A Study to Test if TVB-009P is Effective in Relieving Postmenopausal Osteoporosis

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate similar efficacy and safety between TVB-009 and Prolia® (denosumab)

Detailed Description
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This is a multinational, multicenter, randomized, double-blind study to demonstrate similar efficacy and safety of TVB-009 compared to Prolia® administered subcutaneously at doses of 60 mg every 26 weeks. Approximately 326 postmenopausal women with osteoporosis will be randomized to receive either TVB-009 or Prolia®. At week 52, patients in the Prolia® arm will be re-randomized 1:1 to either continue with a third dose of Prolia® or transition to TVB-009 and receive a single dose of TVB-009 in the transition period to assess immunogenicity and safety after a transition from Prolia® to TVB-009. The total treatment duration for each patient is 78 weeks.

Official Title
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A Randomized, Double-Blind, Multinational, Multicenter Study to Compare Efficacy, Safety, and Immunogenicity of TVB-009P and Denosumab (Prolia®) in Patients With Postmenopausal Osteoporosis

Conditions
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Osteoporosis, Postmenopausal

Intervention / Treatment
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* Combination Product: TVB-009
* Combination Product: Prolia®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal womeen (≥60 and ≤90 years) with a diagnosis of osteoporosis Body weight ≥50 kg and ≤90 kg Bone Mineral Density (BMD) measurement T score of less than 2.5 but not less than 4.0 by dual-energy X-ray absorptiometry (DXA) at the lumbar spine at screening At least 3 vertebrae in the L1 L4 region that are evaluable by dual-energy X-ray absorptiometry (DXA) Exclusion Criteria: One severe or more than two moderate vertebral fractures History and/or presence of hip fracture or atypical femur fracture Any prior treatment with denosumab Ongoing use of any bone active drugs which can affect Bone Mineral Density (BMD) Vitamin D deficiency or hyper- or hypocalcemiacium at screening Hyperthyroidism, hypothyroidism, hypoparathyroidism or hyperparathyroidism Any medical condition that could jeopardize or would compromise the patient's safety or ability to participate in this study Other Inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 60 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TVB-009 main treatment period<br>TVB-009 (denosumab) pre-filled syringe, administered at weeks 1 and 26 | Combination Product: TVB-009<br>* TVB-009 Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)<br>|
| Active Comparator: PROLIA main treatment period<br>Prolia® (denosumab) pre-filled syringe, administered at weeks 1 and 26 | Combination Product: Prolia®<br>* Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)<br>|
| Experimental: TVB-009 main / TVB-009 transition period<br>TVB-009 (denosumab) pre-filled syringe, administered at week 52 in patients that were randomized to TVB-009 in the main treatment period | Combination Product: TVB-009<br>* TVB-009 Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)<br>|
| Active Comparator: PROLIA main / PROLIA transition period<br>Prolia® (denosumab) pre-filled syringe, administered at week 52 in patients that were randomized to PROLIA in the main treatment period | Combination Product: Prolia®<br>* Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)<br>|
| Experimental: PROLIA main / TVB-009 transition period<br>TVB-009 (denosumab) pre-filled syringe, administered at week 52 in patients that were randomized to PROLIA in the main treatment period | Combination Product: TVB-009<br>* TVB-009 Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)<br>Combination Product: Prolia®<br>* Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in LS-BMD at week 52 | Percent change from baseline in lumbar spine bone mineral density (LS BMD) based on centrally assessed dual energy X ray absorptiometry (DXA) at week 52 | Baseline and week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in sCTX-1 at week 26 | Percent change from baseline in serum C-telopeptide cross-link of type 1 collagen at week 26 | Baseline and week 26 | 
| Percent change from baseline in LS-BMD at week 26 | Percent change from baseline in lumbar spine bone mineral density (LS BMD) based on centrally assessed dual energy X ray absorptiometry (DXA) at week 26 | Baseline and week 26 | 
| Percent change from baseline in femoral neck BMD | Percent change from baseline in femoral neck bone mineral density (BMD) based on centrally assessed dual energy X ray absorptiometry (DXA)at week 26 and at week 52 | Baseline, week 26, week 52 | 
| Percent change from baseline in total hip BMD | Percent change from baseline in total hip bone mineral density (BMD) based on centrally assessed dual energy X ray absorptiometry (DXA) at week 26 and at week 52 | Baseline, week 26, week 52 | 
| Percent change from baseline in sCTX-1 | Percent change from baseline in serum C-telopeptide cross-link of type 1 collagen | Baseline through week 52 | 
| sCTX-1 suppression at week 4 | Proportion of patients with suppression of serum C-telopeptide cross-link of type 1 collagen at week 4 | Week 4 | 
| Percent change from baseline in P1NP | Percent change from baseline in procollagen type 1 N propeptide (P1NP) at week 26 and week 52 | Baseline, week 26, week 52 | 
| Incidence of fractures up to week 52 | Number of patients with fractures up to week 52 | Up to week 52 | 
| Percent change from week 52 in LS-BMD by DXA at week 78 | Percent change from week 52 in lumbar spine bone mineral density (LS BMD) based on centrally assessed dual energy X ray absorptiometry (DXA) at week 78 | Week 52 through week 78 | 
| Percent change from week 52 in femoral neck BMD by DXA at week 78 | Percent change from week 52 in femoral neck bone mineral density (LS BMD) based on centrally assessed dual energy X ray absorptiometry (DXA) at week 78 | Week 52 through week 78 | 
| Percent change from week 52 in total hip BMD by DXA at week 78 | Percent change from week 52 in total hip bone mineral density (LS BMD) based on centrally assessed dual energy X ray absorptiometry (DXA) at week 78 | Week 52 through week 78 | 
| Difference between percent change from baseline in sCTX-1 at weeks 52 and 78 | Difference between percent change from baseline in serum C-telopeptide cross-link of type 1 collagen at weeks 52 and 78 | Week 52 through week 78 | 
| Difference between percent change from baseline in P1NP at weeks 52 and 78 | Difference between percent change from baseline in procollagen type 1 N propeptide at weeks 52 and 78 | Week 52 through week 78 | 
| Incidence of fractures between week 52 and week 78 | Number of patients with fractures between week 52 and week 78 | Week 52 through week 78 | 
| Incidence of adverse event and withdrawals due to adverse events | Number of patients reporting at least one treatment-emergent adverse event up to week 52 | Up to week 52 | 
| Incidence of adverse events in the transition period | Number of patients reporting at least one treatment-emergent adverse event between weeks 52 and 78 | Week 52 through week 78 | 
| Incidence of antidrug antibodies (ADAs) in the main treatment period | Number of patients with confirmed positive antidrug antibodies (ADAs) post-baseline up to week 52 | Up to week 52 | 
| Incidence of antidrug antibodies (ADAs) in the transition period | Number of patients with confirmed positive antidrug antibodies (ADAs) between week 52 and 78 | Week 52 through week 78 |