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

• ClinicalTrials.gov Identifier: NCT04729621
• Recruitment Status: Completed
• First Posted: January 28, 2021
• Results First Posted: April 18, 2024
• Last Update Posted: April 18, 2024
• Sponsor: Teva Pharmaceuticals USA
• Collaborator: Teva Branded Pharmaceutical Products R&D, Inc.
• Information provided by (Responsible Party): Teva Pharmaceuticals USA

Tracking Information

• First Submitted Date: January 25, 2021
• First Posted Date: January 28, 2021
• Results First Submitted Date: January 4, 2024
• Results First Posted Date: April 18, 2024
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: March 22, 2021
• Actual Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 4, 2024)

Percent Change From Baseline in LS-BMD at Week 52 [ Time Frame: Baseline and 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

Original Primary Outcome Measures (submitted: January 25, 2021)

Percent change from baseline in LS-BMD at week 52 [ Time Frame: Baseline and 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

Current Secondary Outcome Measures (submitted: April 9, 2024)

• Percent Change From Baseline in sCTX-1 at Week 26 [ Time Frame: Baseline and week 26 ]
  Percent change from baseline in serum C-telopeptide cross-link of type 1 collagen at week 26
• Percent Change From Baseline in LS-BMD at Week 26 [ Time Frame: Baseline and 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
• Percent Change From Baseline in Femoral Neck BMD at Week 26 [ Time Frame: Baseline, week 26 ]
  Percent change from baseline in femoral neck bone mineral density (BMD) based on centrally assessed dual energy X ray absorptiometry (DXA)at week 26
• Percent Change From Baseline in Total Hip BMD at Week 26 [ Time Frame: Baseline, week 26 ]
  Percent change from baseline in total hip bone mineral density (BMD) based on centrally assessed dual energy X ray absorptiometry (DXA) at week 26
• Percent Change From Baseline in sCTX-1 [ Time Frame: Baseline through Week 52 ]
  Percent change from baseline in serum C-telopeptide cross-link of type 1 collagen
• Percentage of Participatns With sCTX-1 Suppression at Week 4 [ Time Frame: Week 4 ]
  Proportion of patients with suppression of serum C-telopeptide cross-link of type 1 collagen at week 4
• Percent Change From Baseline in P1NP [ Time Frame: Baseline through Week 52 ]
  Percent change from baseline in procollagen type 1 N propeptide (P1NP) to Week 52
• Number of Fractures up to Week 52 [ Time Frame: Up to week 52 ]
  Number of patients with who experienced any new fractures up to week 52.
• Percent Change From Week 52 in LS-BMD by DXA at Week 78 [ Time Frame: Week 52 through 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
• Percent Change From Week 52 in Femoral Neck BMD by DXA at Week 78 [ Time Frame: Week 52 through 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
• Percent Change From Week 52 in Total Hip BMD by DXA at Week 78 [ Time Frame: Week 52 through 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
• Difference Between Percent Change From Baseline in sCTX-1 Between Week 52 and Week 78 [ Time Frame: Baseline, Week 52, Week 78 ]
  Difference in the percent change from baseline in serum C-telopeptide cross-link of type 1 collagen from baseline to Week 78 as compared to baseline to Week 52
• Difference Between Percent Change From Baseline in P1NP Between Week 52 and Week 78 [ Time Frame: Baseline, Week 52, Week 78 ]
  The difference in the Percent change from baseline in procollagen type 1 N propeptide at Week 78 compared to Week 52.
• Number of Patients With Fractures Between Week 52 and Week 78 [ Time Frame: Week 52 through week 78 ]
  Number of patients experiencing new fractures between week 52 and week 78
• Incidence of Adverse Event [ Time Frame: Up to week 52 ]
  Number of patients reporting at least one treatment-emergent adverse event up to week 52
• Incidence of Adverse Events in the Transition Period [ Time Frame: Week 52 through week 78 ]
  Number of patients reporting at least one treatment-emergent adverse event between weeks 52 and 78
• Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period [ Time Frame: Anytime Post Baseline through Week 52 ]
  Number of patients with confirmed positive antidrug antibodies (ADAs) post-baseline through Week 52
• Incidence of Antidrug Antibodies (ADAs) in the Transition Period [ Time Frame: Anytime in Week 52 through Week 78 ]
  Number of patients with confirmed positive antidrug antibodies (ADAs) at Week 65
• Percent Change From Baseline in Femoral Neck BMD at Week 52 [ Time Frame: Baseline through Week 52 ]
  Percent change from baseline in femoral neck bone mineral density (BMD) based on centrally assessed dual energy X ray absorptiometry (DXA)at week 52
• Percent Change From Baseline in Total Hip BMD at Week 52 [ Time Frame: Baseline through Week 52 ]
  Percent change from baseline in total hip bone mineral density (BMD) based on centrally assessed dual energy X ray absorptiometry (DXA) at week 52
• Number of TEAEs Leading to Patient Withdraw From the Study [ Time Frame: Main Treatment Period = Baseline-Week 52; Transition period = Week 52-78 ]
  Number of patients that withdraw or are removed from the study due to treatment emergent adverse events from both the main and transition treatment periods.
• Local Tolerability at Injection Site [ Time Frame: Main Treatment Period = Day 1 & Week 26; Transition Treatment Period = Week 52 ]
  Number of patients who report Injection Site Reactions at Day 1, Week 26, or Week 52.

Original Secondary Outcome Measures (submitted: January 25, 2021)

• Percent change from baseline in sCTX-1 at week 26 [ Time Frame: Baseline and week 26 ]
  Percent change from baseline in serum C-telopeptide cross-link of type 1 collagen at week 26
• Percent change from baseline in LS-BMD at week 26 [ Time Frame: Baseline and 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
• Percent change from baseline in femoral neck BMD [ Time Frame: Baseline, week 26, week 52 ]
  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
• Percent change from baseline in total hip BMD [ Time Frame: Baseline, week 26, week 52 ]
  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
• Percent change from baseline in sCTX-1 [ Time Frame: Baseline through week 52 ]
  Percent change from baseline in serum C-telopeptide cross-link of type 1 collagen
• sCTX-1 suppression at week 4 [ Time Frame: Week 4 ]
  Proportion of patients with suppression of serum C-telopeptide cross-link of type 1 collagen at week 4
• Percent change from baseline in P1NP [ Time Frame: Baseline, week 26, week 52 ]
  Percent change from baseline in procollagen type 1 N propeptide (P1NP) at week 26 and week 52
• Incidence of fractures up to week 52 [ Time Frame: Up to week 52 ]
  Number of patients with fractures up to week 52
• Percent change from week 52 in LS-BMD by DXA at week 78 [ Time Frame: Week 52 through 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
• Percent change from week 52 in femoral neck BMD by DXA at week 78 [ Time Frame: Week 52 through 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
• Percent change from week 52 in total hip BMD by DXA at week 78 [ Time Frame: Week 52 through 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
• Difference between percent change from baseline in sCTX-1 at weeks 52 and 78 [ Time Frame: Week 52 through week 78 ]
  Difference between percent change from baseline in serum C-telopeptide cross-link of type 1 collagen at weeks 52 and 78
• Difference between percent change from baseline in P1NP at weeks 52 and 78 [ Time Frame: Week 52 through week 78 ]
  Difference between percent change from baseline in procollagen type 1 N propeptide at weeks 52 and 78
• Incidence of fractures between week 52 and week 78 [ Time Frame: Week 52 through week 78 ]
  Number of patients with fractures between week 52 and week 78
• Incidence of adverse event and withdrawals due to adverse events [ Time Frame: Up to week 52 ]
  Number of patients reporting at least one treatment-emergent adverse event up to week 52
• Incidence of adverse events in the transition period [ Time Frame: Week 52 through week 78 ]
  Number of patients reporting at least one treatment-emergent adverse event between weeks 52 and 78
• Incidence of antidrug antibodies (ADAs) in the main treatment period [ Time Frame: Up to week 52 ]
  Number of patients with confirmed positive antidrug antibodies (ADAs) post-baseline up to week 52
• Incidence of antidrug antibodies (ADAs) in the transition period [ Time Frame: Week 52 through week 78 ]
  Number of patients with confirmed positive antidrug antibodies (ADAs) between week 52 and 78

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Test if TVB-009P is Effective in Relieving Postmenopausal Osteoporosis
• Official Title: A Randomized, Double-Blind, Multinational, Multicenter Study to Compare Efficacy, Safety, and Immunogenicity of TVB-009P and Denosumab (Prolia®) in Patients With Postmenopausal Osteoporosis
• Brief Summary: The purpose of this study is to demonstrate similar efficacy and safety between TVB-009 and Prolia® (denosumab)
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Osteoporosis, Postmenopausal

Intervention

• Combination Product: TVB-009
  TVB-009 Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)
• Combination Product: Prolia®
  Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)

Study Arms

• Experimental: TVB-009 main treatment period
  TVB-009 (denosumab) pre-filled syringe, administered at weeks 1 and 26
  Intervention: Combination Product: TVB-009
• Active Comparator: PROLIA main treatment period
  Prolia® (denosumab) pre-filled syringe, administered at weeks 1 and 26
  Intervention: Combination Product: Prolia®
• Experimental: TVB-009 main / TVB-009 transition period
  TVB-009 (denosumab) pre-filled syringe, administered at week 52 in patients that were randomized to TVB-009 in the main treatment period
  Intervention: Combination Product: TVB-009
• Active Comparator: PROLIA main / PROLIA transition period
  Prolia® (denosumab) pre-filled syringe, administered at week 52 in patients that were randomized to PROLIA in the main treatment period
  Intervention: Combination Product: Prolia®
• Experimental: PROLIA main / TVB-009 transition period
  TVB-009 (denosumab) pre-filled syringe, administered at week 52 in patients that were randomized to PROLIA in the main treatment period
  Interventions:

  • Combination Product: TVB-009
  • Combination Product: Prolia®

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 21, 2023): 332
• Original Estimated Enrollment (submitted: January 25, 2021): 326
• Actual Study Completion Date: June 19, 2023
• Actual Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 60 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Czechia, Georgia, Germany, Hungary, Poland, Russian Federation, Slovakia, Ukraine, United States

Administrative Information

• NCT Number: NCT04729621
• Other Study ID Numbers: TVB009-IMB-30085
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Teva Pharmaceuticals USA
• Original Responsible Party: Same as current
• Current Study Sponsor: Teva Pharmaceuticals USA
• Original Study Sponsor: Same as current
• Collaborators: Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Teva Medical Expert, MD; Teva Pharmaceuticals, Inc.

• PRS Account: Teva Pharmaceuticals USA
• Verification Date: April 2024