A Study to Compare Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of MB09 [Proposed Denosumab Biosimilar] to Prolia® [EU-sourced] in Postmenopausal Osteoporosis (SIMBA Study)

Study Overview
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Brief Summary
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This is a randomized, double-blind, parallel, multicenter, multinational study to compare the efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of MB09 versus Prolia® in postmenopausal women with osteoporosis

Detailed Description
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The study will randomise approximately 528 postmenopausal women with osteoporosis aged ≥55 and ≤80 years old with a Bone Mineral Density (BMD) consistent with T-score of ≤ -2.5 and ≥ -4 at the lumbar spine or hip as measured by DXA during the Screening Period. Screening evaluations will be completed within 28 days prior to randomisation. On Day 1, 528 eligible postmenopausal women with osteoporosis will be randomised in a 2:1:1 ratio to re-ceive MB09-MB09 (Arm 1), Prolia-MB09 (Arm 2), or Prolia-Prolia (Arm 3) using an Interactive Response Sys-tem (IRT). During the Main Treatment Period, subjects will receive one subcutaneous injection (60 mg/mL) of study drug on Day 1 and at Month 6. At Month 12, after all efficacy and safety assessments have been performed, the subject will enter the Transition/Safety Follow Up Period and will receive the third dose of study drug. Subjects assigned to the MB09 MB09 arm (Arm 1) will receive MB09 on Day 1, at Month 6 and at Month 12. Subjects assigned to the Prolia MB09 arm (Arm 2) will receive EU-Prolia on Day 1 and at Month 6, and MB09 at Month 12. Subjects assigned to the Prolia-Prolia arm (Arm 3) will receive EU-Prolia on Day 1, at Month 6, and at Month 12. All subjects will be followed up to Transition Period Month 6. All subjects will receive daily supplementation of calcium and vitamin D.

Official Title
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A Randomised, Double-blind, Parallel, Multicentre, Multinational Study to Compare the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of MB09 (Proposed Denosumab Biosimilar) Versus Prolia® (EU-sourced) in Postmenopausal Women With Osteoporosis (SIMBA Study)

Conditions
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Postmenopausal Women With Osteoporosis

Intervention / Treatment
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* Drug: MB09 (denosumab biosimilar)
* Drug: EU-Prolia
* Dietary Supplement: Elemental Calcium
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women, diagnosed with osteoporosis. Aged ≥ 55 and ≤ 80 years at screening. Body weight ≥ 50 kg and ≤ 99.9 kg, and a body mass index of ≤30 kg/m2 at screening. Absolute bone mineral density consistent with T-score ≤ -2.5 and ≥ -4.0 at the lumbar spine or total hip as measured by DXA. At least two intact, nonfractured vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA. Adequate organ function. Exclusion Criteria: Previous exposure to denosumab (Prolia®, Xgeva®, or denosumab biosimilar) or other monoclonal anti-body. History and/or presence of one severe or more than two moderate vertebral fractures or hip fracture. Recent long bone fracture (6 months). History and/or presence of bone metastases, bone disease or other metabolic disease. Ongoing use of any osteoporosis treatment or use of prohibited treatment. Other bone active drugs. History and/or current hypoparathyroidism or hyperparathyroidism, hypocalcemia or hypercalcemia. Other Inclusion/exclusion criteria may apply.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MB09-MB09<br>Subjects randomised into MB09-MB09 group will receive MB09 (60 mg in 1 mL) SC injection every 6 months. | Drug: MB09 (denosumab biosimilar)<br>* PFS 60 mg/mL solution,<br>Dietary Supplement: Elemental Calcium<br>* at least 1000 mg daily<br>Dietary Supplement: Vitamin D<br>* at least 400 IU daily<br>|
| Active Comparator: Prolia-MB09<br>Subjects randomised into Prolia- MB09 group will receive Prolia® (60 mg in 1 mL) SC injection every 6 months. | Drug: MB09 (denosumab biosimilar)<br>* PFS 60 mg/mL solution,<br>Drug: EU-Prolia<br>* PFS 60 mg/mL solution, administered as subcutaneous injection<br>Dietary Supplement: Elemental Calcium<br>* at least 1000 mg daily<br>Dietary Supplement: Vitamin D<br>* at least 400 IU daily<br>|
| Active Comparator: Prolia-Prolia<br>Subjects randomised into Prolia-Prolia group will receive Prolia® (60 mg in 1 mL) SC injection every 6 months. | Drug: EU-Prolia<br>* PFS 60 mg/mL solution, administered as subcutaneous injection<br>Dietary Supplement: Elemental Calcium<br>* at least 1000 mg daily<br>Dietary Supplement: Vitamin D<br>* at least 400 IU daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in lumbar spine bone mineral density (BMD) at Month 12 |  | Baseline and at Month 12 |