Comparison of Efficacy, Pharmacodynamics, Safety, and Immunogenicity Between Bmab 1000 and Prolia® in Postmenopausal Women With Osteoporosis

Study Overview
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Brief Summary
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This is a randomized, double-blind, multicenter, parallel-arm, Phase 3 study to compare the efficacy, PK (Pharmacokinetic), PD (Pharmacodynamic), safety, and immunogenicity of Bmab 1000 and Prolia® in postmenopausal women with osteoporosis

Detailed Description
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The study will consist of 3 study periods: Screening period; Part 1, double-blind active-controlled period; and Part 2, transition period. In the double-blind active-controlled period, eligible Patients will be randomized in a 1:1 ratio to receive either Bmab 1000 or Prolia®. Prior to dosing At Week 52, patients in Prolia® treatment group will be randomized again in a 1:1 ratio to either continue on Prolia® or be transitioned to Bmab 1000. To maintain the study blinding, the patients in the original Bmab 1000 arm will also go through the re-randomization procedure; however, they will continue to receive Bmab 1000. The interventions (Bmab 1000 or Prolia®) will be administered subcutaneously every 6 months. End-of-study visit will be at Week 78 post randomization (Month 18).

Official Title
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A Randomized, Double-Blind, Multicenter, Parallel-Arm Phase 3 Study to Compare the Efficacy, Pharmacodynamics, Safety, and Immunogenicity Between Bmab 1000 and Prolia® in Postmenopausal Women With Osteoporosis

Conditions
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Postmenopausal Women With Osteoporosis

Intervention / Treatment
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* Biological: Bmab 1000
* Biological: Prolia®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women, aged ≥55 and <80 years at screening. Postmenopausal is defined as 12 months of spontaneous amenorrhea with serum FSH (follicle-stimulating hormone) levels ≥40 mIU/mL at screening or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. Evidence of osteoporosis as assessed by lumbar spine (L1-L4) absolute BMD corresponding to a T-score classification ≤-2.5 and ≥-4.0. At least 3 vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA at screening. Patients with body weight ≥50 to <90 kg at screening. Exclusion Criteria: Patients with T-score of <-4.0 at the lumbar spine, total hip, or femoral neck. Known history of previous exposure to denosumab (Prolia®, Xgeva®, or any biosimilar denosumab). For prior or ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements) following points to be considered for the washout periods prior to the screening visit: a. Oral bisphosphonate i. Ineligible if used for 3 or more years cumulatively ii. If used for <3 years, a gap of at least 1 year since the last dose is required at the screening visit b. Dose received any time Systemic glucocorticosteroids Patients with ongoing serious infections Evidence of any of the following per the patient's history, DXA, or X-ray review and/or current disease: Patient in bed rest for 2 or more weeks during the last 3 months prior to screening Current hyperthyroidism or hypothyroidism History and/or current hyperparathyroidism or hypoparathyroidism Current hypocalcemia or hypercalcemia based on albumin-adjusted serum calcium Any bone disease including bone metastasis or metabolic disease (except for osteoporosis), eg, osteomalacia or osteogenesis imperfecta, rheumatoid arthritis, Paget's disease, ALP (alkaline phosphatase) elevation (at investigator's discretion), Cushing's disease, clinically significant hyperprolactinemia (at investigator's discretion), fibrous dysplasia, malabsorption syndrome which may interfere with the interpretation of the results History and/or presence of one severe or 3 or more moderate vertebral fractures History and/or presence of hip fracture or bilateral hip replacement Presence of an active healing fracture according to assessment of investigator History of severe skeletal pain with bisphosphonates which, as per the investigator, is a risk to her participation in the trial Oral/dental or periodontal conditions:

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bmab 1000<br> | Biological: Bmab 1000<br>* 60 mg administered as a single SC (subcutaneous) injection once every 6 months.<br>|
| Active Comparator: Prolia®:<br> | Biological: Prolia®<br>* 60 mg administered as a single SC injection once every 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in lumbar spine BMD (Bone mineral density) | To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline at Week 52 in lumbar spine BMD | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUEC (Area under the effect curve) of the bone resorption marker sCTX (serum C-terminal telopeptide of Type 1 collagen) | To demonstrate pharmacodynamic equivalence between Bmab 1000 and Prolia® based on AUEC of the bone resorption marker sCTX from baseline to week 26 | Baseline to Week 26 | 
| Percentage change in lumbar spine BMD | To demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline at Week 26 in lumbar spine BMD | Baseline and Week 26 | 
| Percentage change in total hip BMD by DXA (Dual-energy X-ray absorptiometry) | o demonstrate equivalent efficacy between Bmab 1000 and Prolia® based on percentage change from baseline, at Week 26 and Week 52 in lumbar spine BMD | Baseline, at Week 26 and Week 52 | 
| Serum concentrations of P1NP (Procollagen Type 1 N-terminal propeptide) | To compare bone turnover between Bmab 1000 and Prolia® based on P1NP after the first dose | Baseline up to Week 52 | 
| Incidence of TEAEs (Treatment-emergent adverse events) up to 6 months after the second dose | To compare safety and tolerability of 2 administrations of Bmab 1000 and Prolia® 6 months apart | Baseline up to Week 52 | 
| Titer of ADA (Anti-drug antibody) | To compare immunogenicity between Bmab 1000 and Prolia® | Baseline up to Week 52 | 
| Incidence of ADA (Anti-drug antibody) | To compare immunogenicity between Bmab 1000 and Prolia® | Baseline up to Week 52 | 
| Incidence of NAb (Neutralizing antibody) up to Week 52 | To compare immunogenicity between Bmab 1000 and Prolia® | Baseline up to Week 52 |