Post-Menopausal Osteoporosis
Conditions
Keywords
Post-Menopausal osteoporosis
Brief summary
To evaluate the noninferiority of a 6-month treatment with 210 mg romosozumab at 90 mg/mL administered subcutaneously (SC) once a month (QM) in postmenopausal women with osteoporosis either by healthcare provider (HCP) administration with prefilled syringe (PFS) or by subject self-administration with autoinjector/pen (AI/Pen)
Interventions
DRUGromosozumab HCP administration with PFS
210 mg romosozumab SC QM by HCP administration with 2 PFS
DEVICEromosozumab self-administration with AI/Pen
210 mg romosozumab SC QM by self-administration with 2 AI/Pens
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study; blinding procedures are not applicable.
Intervention model description
After signing the informed consent form (ICF), subjects will undergo the following periods: * Screening period (35 days) to complete eligibility assessments * Open-label treatment period (6 months) * Follow-up period (3 months) During the open-label treatment period, subjects will be randomized to receive romosozumab either via HCP administration with PFS or via self-administration withAI/Pen. During the follow-up period, subjects will be followed for an additional 3 months to ensure appropriate follow-up for anti-romosozumab antibody formation and adverse events. The primary analysis will be performed after all subjects have had the opportunity to complete the Month 6 visit. The final analysis will be performed after all subjects have had the opportunity to complete the Month 9 visit.
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent/assent prior to initiation of any studyspecific activities/procedures, or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent. * Postmenopausal female (postmenopausal status is defined as no vaginal bleeding or spotting for 12 consecutive months prior to screening) -≥ 55 to ≤ 90 years of age at the time of informed consent * Ambulatory * BMD T-score ≤ -2.50 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans -Subject has at least 2 vertebrae in the L1-L4 region evaluable by DXA, as assessed by the principal investigator or designee * Subject has at least 1 hip evaluable by DXA, as assessed by the principal investigator or designee * Subject has history of fragility (ie, osteoporosis-related fracture) or subject meets at least 2 of the following clinical risk factors for fracture * ≥ 70 years of age at the time of informed consent * BMD T-score ≤ -3.00 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans * current smoker * consumption of ≥ 3 glasses of alcohol a day * parental history of fragility (ie, osteoporosis-related) fracture * body weight ≤ 125 pounds/56 kilogram * Ability to follow and understand instructions and the ability to self-inject, per investigator judgement
Exclusion criteria
* History of osteonecrosis of the jaw and/or atypical femoral fracture * History of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as sclerosteosis, Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome * Subject with reported history of hearing loss associated with cranial nerve VIII compression due to excessive bone growth (eg, as seen in conditions such as Paget's disease, sclerosteosis and osteopetrosis) * Vitamin D insufficiency \[defined as serum 25 (OH) vitamin D levels \< 20 ng/mL\], as determined by the central laboratory. Vitamin D repletion will be permitted a nd subjects may be rescreened * Current hyperthyroidism (unless well controlled on stable antithyroid therapy) by subject report or by chart review, per principal investigator evaluation * Current clinical hypothyroidism (unless well controlled on stable thyroid replacement therapy) by subject report or by chart review, per principal investigator evaluation normal range, per subject medical history. Uncontrolled hyperparathyroidism is defined as: parathyroid hormone (PTH) outside the normal range in subjects with concurrent hypercalcemia; or PTH values \> 20% above the upper limit of normal (ULN) in normocalcemic subjects. * Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory. Serum calcium levels may be retested once in case of an elevated serum calcium level within 1.1x the ULN as assessed by the central laboratory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lumbar Spine BMD at Month 6 | Baseline, Month 6 | Percent change from baseline in BMD at the lumbar spine as measured by dual-energy x-ray absorptiometry (DXA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Hip BMD at Month 6 | Baseline, Month 6 | Percent change from baseline in BMD for total hip as measured by DXA. |
| Percent Change From Baseline in Femoral Neck BMD at Month 6 | Baseline, Month 6 | Percent change from baseline in BMD at femoral neck as measured by DXA. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | up to Month 9 (-7/+3 days) | AE: any untoward medical occurrence irrespective of a causal relationship with the study treatment. SAE: any untoward medical occurrence that meets at least 1 of the following criteria: results in death; is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important serious event. Adverse device effect: any AE related to the use of a combination product or medical device. TEAEs are those AEs occurring after first dose of study drug. |
| Number of Participants Developing Anti-Romosozumab Antibodies | up to Month 9 (-7/+3 days) | Participants with a negative or no result at baseline (BL) developing anti-romosozumab antibodies postbaseline, including those who were binding antibody-positive or neutralizing antibody-positive postbaseline. 'Transient' positive results are those with a negative result at the participant's last time point tested within the study period. |
Countries
Poland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 36 centers in Poland, United Kingdom, and United States.
Pre-assignment details
Participants were randomized in a 1:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| Romosozumab 210 mg QM: PFS During the open-label treatment period, participants received 210 mg romosozumab SC QM by HCP administration with PFS. | 141 |
| Romosozumab 210 mg QM: AI/Pen During the open-label treatment period, participants received 210 mg romosozumab SC QM by self-administration with AI/pen. | 142 |
| Total | 283 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Withdrawal by Subject | 14 | 9 |
Baseline characteristics
| Characteristic | Total | Romosozumab 210 mg QM: AI/Pen | Romosozumab 210 mg QM: PFS |
|---|---|---|---|
| Age, Continuous | 69.9 years STANDARD_DEVIATION 7.8 | 69.5 years STANDARD_DEVIATION 8.4 | 70.3 years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 279 Participants | 141 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Femoral Neck BMD T-Score | -2.52 T-score STANDARD_DEVIATION 0.64 | -2.49 T-score STANDARD_DEVIATION 0.65 | -2.54 T-score STANDARD_DEVIATION 0.63 |
| Lumbar Spine Bone Mineral Density (BMD) T-Score | -2.77 T-score STANDARD_DEVIATION 1.02 | -2.85 T-score STANDARD_DEVIATION 1 | -2.69 T-score STANDARD_DEVIATION 1.03 |
| Participants With Pre-Existing Anti-Romosozumab Antibodies Binding Antibody Positive at or Before BL | 3 Participants | 0 Participants | 3 Participants |
| Participants With Pre-Existing Anti-Romosozumab Antibodies Neutralizing Antibody Positive at or Before BL | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 279 Participants | 140 Participants | 139 Participants |
| Sex: Female, Male Female | 283 Participants | 142 Participants | 141 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Total Hip BMD T-Score | -2.29 T-score STANDARD_DEVIATION 0.75 | -2.30 T-score STANDARD_DEVIATION 0.77 | -2.29 T-score STANDARD_DEVIATION 0.73 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 141 | 0 / 142 |
| other Total, other adverse events | 48 / 141 | 64 / 142 |
| serious Total, serious adverse events | 7 / 141 | 4 / 142 |
Outcome results
Primary
Percent Change From Baseline in Lumbar Spine BMD at Month 6
Percent change from baseline in BMD at the lumbar spine as measured by dual-energy x-ray absorptiometry (DXA).
Time frame: Baseline, Month 6
Population: Primary Analysis Population: participants with lumbar spine BMD values at baseline and \>=1 postbaseline visit at Month 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Romosozumab 210 mg QM: PFS | Percent Change From Baseline in Lumbar Spine BMD at Month 6 | 9.2 percent change | Standard Error 0.4 |
| Romosozumab 210 mg QM: AI/Pen | Percent Change From Baseline in Lumbar Spine BMD at Month 6 | 9.0 percent change | Standard Error 0.5 |
p-value: 0.8495% CI: [-1.3, 1]ANCOVA
Secondary
Number of Participants Developing Anti-Romosozumab Antibodies
Participants with a negative or no result at baseline (BL) developing anti-romosozumab antibodies postbaseline, including those who were binding antibody-positive or neutralizing antibody-positive postbaseline. 'Transient' positive results are those with a negative result at the participant's last time point tested within the study period.
Time frame: up to Month 9 (-7/+3 days)
Population: Safety Analysis Set: all randomized participants who received at least 1 dose of study drug as well as baseline and postbaseline antibody results.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Romosozumab 210 mg QM: PFS | Number of Participants Developing Anti-Romosozumab Antibodies | Binding Antibody Positive Post-BL | 21 Participants |
| Romosozumab 210 mg QM: PFS | Number of Participants Developing Anti-Romosozumab Antibodies | Transient Binding Antibody Positive Post-BL | 6 Participants |
| Romosozumab 210 mg QM: PFS | Number of Participants Developing Anti-Romosozumab Antibodies | Neutralizing Antibody Positive Post-BL | 5 Participants |
| Romosozumab 210 mg QM: PFS | Number of Participants Developing Anti-Romosozumab Antibodies | Transient Neutralizing Antibody Positive Post-BL | 0 Participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants Developing Anti-Romosozumab Antibodies | Transient Neutralizing Antibody Positive Post-BL | 2 Participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants Developing Anti-Romosozumab Antibodies | Binding Antibody Positive Post-BL | 22 Participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants Developing Anti-Romosozumab Antibodies | Neutralizing Antibody Positive Post-BL | 4 Participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants Developing Anti-Romosozumab Antibodies | Transient Binding Antibody Positive Post-BL | 3 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths
AE: any untoward medical occurrence irrespective of a causal relationship with the study treatment. SAE: any untoward medical occurrence that meets at least 1 of the following criteria: results in death; is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important serious event. Adverse device effect: any AE related to the use of a combination product or medical device. TEAEs are those AEs occurring after first dose of study drug.
Time frame: up to Month 9 (-7/+3 days)
Population: Safety Analysis Set: all randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TEAEs: All | 94 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TEAEs: SAEs | 7 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TEAEs: Leading to Study Drug Discontinuation (DC) | 7 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TEAEs: Fatal | 0 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | Treatment-Related (TR) TEAEs: All | 38 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TR TEAEs: SAEs | 0 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TR TEAEs: Leading to Study Drug DC | 6 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TR TEAEs: Fatal | 0 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | Device-Related (DR) TEAEs: All | 18 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | DR TEAEs: SAEs | 0 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | DR TEAEs: Leading to Study Drug DC | 0 participants |
| Romosozumab 210 mg QM: PFS | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | DR TEAEs: Fatal | 0 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | DR TEAEs: Leading to Study Drug DC | 5 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TEAEs: All | 96 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TR TEAEs: Leading to Study Drug DC | 10 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TEAEs: SAEs | 4 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | DR TEAEs: SAEs | 0 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TEAEs: Leading to Study Drug Discontinuation (DC) | 15 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TR TEAEs: Fatal | 0 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TEAEs: Fatal | 0 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | DR TEAEs: Fatal | 0 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | Treatment-Related (TR) TEAEs: All | 59 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | Device-Related (DR) TEAEs: All | 30 participants |
| Romosozumab 210 mg QM: AI/Pen | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Device-Related AEs, Discontinuations Due to AEs, and Deaths | TR TEAEs: SAEs | 0 participants |
Secondary
Percent Change From Baseline in Femoral Neck BMD at Month 6
Percent change from baseline in BMD at femoral neck as measured by DXA.
Time frame: Baseline, Month 6
Population: Primary Analysis Population: participants with lumbar spine BMD values at baseline and \>=1 postbaseline visit at Month 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Romosozumab 210 mg QM: PFS | Percent Change From Baseline in Femoral Neck BMD at Month 6 | 3.4 percent change | Standard Error 0.7 |
| Romosozumab 210 mg QM: AI/Pen | Percent Change From Baseline in Femoral Neck BMD at Month 6 | 3.6 percent change | Standard Error 0.5 |
Secondary
Percent Change From Baseline in Total Hip BMD at Month 6
Percent change from baseline in BMD for total hip as measured by DXA.
Time frame: Baseline, Month 6
Population: Primary Analysis Population: participants with lumbar spine BMD values at baseline and \>=1 postbaseline visit at Month 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Romosozumab 210 mg QM: PFS | Percent Change From Baseline in Total Hip BMD at Month 6 | 3.7 percent change | Standard Error 0.6 |
| Romosozumab 210 mg QM: AI/Pen | Percent Change From Baseline in Total Hip BMD at Month 6 | 3.6 percent change | Standard Error 0.3 |