A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®

Inclusion Criteria

• Willing to provide voluntary written informed consent and able to comply with the protocol requirements
• Postmenopausal women aged ≥ 55 and ≤ 85 years globally, except for Spain. In Spain specifically refer to the below criteria:
• Postmenopausal women aged ≥ 75 and ≤ 85 years with LS T-score ≤ -2.5 or
• Postmenopausal women aged ≥ 65 and 3 years.
• Use of parathyroid hormone or its derivatives, hormone replacement therapy, romosozumab, selective estrogen-receptor modulators, or tibolone or calcitonin within 12 months prior to enrollment Note: occasional use of intravaginal estrogen treatment is not exclusionary
• Any prior use of fluoride or strontium
• Systemic glucocorticoids (≥ 5 mg prednisone equivalent per day or cumulative dose ≥ 50 mg) for more than 10 days within 3 months prior to enrollment (topical and inhaled corticosteroids are allowed)
• Other bone active drugs (i.e. drugs affecting bone metabolism) including heparin, anti epileptics (except for benzodiazepines and pregabalin), antidepressants such as SSRIs, SNRIs, antipsychotics, systemic ketoconazole, adrenocorticotrophic hormone (ACTH), lithium, protease inhibitors, gonadotropin releasing hormone (GnRH) agonists, or anabolic steroids within the past 3 months prior to screening or requiring treatment with these agents during the study.

Note: Please refer to Section 6.11 for a comprehensive list of prohibited medications

• Known sensitivity to drug products derived from mammalian cell lines such as hormones, enzymes, cytokines, bone morphogenic proteins, clotting factors, antibodies, and fusion protein therapeutics. Patients with any known hypersensitivity to complex proteins such as monoclonal antibodies will be excluded.
• History of one severe or more than two moderate vertebral fractures per Genant classification as determined by the central reading center
• History of hip fracture or bilateral hip replacement
• Total hip or femoral neck T-score 3 times upper limit of normal)
• Positive testing for hepatitis B (hepatitis B virus surface antigen [HbsAg]) or hepatitis C (hepatitis C virus antibody [HCV Ab]) virology
• Known history of human immunodeficiency virus (HIV) infection or positive serology for HIV at screening
• Significantly impaired renal function (determined by glomerular filtration rate of 10.6 mg/dL [> 2.62 mmol/L])
• History of parathyroid surgery
• Any bone or metabolic disease which may affect BMD or interfere with the interpretation of the findings, e.g., osteomalacia, osteogenesis imperfecta, osteopetrosis, achondroplasia, Paget's disease, rheumatoid arthritis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, or malabsorption syndrome
• Any malignancy, including solid tumors, and hematologic malignancies (except basal cell carcinoma and squamous cell carcinomas of the skin, cervical, or breast ductal carcinoma in situ, that have been completely excised and are considered cured) within the last 5 years
• Known or suspected history of alcoholism (including heavy drinking defined as consuming more than 3 drinks on one day or more than 7 drinks per week) or substance abuse within the past 12 months prior to the first dosing that the Investigator believes would interfere with understanding or completing the study
• Current heavy smoking, defined as smoking 20 or more cigarettes per day.
• Participated in any other clinical study in last 30 days prior to screening
• History and/or presence of significant cardiac disease as per Investigator's discretion, including but not restricted to:

i. History of cardiac arrhythmia or long QT syndrome or ECG abnormalities at screening indicating significant risk for safety (e.g., that required hospitalization, emergency cardioversion, or defibrillation) ii. History and/or presence of myocardial infarction within 6 months before screening iii. History and/or presence of New York Heart Association (NYHA) class III or IV heart failure

• Sus