: 0.011ANCOVA
Comparison: Radial, Month 12p-value: 0.047ANCOVA
Comparison: Radial, Month 12p-value: 0.756ANCOVA
Comparison: Radial, Month 18p-value: 0.006ANCOVA
Comparison: Radial, Month 18p-value: 0.137ANCOVA
Comparison: Radial, Month 18p-value: 0.639ANCOVA
Comparison: Radial, Month 24p-value: 0.325ANCOVA
Comparison: Radial, Month 24p-value: 0.108ANCOVA
Comparison: Radial, Month 24p-value: 0.078ANCOVA
Comparison: Tibial, Month 6p-value: 0.106ANCOVA
Comparison: Tibial, Month 6p-value: 0.236ANCOVA
Comparison: Tibial, Month 6p-value: 0.164ANCOVA
Comparison: Tibial, Month 12p-value: 0.031ANCOVA
Comparison: Tibial, Month 12p-value: 0.224ANCOVA
Comparison: Tibial, Month 12p-value: 0.291ANCOVA
Comparison: Tibial, Month 18p-value: 0.324ANCOVA
Comparison: Tibial, Month 18p-value: 0.188ANCOVA
Comparison: Tibial, Month 18p-value: 0.503ANCOVA
Comparison: Tibial, Month 24p-value: 0.385ANCOVA
Comparison: Tibial, Month 24p-value: 0.727ANCOVA
Comparison: Tibial, Month 24p-value: 0.338ANCOVA
Secondary
Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm
Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.
Time frame: Baseline, Months 6, 12 (EOT)
Population: All participants in the open-label arm who took at least 1 dose of study treatment. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm | Radial: Month 6 | 0.994 ratio |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm | Radial: Month 12 | 1.011 ratio |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm | Tibial: Month 6 | 1.013 ratio |
| Setrusumab 20 mg/kg (Blinded) | Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm | Tibial: Month 12 | 1.035 ratio |
Comparison: Radial, Month 6p-value: 0.615ANCOVA
Comparison: Radial, Month 12p-value: 0.376ANCOVA
Comparison: Tibial, Month 6p-value: 0.259ANCOVA
Comparison: Tibial, Month 12p-value: 0.253ANCOVA
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set
Time frame: Baseline, Month 6, Month 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 6: Body Height | 0 Participants |
| Setrusumab 20 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 6: Weight | 0 Participants |
| Setrusumab 20 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 6: BMI | 0 Participants |
| Setrusumab 20 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 12: Body Height | 0 Participants |
| Setrusumab 20 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 12: Weight | 0 Participants |
| Setrusumab 20 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 12: BMI | 0 Participants |
| Setrusumab 8 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 12: BMI | 0 Participants |
| Setrusumab 8 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 6: Body Height | 0 Participants |
| Setrusumab 8 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 12: Body Height | 0 Participants |
| Setrusumab 8 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 12: Weight | 0 Participants |
| Setrusumab 8 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 6: Weight | 0 Participants |
| Setrusumab 8 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 6: BMI | 0 Participants |
| Setrusumab 2 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 6: Weight | 0 Participants |
| Setrusumab 2 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 6: BMI | 0 Participants |
| Setrusumab 2 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 12: BMI | 0 Participants |
| Setrusumab 2 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 12: Body Height | 0 Participants |
| Setrusumab 2 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 6: Body Height | 0 Participants |
| Setrusumab 2 mg/kg (Blinded) | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set | Month 12: Weight | 0 Participants |
Secondary
Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14
Serum samples were screened for antibodies binding to setrusumab using a validated assay method by or under the supervision of the sponsor.
Time frame: up to Month 14
Population: Safety Population: all participants who received at least 1 dose of study drug. The 19 participants who transitioned from the Placebo arm to the Setrusumab 20 mg/kg Open-Label arm are reflected in both arms for this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Binding Antibodies | 16.1 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Both Binding and Neutralizing Antibodies | 16.1 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Neutralizing Antibodies | 16.1 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Neutralizing Antibodies | 17.2 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Binding Antibodies | 17.2 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Both Binding and Neutralizing Antibodies | 17.2 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Neutralizing Antibodies | 16.7 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Binding Antibodies | 16.7 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Both Binding and Neutralizing Antibodies | 16.7 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Binding Antibodies | 9.5 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Both Binding and Neutralizing Antibodies | 0 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Neutralizing Antibodies | 0 percentage of participants |
| Placebo | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Neutralizing Antibodies | 0 percentage of participants |
| Placebo | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Binding Antibodies | 15.0 percentage of participants |
| Placebo | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 | Both Binding and Neutralizing Antibodies | 0 percentage of participants |
Secondary
Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death
An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; is another important medical event. The intensity for each AE was graded as mild, moderate or severe, according to the investigator's judgement. An event was considered related to study drug if there were a reasonable possibility of a relationship, according to the investigator's clinical judgment. A TEAE was defined as an event occurring or worsening on or after the first dose of study medication.
Time frame: Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.)
Population: Safety Population: all participants who received at least 1 dose of study drug. The 19 participants who transitioned from the Placebo arm to the Setrusumab 20 mg/kg Open-Label arm are reflected in both arms for this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Permanent Study Treatment Discontinuation | 6.5 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs | 100.0 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related Serious TEAEs | 6.5 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Death | 0 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Serious TEAEs | 12.9 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | All AEs | 100.0 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related TEAEs | 71.0 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related TEAEs | 41.4 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Permanent Study Treatment Discontinuation | 0 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs | 96.6 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Death | 0 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Serious TEAEs | 24.1 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | All AEs | 96.6 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related Serious TEAEs | 0 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related TEAEs | 36.7 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Permanent Study Treatment Discontinuation | 0 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | All AEs | 90.0 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs | 90.0 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related Serious TEAEs | 0 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Serious TEAEs | 23.3 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Death | 0 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | All AEs | 100.0 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related TEAEs | 42.9 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Permanent Study Treatment Discontinuation | 9.5 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Serious TEAEs | 23.8 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related Serious TEAEs | 9.5 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs | 95.2 percentage of participants |
| Setrusumab 20 mg/kg (Open-Label) | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Death | 0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Permanent Study Treatment Discontinuation | 5.0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | All AEs | 90.0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs | 80.0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related TEAEs | 25.0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Serious TEAEs | 10.0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | TEAEs Leading to Death | 0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death | Treatment-Related Serious TEAEs | 0 percentage of participants |
Secondary
Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12
Fracture assessment, confirmed by central radiographic reading, was carried out for peripheral including all major long bones, minor bone (digits, ribs) and vertebral fractures. Fractures without clinical symptoms, detected only by means of radiographic investigations, were not included in the analysis.
Time frame: Month 12 (EOT)
Population: Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Peripheral | 6.5 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Long-Bone | 3.2 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Any | 16.1 percentage of participants |
| Setrusumab 20 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Vertebral | 0 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Peripheral | 17.2 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Vertebral | 0 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Long-Bone | 13.8 percentage of participants |
| Setrusumab 8 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Any | 34.5 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Long-Bone | 3.3 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Peripheral | 13.3 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Vertebral | 0 percentage of participants |
| Setrusumab 2 mg/kg (Blinded) | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 | Any | 23.3 percentage of participants |