A Study to Test the Efficacy, Safety and Tolerability of Romosozumab Treatment in Postmenopausal Chinese Women With Osteoporosis

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the effect of treatment with romosozumab for 6 months compared with placebo on the percent changes in bone mineral density (BMD) at the lumbar spine, at the total hip and femoral neck in postmenopausal Chinese women with osteoporosis.

Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Romosozumab Treatment in Postmenopausal Chinese Women With Osteoporosis

Conditions
-----------------
Osteoporosis

Intervention / Treatment
-----------------
* Drug: Romosozumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is considered reliable and capable of adhering to the protocol, visit schedule, and medication intake according to the judgment of the investigator Subject is an ambulatory postmenopausal Chinese women, 55 to 90 years of age (inclusive) at the time of Screening. Postmenopause is defined as no spontaneous vaginal bleeding or spotting for 12 or more consecutive months prior to Screening Subject has a bone mineral density (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, and using data for Caucasian women from the National Health and Nutritional Examination Survey (NHANES, 1998) Subject must have at least 1 of following independent risk factors for fracture: History of fragility fracture (except hip fracture, a severe vertebral fracture or more than 2 moderate vertebral fractures) Parental history of hip fracture Low body weight (body mass index ≤19kg/m2) Elderly (age ≥ 65 years) Current smoker Subject has at least 2 vertebrae in the L1 to L4 region and at least 1 hip that are evaluable by dual-energy x-ray absorptiometry (DXA), as assessed by the central imaging vendor Exclusion Criteria: Subject has a BMD T-score of ≤-3.50 at the total hip or femoral neck, as assessed by the central imaging vendor at the time of Screening based on DXA scans, and using data for Caucasian women from NHANES 1998 Subject has a known history of hip fracture Subject has any severe (SQ3) or more than 2 moderate (SQ2) vertebral fractures, as assessed by the central imaging vendor based on the lateral spine x-ray at Screening Subject has a history of myocardial infarction (MI) Subject has a history of stroke Subject has a vitamin D insufficiency, defined as 25 (OH) vitamin D levels <20 ng/mL, as assessed by the central laboratory at Screening. Vitamin D repletion will be permitted and the subject may be retested once within the Screening Period Subject has used oral bisphosphonates: Any doses received within 3 months prior to randomization More than 1 month of cumulative use between 3 and 12 months prior to randomization More than 3 years of cumulative use, unless the last dose was received ≥5 years prior to randomization Subject has used intravenous (iv) bisphosphonates: zoledronic acid Any doses received within 3 years prior to randomization More than 1 dose received within 5 years prior to randomization iv ibandronate, iv pamidronate, or iv alendronate (ALN) Any doses received within 12 months prior to randomization More than 3 years of cumulative use, unless the last dose was received ≥5 years prior to randomization Subject has used denosumab or any cathepsin K inhibitor: ● Any doses received within 18 months prior to randomization Subject has used tibolone, cinacalcet, or calcitonin: Any doses received within 3 months prior to randomization Subject has used teriparatide (TPTD) or any parathyroid hormone (PTH) derivative: Any doses received within 3 months prior to randomization More than 1 month of cumulative use between 3 and 12 months prior to randomization Subject has used systemic oral or transdermal estrogen or selective estrogen receptor modulators (SERMs): ● More than 1 month of cumulative use within 6 months prior to randomization Subject has used strontium ranelate or fluoride: ● More than 1 month of cumulative use within 5 years prior to randomization Subject has used hormonal ablation therapy: ● More than 1 month of cumulative use within 6 months prior to randomization Subject has used systemic glucocorticosteroids: ● ≥5mg prednisone equivalent per day for more than 14 days within 3 months prior to randomization Subject has a history of osteonecrosis of the jaw (ONJ) or atypical femoral fracture (AFF) Subject has evidence of any of the following: Current, uncontrolled hyper- or hypothyroidism. Uncontrolled hyperthyroidism is defined as thyroid-stimulating hormone (TSH) and thyroxine (T4) outside of the normal range. Uncontrolled hypothyroidism is defined as TSH >10 Current, uncontrolled hyperparathyroidism or history of hypoparathyroidism. Uncontrolled hyperparathyroidism is defined as PTH outside the normal range in subjects with concurrent hypercalcemia or PTH values >20 % above upper limit of normal (ULN) in normocalcemic subjects Current hypercalcemia or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory at the time of Screening. Albumin-adjusted serum calcium levels may be retested once in case of an elevated albumin-adjusted serum calcium level within 1.1xULN of the laboratory's reference ranges Subject has ≥3xULN of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin <35 %)

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

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romosozumab<br>Subjects randomized to this arm will receive romosozumab during all treatment Periods. | Drug: Romosozumab<br>* Subjects will receive romosozumab in a specified sequence during the treatment Period.<br>|
| Placebo Comparator: Placebo<br>Subjects randomized to this arm will receive placebo during the Double-Blind-Placebo controlled Period and romosozumab during the Open-Label treatment Period | Drug: Romosozumab<br>* Subjects will receive romosozumab in a specified sequence during the treatment Period.<br>Drug: Placebo<br>* Subjects will receive Placebo in a specified sequence during the treatment Period.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from Baseline in bone mineral density (BMD) at the lumbar spine | Percent change from Baseline in bone mineral density (BMD) at the lumbar spine at the end of the Double-Blind, Placebo-Controlled Period (Month 6) as assessed by dual-energy x-ray absorptiometry (DXA) by treatment group. | From Baseline to the end of the Double-Blind, Placebo-Controlled Period (Month 6) | 
| Incidence of treatment-emergent adverse events (TEAEs) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline to the end of the Double-Blind, Placebo-Controlled Period (Month 6) | 
| Incidence of treatment-emergent adverse events (TEAEs) during the Open-Label Treatment Period | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From the Open-Label Treatment Period up to Month 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from Baseline in bone mineral density (BMD) at the total hip | Percent change from Baseline in bone mineral density (BMD) at the total hip at the end of the Double-Blind, Placebo-Controlled Period (Month 6) as assessed by dual-energy x-ray absorptiometry (DXA) by treatment group. | From Baseline to the end of the Double-Blind, Placebo-Controlled Period (Month 6) | 
| Percent change from Baseline in bone mineral density (BMD) at the femoral neck | Percent changes from Baseline in bone mineral density (BMD) at the femoral neck at the end of the Double-Blind, Placebo-Controlled Period (Month 6) as assessed by dual-energy x-ray absorptiometry (DXA) by treatment group. | From Baseline to the end of the Double-Blind, Placebo-Controlled Period (Month 6) | 
| Percent change from Baseline in bone mineral density (BMD) at the lumbar spine at the end of the Open-Label Treatment Period | Percent change from Baseline in bone mineral density (BMD) at the lumbar spine, at the end of OLE Period (Month 12) as assessed by dual-energy x-ray absorptiometry (DXA) in subjects who are continuing with 6 months of romosozumab treatment after initially being randomized to 6 months of romosozumab treatment in the Double-Blind, Placebo-Controlled Period (for a total of 12 months of romosozumab treatment). | From Baseline to the end of the Open-Label Extension (OLE) Period (Month 12) | 
| Percent change from Baseline in bone mineral density (BMD) at the total hip at the end of the Open-Label Treatment Period | Percent change from Baseline in bone mineral density (BMD) at the total hip, at the end of OLE Period (Month 12) as assessed by dual-energy x-ray absorptiometry (DXA) in subjects who are continuing with 6 months of romosozumab treatment after initially being randomized to 6 months of romosozumab treatment in the Double-Blind, Placebo-Controlled Period (for a total of 12 months of romosozumab treatment). | From Baseline to the end of the Open-Label Extension (OLE) Period (Month 12) | 
| Percent change from Baseline in bone mineral density (BMD) at the femoral neck at the end of the Open-Label Treatment Period | Percent change from Baseline in bone mineral density (BMD) at the femoral neck, at the end of OLE Period (Month 12) as assessed by dual-energy x-ray absorptiometry (DXA) in subjects who are continuing with 6 months of romosozumab treatment after initially being randomized to 6 months of romosozumab treatment in the Double-Blind, Placebo-Controlled Period (for a total of 12 months of romosozumab treatment). | From Baseline to the end of the Open-Label Extension (OLE) Period (Month 12) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Osteoporosis, Phase 3, Chinese Patients, Romosozumab