A Comparison of Subject-administered Romosozumab With Healthcare Provider-administered Romosozumab for Osteoporosis

Study Overview
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Brief Summary
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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)

Official Title
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A Randomized, Multicenter, Open-label, Parallel Group Study in Postmenopausal Women With Osteoporosis to Evaluate the Noninferiority of Subject-administered Romosozumab Via Autoinjector/Pen vs Healthcare Provider-administered Romosozumab Via Prefilled Syringe

Conditions
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Post-Menopausal Osteoporosis

Intervention / Treatment
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* Drug: romosozumab HCP administration with PFS
* Device: romosozumab self-administration with AI/Pen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Romosozumab 210 mg QM: PFS<br>During the open-label treatment period, participants receive 210 mg romosozumab SC QM by HCP administration with PFS. | Drug: romosozumab HCP administration with PFS<br>* 210 mg romosozumab SC QM by HCP administration with 2 PFS<br>* Other names: AMG785;|
| Active Comparator: Romosozumab 210 mg QM: AI/Pen<br>During the open-label treatment period, participants receive 210 mg romosozumab SC QM by self-administration with AI/pen. | Device: romosozumab self-administration with AI/Pen<br>* 210 mg romosozumab SC QM by self-administration with 2 AI/Pens<br>* Other names: AMG785;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline, Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Total Hip BMD at Month 6 | Percent change from baseline in BMD for total hip as measured by DXA. | Baseline, Month 6 | 
| Percent Change From Baseline in Femoral Neck BMD at Month 6 | Percent change from baseline in BMD at femoral neck as measured by DXA. | Baseline, Month 6 | 
| 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. | up to Month 9 (-7/+3 days) | 
| 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. | up to Month 9 (-7/+3 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-Menopausal osteoporosis