Postmenopausal Osteoporosis
Conditions
Keywords
Postmenopausal Osteoporosis
Brief summary
The purpose of this study is to compare 2 formulations of romosozumab (AMG 785) on bone mineral density (BMD) in postmenopausal women with osteoporosis.
Detailed description
Upon confirmation of eligibility, participants were randomized in a 22:5:22:5 ratio to the following treatment groups: * Romosozumab 90 mg/mL * Placebo 90 mg/mL * Romosozumab 70 mg/mL * Placebo 70 mg/mL After completing a 6-month treatment period, participants entered a 3-month follow-up period with an end of study (EOS) at month 9. For the analysis of efficacy endpoints, the 2 placebo groups were combined into a single placebo group. For safety analyses, the data for placebo were presented separately for each group.
Interventions
DRUGRomosozumab 90 mg/mL
Administered as 2 SC injections of a 90 mg/mL concentration in a 1.17 mL crystal zenith resin prefilled syringe (PFS).
DRUGPlacebo 90 mg/mL
Placebo administered as 2 SC injections with the 1.17 mL crystal zenith resin PFS.
DRUGRomosozumab 70 mg/mL
Administered as 3 SC injections of a 70 mg/mL concentration in a 1.0 mL glass PFS.
DRUGPlacebo 70 mg/mL
Placebo administered as 3 SC injections with the 1.0 mL glass PFS.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Postmenopausal women with osteoporosis at high risk for fracture defined as * BMD T-score ≤ -2.50 at the lumbar spine, total hip, or femoral neck AND * a history of fragility fracture or at least 2 other risk factors
Exclusion criteria
* BMD T score \< -3.50 at the total hip or femoral neck. * History of hip fracture. * History of metabolic or bone disease (except osteoporosis). * Use of agents affecting bone metabolism. * Vitamin D insufficiency. * History of solid organ or bone marrow transplants. * Hyper- or hypocalcemia. * Hyper- or hypothyroidism. * Hyper- or hypoparathyroidism.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine | Baseline and month 6 | Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Hip BMD | Baseline and month 6 | Total hip BMD was measured using DXA. The analysis was based on an ANCOVA model adjusted for treatment and baseline total hip BMD T-score. |
| Percent Change From Baseline in Femoral Neck BMD | Baseline and month 6 | Femoral neck BMD was measured using DXA. The analysis was based on an ANCOVA model adjusted for treatment and baseline femoral neck BMD T-score. |
| Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Baseline, month 1, month 3, and month 6 | — |
| Percent Change From Baseline in Serum C-Telopeptide (CTX) | Baseline, month 1, month 3, and month 6 | — |
Countries
Czechia, Poland, United States
Participant flow
Recruitment details
This study was conducted at 11 centers: 7 in Poland, 2 in the Czech Republic, and 2 in the United States. The first participant enrolled on 03 December 2013 and the last participant enrolled on 07 March 2014.
Pre-assignment details
Eligible participants were randomized in a 22:5:22:5 ratio to receive * romosozumab 90 mg/mL * placebo 90 mg/mL * romosozumab 70 mg/mL * placebo 70 mg/mL For efficacy analyses the 2 placebo groups were combined, for safety analyses the data were reported separately.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo (either administered as 2 subcutaneous (SC) injections of 1.17 mL or 3 SC injections of 1.0 mL) every month for 6 months. | 53 |
| Romosozumab 70 mg/mL Participants received 210 mg romosozumab monthly, administered as 3 subcutaneous 1 mL injections of a 70 mg/mL solution, for 6 months. | 118 |
| Romosozumab 90 mg/mL Participants received 210 mg romosozumab monthly, administered as 2 subcutaneous 1.17 mL injections of a 90 mg/mL solution, for 6 months. | 123 |
| Total | 294 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
| Overall Study | Protocol-specified Criteria | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 5 | 5 |
Baseline characteristics
| Characteristic | Total | Romosozumab 90 mg/mL | Placebo | Romosozumab 70 mg/mL |
|---|---|---|---|---|
| Age, Continuous | 67.7 years STANDARD_DEVIATION 7.5 | 67.7 years STANDARD_DEVIATION 7.6 | 68.4 years STANDARD_DEVIATION 8 | 67.4 years STANDARD_DEVIATION 7.1 |
| Age, Customized < 65 years | 115 Participants | 46 Participants | 23 Participants | 46 Participants |
| Age, Customized ≥ 65 years | 179 Participants | 77 Participants | 30 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 9 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 277 Participants | 114 Participants | 51 Participants | 112 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Femoral Neck BMD T-score | -2.118 T-score STANDARD_DEVIATION 0.595 | -2.018 T-score STANDARD_DEVIATION 0.593 | -2.304 T-score STANDARD_DEVIATION 0.517 | -2.139 T-score STANDARD_DEVIATION 0.611 |
| Lumbar Spine Bone Mineral Density (BMD) T-score | -2.970 T-score STANDARD_DEVIATION 0.871 | -3.029 T-score STANDARD_DEVIATION 0.687 | -2.842 T-score STANDARD_DEVIATION 1.033 | -2.965 T-score STANDARD_DEVIATION 0.96 |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black (or African American) | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 291 Participants | 123 Participants | 53 Participants | 115 Participants |
| Serum Procollagen Type 1 N-telopeptide (P1NP) | 51.0 μg/L | 50.0 μg/L | 49.0 μg/L | 53.0 μg/L |
| Serum Type 1 Collagen C-telopeptide (CTX) | 426.0 ng/L | 402.0 ng/L | 426.5 ng/L | 440.0 ng/L |
| Sex: Female, Male Female | 294 Participants | 123 Participants | 53 Participants | 118 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Total Hip BMD T-score | -1.866 T-score STANDARD_DEVIATION 0.66 | -1.828 T-score STANDARD_DEVIATION 0.649 | -2.057 T-score STANDARD_DEVIATION 0.634 | -1.819 T-score STANDARD_DEVIATION 0.673 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 26 | 5 / 26 | 24 / 119 | 38 / 123 |
| serious Total, serious adverse events | 4 / 26 | 2 / 26 | 7 / 119 | 3 / 123 |
Outcome results
Primary
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine
Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).
Time frame: Baseline and month 6
Population: All randomized participants who had a baseline and a month 6 lumbar spine DXA BMD measurement
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine | 0.8 percent change |
| Romosozumab 70 mg/mL | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine | 9.6 percent change |
| Romosozumab 90 mg/mL | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine | 9.2 percent change |
Comparison: The primary hypothesis was that the mean percent change from baseline in lumbar spine BMD at month 6 in participants receiving romosozumab 210 mg QM using the 90 mg/mL concentration would not be inferior to that in participants receiving romosozumab 210 mg QM using the 70 mg/mL concentration.95% CI: [-1.5, 0.7]
Secondary
Percent Change From Baseline in Femoral Neck BMD
Femoral neck BMD was measured using DXA. The analysis was based on an ANCOVA model adjusted for treatment and baseline femoral neck BMD T-score.
Time frame: Baseline and month 6
Population: All randomized participants who had a baseline and month 6 femoral neck DXA BMD measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Femoral Neck BMD | -0.5 percent change |
| Romosozumab 70 mg/mL | Percent Change From Baseline in Femoral Neck BMD | 3.1 percent change |
| Romosozumab 90 mg/mL | Percent Change From Baseline in Femoral Neck BMD | 2.6 percent change |
Secondary
Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP)
Time frame: Baseline, month 1, month 3, and month 6
Population: All randomized participants who had a baseline and at least one postbaseline measurement for P1NP, and with available data at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Month 6 | -12.500 percent change |
| Placebo | Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Month 3 | -9.601 percent change |
| Placebo | Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Month 1 | 2.000 percent change |
| Romosozumab 70 mg/mL | Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Month 6 | -2.885 percent change |
| Romosozumab 70 mg/mL | Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Month 3 | 23.960 percent change |
| Romosozumab 70 mg/mL | Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Month 1 | 96.296 percent change |
| Romosozumab 90 mg/mL | Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Month 6 | -3.604 percent change |
| Romosozumab 90 mg/mL | Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Month 1 | 97.435 percent change |
| Romosozumab 90 mg/mL | Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP) | Month 3 | 16.216 percent change |
Secondary
Percent Change From Baseline in Serum C-Telopeptide (CTX)
Time frame: Baseline, month 1, month 3, and month 6
Population: All randomized participants who had a baseline and at least one postbaseline measurement for CTX and with available data at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Serum C-Telopeptide (CTX) | Month 3 | -5.687 percent change |
| Placebo | Percent Change From Baseline in Serum C-Telopeptide (CTX) | Month 1 | 0.282 percent change |
| Placebo | Percent Change From Baseline in Serum C-Telopeptide (CTX) | Month 6 | -8.120 percent change |
| Romosozumab 70 mg/mL | Percent Change From Baseline in Serum C-Telopeptide (CTX) | Month 3 | -11.219 percent change |
| Romosozumab 70 mg/mL | Percent Change From Baseline in Serum C-Telopeptide (CTX) | Month 1 | -23.158 percent change |
| Romosozumab 70 mg/mL | Percent Change From Baseline in Serum C-Telopeptide (CTX) | Month 6 | -25.780 percent change |
| Romosozumab 90 mg/mL | Percent Change From Baseline in Serum C-Telopeptide (CTX) | Month 1 | -21.456 percent change |
| Romosozumab 90 mg/mL | Percent Change From Baseline in Serum C-Telopeptide (CTX) | Month 6 | -17.305 percent change |
| Romosozumab 90 mg/mL | Percent Change From Baseline in Serum C-Telopeptide (CTX) | Month 3 | -5.473 percent change |
Secondary
Percent Change From Baseline in Total Hip BMD
Total hip BMD was measured using DXA. The analysis was based on an ANCOVA model adjusted for treatment and baseline total hip BMD T-score.
Time frame: Baseline and month 6
Population: All randomized participants who had a baseline and month 6 hip DXA BMD measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Total Hip BMD | -0.0 percent change |
| Romosozumab 70 mg/mL | Percent Change From Baseline in Total Hip BMD | 3.9 percent change |
| Romosozumab 90 mg/mL | Percent Change From Baseline in Total Hip BMD | 3.4 percent change |