Osteoporosis
Conditions
Keywords
AMG 785, bone mineral density, alendronate
Brief summary
The purpose of this study is to estimate the percent change from baseline in lumbar spine bone mineral density (BMD) following multiple-dose administrations of romosozumab in postmenopausal women with low BMD previously treated with alendronate.
Interventions
DRUGRomosozumab
Administered by subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women, defined as no vaginal bleeding or spotting for ≥ 12 months * Low bone mineral density at screening \[defined by a bone mineral density (BMD) T-score ≤ -2.0 and ≥ -4.0 at the lumbar spine (L1 to L4; or BMD T-score of evaluable vertebrae), total hip, or femoral neck\] * Currently taking alendronate (70 mg weekly or equivalent) exclusively for ≥ 1 year with verbal agreement that the subject has taken ≥ 80% of their doses with good tolerance
Exclusion criteria
* History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis after age 50; or recent bone fracture within 6 months prior to screening * History of metabolic or bone disease such as Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome * Vitamin D deficiency (defined as 25-OH-VitD levels \< 20 ng/mL)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine | Baseline and day 85 | Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and analyzed by a central imaging lab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Bone Mineral Density (BMD) at the Total Hip | Baseline and day 85 | Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab. |
| Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Baseline and days 4, 15, 29, 43, 57, 71, and 85 | — |
| Percent Change From Baseline in Serum C-telopeptide (sCTX) | Baseline and days 4, 15, 29, 43, 57, 71, and 85 | — |
| Percent Change From Baseline in Bone Mineral Density (BMD) at the Femoral Neck | Baseline and day 85 | Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab. |
| Number of Participants Who Developed Anti-romosozumab Antibodies | Baseline and days 29, 57, and 85 | Two validated assays were used to detect the presence of anti-romosozumab antibodies. An electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Samples testing positive in the immunoassay were further tested in a competitive binding bioassay for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity, the participant was defined as positive for neutralizing antibodies. Participants who developed anti-romosozumab antibodies were those with a negative result at baseline and a positive result at any time postbaseline. |
| Mean Serum Concentration of Romosozumab | Days 4, 15, 29, 43, 57, 71 and 85 | — |
| Number of Participants With Adverse Events | From first dose of study drug up to day 85 | An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events. A treatment-related adverse event (TRAE) was an adverse event assessed by the investigator as possibly related to the investigational product, indicated by a yes response to the question: Is there a reasonable possibility that the event may have been caused by the investigational product? A serious adverse event was defined as an adverse event that met at least 1 of the following serious criteria: * fatal, * life-threatening, * required in-patient hospitalization or prolongation of existing hospitalization, * resulted in persistent or significant disability/incapacity, * congenital anomaly/birth defect, and/or * other medically important serious event. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 8 centers in the United States. The first participant enrolled on 30 March 2012 and the last participant enrolled on 21 August 2012.
Participants by arm
| Arm | Count |
|---|---|
| Romosozumab 140 mg Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months. | 30 |
| Romosozumab 210 mg Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months. | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Romosozumab 210 mg | Total | Romosozumab 140 mg |
|---|---|---|---|
| Age, Continuous | 66.7 years STANDARD_DEVIATION 8.3 | 66.1 years STANDARD_DEVIATION 7.8 | 65.6 years STANDARD_DEVIATION 7.5 |
| Age, Customized < 65 years | 15 Participants | 29 Participants | 14 Participants |
| Age, Customized ≥ 65 years | 15 Participants | 31 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 26 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 34 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 7 Participants | 5 Participants |
| Race/Ethnicity, Customized Black (or African American) | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 50 Participants | 25 Participants |
| Sex: Female, Male Female | 30 Participants | 60 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 30 | 6 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine
Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and analyzed by a central imaging lab.
Time frame: Baseline and day 85
Population: All participants who received study drug and with non-missing baseline and day 85 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romosozumab 140 mg | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine | 2.13 percent change | Standard Error 0.64 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine | 2.08 percent change | Standard Error 0.63 |
p-value: 0.00290% CI: [1.05, 3.2]ANOVA
p-value: 0.00290% CI: [1.02, 3.14]ANOVA
Secondary
Mean Serum Concentration of Romosozumab
Time frame: Days 4, 15, 29, 43, 57, 71 and 85
Population: All participants who received study drug with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Romosozumab 140 mg | Mean Serum Concentration of Romosozumab | Day 29 | 3890 ng/mL | Standard Deviation 2000 |
| Romosozumab 140 mg | Mean Serum Concentration of Romosozumab | Day 57 | 5490 ng/mL | Standard Deviation 2600 |
| Romosozumab 140 mg | Mean Serum Concentration of Romosozumab | Day 15 | 10500 ng/mL | Standard Deviation 3540 |
| Romosozumab 140 mg | Mean Serum Concentration of Romosozumab | Day 71 | 13700 ng/mL | Standard Deviation 5000 |
| Romosozumab 140 mg | Mean Serum Concentration of Romosozumab | Day 43 | 14300 ng/mL | Standard Deviation 4280 |
| Romosozumab 140 mg | Mean Serum Concentration of Romosozumab | Day 85 | 5350 ng/mL | Standard Deviation 3190 |
| Romosozumab 140 mg | Mean Serum Concentration of Romosozumab | Day 4 | 15000 ng/mL | Standard Deviation 6350 |
| Romosozumab 210 mg | Mean Serum Concentration of Romosozumab | Day 85 | 11600 ng/mL | Standard Deviation 6850 |
| Romosozumab 210 mg | Mean Serum Concentration of Romosozumab | Day 4 | 23200 ng/mL | Standard Deviation 9730 |
| Romosozumab 210 mg | Mean Serum Concentration of Romosozumab | Day 15 | 18500 ng/mL | Standard Deviation 6640 |
| Romosozumab 210 mg | Mean Serum Concentration of Romosozumab | Day 29 | 8200 ng/mL | Standard Deviation 4470 |
| Romosozumab 210 mg | Mean Serum Concentration of Romosozumab | Day 43 | 22800 ng/mL | Standard Deviation 9390 |
| Romosozumab 210 mg | Mean Serum Concentration of Romosozumab | Day 57 | 10700 ng/mL | Standard Deviation 6380 |
| Romosozumab 210 mg | Mean Serum Concentration of Romosozumab | Day 71 | 22700 ng/mL | Standard Deviation 10500 |
Secondary
Number of Participants Who Developed Anti-romosozumab Antibodies
Two validated assays were used to detect the presence of anti-romosozumab antibodies. An electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Samples testing positive in the immunoassay were further tested in a competitive binding bioassay for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity, the participant was defined as positive for neutralizing antibodies. Participants who developed anti-romosozumab antibodies were those with a negative result at baseline and a positive result at any time postbaseline.
Time frame: Baseline and days 29, 57, and 85
Population: All participants who received study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Romosozumab 140 mg | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 2 Participants |
| Romosozumab 140 mg | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Romosozumab 210 mg | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 2 Participants |
| Romosozumab 210 mg | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 Participants |
Secondary
Number of Participants With Adverse Events
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events. A treatment-related adverse event (TRAE) was an adverse event assessed by the investigator as possibly related to the investigational product, indicated by a yes response to the question: Is there a reasonable possibility that the event may have been caused by the investigational product? A serious adverse event was defined as an adverse event that met at least 1 of the following serious criteria: * fatal, * life-threatening, * required in-patient hospitalization or prolongation of existing hospitalization, * resulted in persistent or significant disability/incapacity, * congenital anomaly/birth defect, and/or * other medically important serious event.
Time frame: From first dose of study drug up to day 85
Population: All participants who received study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Romosozumab 140 mg | Number of Participants With Adverse Events | All adverse events | 14 Participants |
| Romosozumab 140 mg | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Romosozumab 140 mg | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Romosozumab 140 mg | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Romosozumab 140 mg | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Romosozumab 140 mg | Number of Participants With Adverse Events | Treatment-related adverse events | 3 Participants |
| Romosozumab 140 mg | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Romosozumab 140 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Romosozumab 140 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Romosozumab 140 mg | Number of Participants With Adverse Events | Treatment-related fatal adverse events | 0 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | All adverse events | 15 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | Treatment-related adverse events | 4 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | Treatment-related fatal adverse events | 0 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | AE leading to discontinuation of study drug | 0 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | AE leading to discontinuation from study | 0 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 0 Participants |
| Romosozumab 210 mg | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
Secondary
Percent Change From Baseline in Bone Mineral Density (BMD) at the Femoral Neck
Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.
Time frame: Baseline and day 85
Population: All participants who received study drug and with non-missing baseline and day 85 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romosozumab 140 mg | Percent Change From Baseline in Bone Mineral Density (BMD) at the Femoral Neck | 2.06 percent change | Standard Error 0.59 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Mineral Density (BMD) at the Femoral Neck | 1.92 percent change | Standard Error 0.58 |
p-value: <0.00190% CI: [1.07, 3.05]ANOVA
p-value: 0.00290% CI: [0.95, 2.89]ANOVA
Secondary
Percent Change From Baseline in Bone Mineral Density (BMD) at the Total Hip
Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.
Time frame: Baseline and day 85
Population: All participants who received study drug and with non-missing baseline and day 85 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romosozumab 140 mg | Percent Change From Baseline in Bone Mineral Density (BMD) at the Total Hip | 1.38 percent change | Standard Error 0.34 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Mineral Density (BMD) at the Total Hip | 1.40 percent change | Standard Error 0.34 |
p-value: <0.00190% CI: [0.81, 1.95]ANOVA
p-value: <0.00190% CI: [0.84, 1.96]ANOVA
Secondary
Percent Change From Baseline in Serum C-telopeptide (sCTX)
Time frame: Baseline and days 4, 15, 29, 43, 57, 71, and 85
Population: All participants who received study drug and with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Romosozumab 140 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 29 | 3.1008 percent change | Standard Error 8.6448 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 57 | 25.7433 percent change | Standard Error 8.744 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 15 | -28.9365 percent change | Standard Error 4.6974 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 71 | 28.4465 percent change | Standard Error 11.7345 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 43 | 3.4511 percent change | Standard Error 8.9913 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 85 | 54.0549 percent change | Standard Error 14.214 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 4 | -28.2149 percent change | Standard Error 3.9352 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 85 | 61.1734 percent change | Standard Error 13.9874 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 4 | -14.8099 percent change | Standard Error 4.6844 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 15 | -22.2800 percent change | Standard Error 5.1854 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 29 | -1.8188 percent change | Standard Error 7.4121 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 43 | 11.0131 percent change | Standard Error 10.0244 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 57 | 35.7697 percent change | Standard Error 13.5346 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum C-telopeptide (sCTX) | Day 71 | 44.3802 percent change | Standard Error 13.7159 |
Secondary
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)
Time frame: Baseline and days 4, 15, 29, 43, 57, 71, and 85
Population: All participants who received study drug and with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Romosozumab 140 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 29 | 128.3936 percent change | Standard Error 17.7834 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 57 | 99.3682 percent change | Standard Error 14.9155 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 15 | 140.9970 percent change | Standard Error 15.1975 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 71 | 127.4051 percent change | Standard Error 14.8572 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 43 | 164.1654 percent change | Standard Error 17.7832 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 85 | 64.9103 percent change | Standard Error 10.5005 |
| Romosozumab 140 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 4 | 22.1263 percent change | Standard Error 3.3852 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 85 | 142.5601 percent change | Standard Error 20.3233 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 4 | 30.4935 percent change | Standard Error 4.995 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 15 | 218.4994 percent change | Standard Error 22.6148 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 29 | 221.9954 percent change | Standard Error 23.3718 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 43 | 251.0495 percent change | Standard Error 23.4572 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 57 | 168.7689 percent change | Standard Error 17.1565 |
| Romosozumab 210 mg | Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) | Day 71 | 205.2619 percent change | Standard Error 23.5171 |