Fracture Healing
Conditions
Keywords
Fracture Healing, Tibial Diaphyseal Fracture
Brief summary
The primary objective of this study is to investigate the effect of romosozumab compared with placebo on time to radiographic healing of fresh tibial diaphyseal fractures (fractures in the midsection of the shinbone).
Interventions
BIOLOGICALRomosozumab
Administered by subcutaneous injection
DRUGPlacebo
Administered by subcutaneous injection
Sponsors
UCB Pharma
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Skeletally mature adults, age 18 to 85 years with radiographically closed growth plates * Fresh unilateral closed or Gustilo type I or type II open tibial fracture * Definitive fracture fixation with reamed (closed and open fractures) or unreamed (open fractures only) intramedullary nailing
Exclusion criteria
* Major polytrauma or significant axial trauma * Associated lower extremity fracture that will delay subject's ability to bear weight beyond the normal time expected for a tibial shaft fracture * Use of bone grafts at the time of fracture fixation * Pathological fracture or metabolic or bone disease * History of symptomatic spinal stenosis or facial nerve paralysis * Malignancy within the last 5 years * Evidence of the following (currently or within the past 5 years): elevated transaminases, significantly impaired renal function, current hyper- or hypocalcaemia * Use of agents affecting bone metabolism * Subject refuses to use appropriate methods of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Radiographic Healing | 52 weeks | Time to radiographic healing was defined as the time from intramedullary (IM) nailing to the first occurrence of bridging of 3 out of 4 cortices. Radiographic fracture healing was determined by a panel of independent reviewers (orthopedic/trauma surgeons and radiologists) blinded to treatment. The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 8 and weeks 12, 16, 20, 24, 36, and 52 | The Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2, is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning domain includes 10 questions that assess limitations in physical activities because of health problems. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. The range of SF-36 physical functioning is 14.94 - 57.03. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement in physical functioning. |
| Number of Participants With Unplanned Revision Surgeries | 52 weeks | — |
| Time to Clinical Healing | 52 weeks | Time to clinical healing was defined as the time from the IM nailing surgery date to the first date that both the score for ability to bear weight on the fractured limb and the score for absence of pain at the fracture site were equal to 6. The score for the ability to bear weight on the fractured limb was based on the ability to stand on affected leg without assistive device and the ability to walk without assistive device. The score ranges from 0 (unable to bear full body weight on the fractured limb) to 6 (able to bear full body weight on the fractured limb). Absence of pain at the fracture site was based on the absence of pain at the fracture site when applying direct pressure to the fracture site and applying a stress to the fracture site. The score ranges from 0 (pain without palpation at fracture site) to 6 (total absence of pain at fracture site). Time to clinical healing was estimated using CIF; unplanned revision surgery was considered a competing risk in CIF estimate. |
Countries
Australia, Bulgaria, Canada, Denmark, Estonia, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Latvia, Lithuania, Mexico, New Zealand, Norway, Poland, Romania, Russia, Slovakia, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 66 centers in Europe, India, North America, Australia, New Zealand, Hong Kong, and Mexico. Participants were enrolled from 02 September 2009 to 19 September 2011.
Pre-assignment details
Participants were randomized 1:1:1:1:1:1:1:1:1:3 to 1 of 9 romosozumab treatment groups or placebo. Randomization followed surgery and was stratified by type of fracture and definitive fracture fixation.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. | 103 |
| Romosozumab 70 mg: 2 Doses Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. | 34 |
| Romosozumab 70 mg: 3 Doses Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. | 34 |
| Romosozumab 70 mg: 4 Doses Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. | 33 |
| Romosozumab 140 mg: 2 Doses Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. | 33 |
| Romosozumab 140 mg: 3 Doses Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. | 33 |
| Romosozumab 140 mg: 4 Doses Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. | 33 |
| Romosozumab 210 mg: 2 Doses Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. | 33 |
| Romosozumab 210 mg: 3 Doses Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. | 31 |
| Romosozumab 210 mg: 4 Doses Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12. | 35 |
| Total | 402 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Ineligibility Determined | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 9 | 1 | 0 | 2 | 0 | 3 | 2 | 2 | 0 | 4 |
| Overall Study | Noncompliance | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 2 | 0 | 0 |
| Overall Study | Protocol Deviation | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 2 | 1 | 1 | 1 | 5 | 3 | 2 | 4 | 2 |
Baseline characteristics
| Characteristic | Placebo | Romosozumab 70 mg: 2 Doses | Romosozumab 70 mg: 3 Doses | Romosozumab 70 mg: 4 Doses | Romosozumab 140 mg: 2 Doses | Romosozumab 140 mg: 3 Doses | Romosozumab 140 mg: 4 Doses | Romosozumab 210 mg: 2 Doses | Romosozumab 210 mg: 3 Doses | Romosozumab 210 mg: 4 Doses | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 40.3 years STANDARD_DEVIATION 13.8 | 38.6 years STANDARD_DEVIATION 13.8 | 43.2 years STANDARD_DEVIATION 17.7 | 45.9 years STANDARD_DEVIATION 15.6 | 41.3 years STANDARD_DEVIATION 13.7 | 41.0 years STANDARD_DEVIATION 14.9 | 38.7 years STANDARD_DEVIATION 12.7 | 42.8 years STANDARD_DEVIATION 13.7 | 36.8 years STANDARD_DEVIATION 13.8 | 41.7 years STANDARD_DEVIATION 14.4 | 40.9 years STANDARD_DEVIATION 14.4 |
| Race/Ethnicity, Customized Asian | 20 Participants | 11 Participants | 9 Participants | 3 Participants | 9 Participants | 8 Participants | 8 Participants | 7 Participants | 6 Participants | 5 Participants | 86 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 80 Participants | 20 Participants | 24 Participants | 29 Participants | 22 Participants | 23 Participants | 24 Participants | 25 Participants | 24 Participants | 28 Participants | 299 Participants |
| Randomization Stratification Closed with reamed IM nail | 88 Participants | 30 Participants | 30 Participants | 29 Participants | 29 Participants | 29 Participants | 29 Participants | 29 Participants | 28 Participants | 29 Participants | 350 Participants |
| Randomization Stratification Gustilo type I/II open with reamed IM nail | 10 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 42 Participants |
| Randomization Stratification Gustilo type I/II open with unreamed IM nail | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Female | 29 Participants | 7 Participants | 10 Participants | 8 Participants | 8 Participants | 11 Participants | 11 Participants | 5 Participants | 13 Participants | 12 Participants | 114 Participants |
| Sex: Female, Male Male | 74 Participants | 27 Participants | 24 Participants | 25 Participants | 25 Participants | 22 Participants | 22 Participants | 28 Participants | 18 Participants | 23 Participants | 288 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 38 / 100 | 9 / 34 | 17 / 34 | 12 / 32 | 16 / 33 | 7 / 32 | 9 / 31 | 10 / 32 | 9 / 30 | 6 / 35 |
| serious Total, serious adverse events | 10 / 100 | 4 / 34 | 2 / 34 | 3 / 32 | 3 / 33 | 4 / 32 | 2 / 31 | 3 / 32 | 3 / 30 | 0 / 35 |
Outcome results
Primary
Time to Radiographic Healing
Time to radiographic healing was defined as the time from intramedullary (IM) nailing to the first occurrence of bridging of 3 out of 4 cortices. Radiographic fracture healing was determined by a panel of independent reviewers (orthopedic/trauma surgeons and radiologists) blinded to treatment. The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate.
Time frame: 52 weeks
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Radiographic Healing | 16.4 weeks |
| Romosozumab 70 mg: 2 Doses | Time to Radiographic Healing | 18.6 weeks |
| Romosozumab 70 mg: 3 Doses | Time to Radiographic Healing | 18.3 weeks |
| Romosozumab 70 mg: 4 Doses | Time to Radiographic Healing | 18.2 weeks |
| Romosozumab 140 mg: 2 Doses | Time to Radiographic Healing | 17.8 weeks |
| Romosozumab 140 mg: 3 Doses | Time to Radiographic Healing | 18.1 weeks |
| Romosozumab 140 mg: 4 Doses | Time to Radiographic Healing | 17.0 weeks |
| Romosozumab 210 mg: 2 Doses | Time to Radiographic Healing | 14.4 weeks |
| Romosozumab 210 mg: 3 Doses | Time to Radiographic Healing | 15.4 weeks |
| Romosozumab 210 mg: 4 Doses | Time to Radiographic Healing | 16.4 weeks |
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.359895% CI: [0.53, 1.26]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.654495% CI: [0.59, 1.39]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.995895% CI: [0.64, 1.58]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.627695% CI: [0.59, 1.37]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.881995% CI: [0.63, 1.49]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.719795% CI: [0.6, 1.42]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.620495% CI: [0.73, 1.7]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.477995% CI: [0.75, 1.84]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.995295% CI: [0.65, 1.53]Cox proportional hazard model
Secondary
Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain
The Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2, is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning domain includes 10 questions that assess limitations in physical activities because of health problems. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. The range of SF-36 physical functioning is 14.94 - 57.03. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement in physical functioning.
Time frame: Week 8 and weeks 12, 16, 20, 24, 36, and 52
Population: Participants who received at least 1 dose of study drug and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 5.77 units on a scale | Standard Deviation 9.9 |
| Placebo | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 13.20 units on a scale | Standard Deviation 12.25 |
| Placebo | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 20.74 units on a scale | Standard Deviation 11.96 |
| Placebo | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 19.57 units on a scale | Standard Deviation 11.6 |
| Placebo | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 9.64 units on a scale | Standard Deviation 10.36 |
| Placebo | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 15.87 units on a scale | Standard Deviation 11.55 |
| Romosozumab 70 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 9.83 units on a scale | Standard Deviation 7.24 |
| Romosozumab 70 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 20.96 units on a scale | Standard Deviation 11.68 |
| Romosozumab 70 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 14.53 units on a scale | Standard Deviation 9.69 |
| Romosozumab 70 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 6.31 units on a scale | Standard Deviation 6.84 |
| Romosozumab 70 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 15.07 units on a scale | Standard Deviation 9.31 |
| Romosozumab 70 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 23.47 units on a scale | Standard Deviation 11.55 |
| Romosozumab 70 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 5.67 units on a scale | Standard Deviation 8.6 |
| Romosozumab 70 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 13.63 units on a scale | Standard Deviation 19.04 |
| Romosozumab 70 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 9.19 units on a scale | Standard Deviation 11.3 |
| Romosozumab 70 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 11.48 units on a scale | Standard Deviation 17.84 |
| Romosozumab 70 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 10.34 units on a scale | Standard Deviation 13.31 |
| Romosozumab 70 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 10.45 units on a scale | Standard Deviation 11.66 |
| Romosozumab 70 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 15.90 units on a scale | Standard Deviation 11.26 |
| Romosozumab 70 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 13.50 units on a scale | Standard Deviation 12.02 |
| Romosozumab 70 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 19.02 units on a scale | Standard Deviation 10.8 |
| Romosozumab 70 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 5.04 units on a scale | Standard Deviation 9.01 |
| Romosozumab 70 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 9.28 units on a scale | Standard Deviation 11.14 |
| Romosozumab 70 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 17.23 units on a scale | Standard Deviation 10.15 |
| Romosozumab 140 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 8.89 units on a scale | Standard Deviation 10.71 |
| Romosozumab 140 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 4.28 units on a scale | Standard Deviation 8.22 |
| Romosozumab 140 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 12.13 units on a scale | Standard Deviation 10.88 |
| Romosozumab 140 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 14.57 units on a scale | Standard Deviation 10.34 |
| Romosozumab 140 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 17.61 units on a scale | Standard Deviation 11.03 |
| Romosozumab 140 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 19.63 units on a scale | Standard Deviation 12.17 |
| Romosozumab 140 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 14.77 units on a scale | Standard Deviation 13.52 |
| Romosozumab 140 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 11.18 units on a scale | Standard Deviation 9.23 |
| Romosozumab 140 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 24.80 units on a scale | Standard Deviation 11.24 |
| Romosozumab 140 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 7.08 units on a scale | Standard Deviation 8.06 |
| Romosozumab 140 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 19.43 units on a scale | Standard Deviation 12.83 |
| Romosozumab 140 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 16.84 units on a scale | Standard Deviation 12.7 |
| Romosozumab 140 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 12.44 units on a scale | Standard Deviation 11.97 |
| Romosozumab 140 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 11.79 units on a scale | Standard Deviation 17.64 |
| Romosozumab 140 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 8.78 units on a scale | Standard Deviation 11.34 |
| Romosozumab 140 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 15.70 units on a scale | Standard Deviation 19.03 |
| Romosozumab 140 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 3.63 units on a scale | Standard Deviation 9.3 |
| Romosozumab 140 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 17.19 units on a scale | Standard Deviation 15.51 |
| Romosozumab 210 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 13.05 units on a scale | Standard Deviation 10.99 |
| Romosozumab 210 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 15.50 units on a scale | Standard Deviation 13.17 |
| Romosozumab 210 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 12.61 units on a scale | Standard Deviation 10.88 |
| Romosozumab 210 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 15.01 units on a scale | Standard Deviation 11.23 |
| Romosozumab 210 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 3.65 units on a scale | Standard Deviation 9.06 |
| Romosozumab 210 mg: 2 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 9.23 units on a scale | Standard Deviation 9.59 |
| Romosozumab 210 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 7.33 units on a scale | Standard Deviation 7.99 |
| Romosozumab 210 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 12.50 units on a scale | Standard Deviation 10.76 |
| Romosozumab 210 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 18.29 units on a scale | Standard Deviation 14.94 |
| Romosozumab 210 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 9.50 units on a scale | Standard Deviation 9.01 |
| Romosozumab 210 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 13.05 units on a scale | Standard Deviation 10.25 |
| Romosozumab 210 mg: 3 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 17.47 units on a scale | Standard Deviation 14.34 |
| Romosozumab 210 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 24 | 12.38 units on a scale | Standard Deviation 14.04 |
| Romosozumab 210 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 36 | 15.22 units on a scale | Standard Deviation 15.2 |
| Romosozumab 210 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 20 | 11.05 units on a scale | Standard Deviation 11.56 |
| Romosozumab 210 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 52 | 15.44 units on a scale | Standard Deviation 17.15 |
| Romosozumab 210 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 12 | 5.64 units on a scale | Standard Deviation 6.67 |
| Romosozumab 210 mg: 4 Doses | Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain | Week 16 | 9.01 units on a scale | Standard Deviation 10.41 |
Secondary
Number of Participants With Unplanned Revision Surgeries
Time frame: 52 weeks
Population: Participants who received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Unplanned Revision Surgeries | 8 Participants |
| Romosozumab 70 mg: 2 Doses | Number of Participants With Unplanned Revision Surgeries | 1 Participants |
| Romosozumab 70 mg: 3 Doses | Number of Participants With Unplanned Revision Surgeries | 3 Participants |
| Romosozumab 70 mg: 4 Doses | Number of Participants With Unplanned Revision Surgeries | 3 Participants |
| Romosozumab 140 mg: 2 Doses | Number of Participants With Unplanned Revision Surgeries | 1 Participants |
| Romosozumab 140 mg: 3 Doses | Number of Participants With Unplanned Revision Surgeries | 0 Participants |
| Romosozumab 140 mg: 4 Doses | Number of Participants With Unplanned Revision Surgeries | 0 Participants |
| Romosozumab 210 mg: 2 Doses | Number of Participants With Unplanned Revision Surgeries | 0 Participants |
| Romosozumab 210 mg: 3 Doses | Number of Participants With Unplanned Revision Surgeries | 1 Participants |
| Romosozumab 210 mg: 4 Doses | Number of Participants With Unplanned Revision Surgeries | 1 Participants |
Secondary
Time to Clinical Healing
Time to clinical healing was defined as the time from the IM nailing surgery date to the first date that both the score for ability to bear weight on the fractured limb and the score for absence of pain at the fracture site were equal to 6. The score for the ability to bear weight on the fractured limb was based on the ability to stand on affected leg without assistive device and the ability to walk without assistive device. The score ranges from 0 (unable to bear full body weight on the fractured limb) to 6 (able to bear full body weight on the fractured limb). Absence of pain at the fracture site was based on the absence of pain at the fracture site when applying direct pressure to the fracture site and applying a stress to the fracture site. The score ranges from 0 (pain without palpation at fracture site) to 6 (total absence of pain at fracture site). Time to clinical healing was estimated using CIF; unplanned revision surgery was considered a competing risk in CIF estimate.
Time frame: 52 weeks
Population: Participants who received at least 1 dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Clinical Healing | 18.4 weeks |
| Romosozumab 70 mg: 2 Doses | Time to Clinical Healing | 21.4 weeks |
| Romosozumab 70 mg: 3 Doses | Time to Clinical Healing | 18.3 weeks |
| Romosozumab 70 mg: 4 Doses | Time to Clinical Healing | 17.1 weeks |
| Romosozumab 140 mg: 2 Doses | Time to Clinical Healing | 20.8 weeks |
| Romosozumab 140 mg: 3 Doses | Time to Clinical Healing | 22.3 weeks |
| Romosozumab 140 mg: 4 Doses | Time to Clinical Healing | 15.0 weeks |
| Romosozumab 210 mg: 2 Doses | Time to Clinical Healing | 16.3 weeks |
| Romosozumab 210 mg: 3 Doses | Time to Clinical Healing | 14.6 weeks |
| Romosozumab 210 mg: 4 Doses | Time to Clinical Healing | 17.6 weeks |
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.171395% CI: [0.47, 1.14]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.995895% CI: [0.65, 1.53]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.29595% CI: [0.81, 1.97]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.084495% CI: [0.44, 1.05]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.322595% CI: [0.52, 1.24]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.475495% CI: [0.76, 1.81]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.557895% CI: [0.74, 1.75]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.186495% CI: [0.87, 2.07]Cox proportional hazard model
Comparison: The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.p-value: 0.848895% CI: [0.68, 1.59]Cox proportional hazard model