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

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

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

Study Overview

• Status: Completed
• Conditions: Osteoporosis, Postmenopausal
• Intervention / Treatment: Combination product: TVB-009; Combination product: Prolia®

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
• Enrollment (Actual): 332
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Blagoevgrad, Bulgaria
    • Teva Site 203
  • Dimitrovgrad, Bulgaria
    • Teva Site 207
  • Haskovo, Bulgaria
    • Teva Site 252
  • Lom, Bulgaria
    • Teva Site 202
  • Plovdiv, Bulgaria
    • Teva Site 205
  • Silistra, Bulgaria
    • Teva Site 250
  • Sofia, Bulgaria
    • Teva Site 201
  • Sofia, Bulgaria
    • Teva Site 204
  • Sofia, Bulgaria
    • Teva Site 251
  • Stara Zagora, Bulgaria
    • Teva Site 206
• Czechia
  • Brno, Czechia
    • Teva Site 211
  • Ostrava, Czechia
    • Teva Site 213
  • Pardubice, Czechia
    • Teva Site 212
  • Praha, Czechia
    • Teva Site 209
  • Praha, Czechia
    • Teva Site 210
  • Uherské Hradiště, Czechia
    • Teva Site 208
• Georgia
  • Tbilisi, Georgia
    • Teva Site 214
  • Tbilisi, Georgia
    • Teva Site 215
  • Tbilisi, Georgia
    • Teva Site 216
  • Tbilisi, Georgia
    • Teva Site 217
  • Tbilisi, Georgia
    • Teva Site 218
  • Tbilisi, Georgia
    • Teva Site 219
• Germany
  • Dresden, Germany
    • Teva Site 223
  • Hamburg, Germany
    • Teva Site 220
  • Numbrecht, Germany
    • Teva Site 221
  • Würzburg, Germany
    • Teva Site 222
• Hungary
  • Balatonfüred, Hungary
    • Teva Site 226
  • Budapest, Hungary
    • Teva Site 225
  • Budapest, Hungary
    • Teva Site 227
  • Budapest, Hungary
    • Teva Site 253
  • Nyiregyhaza, Hungary
    • Teva Site 224
• Poland
  • Białystok, Poland
    • Teva Site 228
  • Kraków, Poland
    • Teva Site 233
  • Warsaw, Poland
    • Teva Site 230
  • Warsaw, Poland
    • Teva Site 232
  • Wrocław, Poland
    • Teva Site 229
  • Łódź, Poland
    • Teva Site 231
• Russian Federation
  • Moscow, Russian Federation
    • Teva Site 235
  • Saint Petersburg, Russian Federation
    • Teva Site 236
  • Saint Petersburg, Russian Federation
    • Teva Site 254
  • Saint Petersburg, Russian Federation
    • Teva Site 255
  • Saint Petersburg, Russian Federation
    • Teva Site 256
  • Saint Petersburg, Russian Federation
    • Teva Site 257
  • Yaroslavl, Russian Federation
    • Teva Site 234
  • Yaroslavl, Russian Federation
    • Teva Site 258
• Slovakia
  • Bratislava, Slovakia
    • Teva Site 238
  • Bratislava, Slovakia
    • Teva Site 242
  • Hlohovec, Slovakia
    • Teva Site 237
  • Lubochna, Slovakia
    • Teva Site 240
  • Lučenec, Slovakia
    • Teva Site 241
  • Prešov, Slovakia
    • Teva Site 239
• Ukraine
  • Kyiv, Ukraine
    • Teva Site 244
  • Kyiv, Ukraine
    • Teva Site 245
  • Kyiv, Ukraine
    • Teva Site 247
  • Kyiv, Ukraine
    • Teva Site 248
  • Kyiv, Ukraine
    • Teva Site 249
  • Vinnytsia, Ukraine
    • Teva Site 243
  • Zaporizhia, Ukraine
    • Teva Site 246
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Teva Site 103
    • Tucson, Arizona, United States, 85704
      • Teva Site 119
  • California
    • San Diego, California, United States, 92111
      • Teva Site 118
  • Connecticut
    • New London, Connecticut, United States, 06320
      • Teva Site 107
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Teva Site 115
    • Edgewater, Florida, United States, 32132
      • Teva Site 114
    • Lake City, Florida, United States, 32055
      • Teva Site 116
    • Miami Lakes, Florida, United States, 33014
      • Teva Site 109
    • Miami Springs, Florida, United States, 33166
      • Teva Site 117
    • Oldsmar, Florida, United States, 34677
      • Teva Site 110
    • Orlando, Florida, United States, 32801
      • Teva Site 120
    • Ormond Beach, Florida, United States, 32174
      • Teva Site 102
    • Port Saint Lucie, Florida, United States, 34952
      • Teva Site 101
    • Sarasota, Florida, United States, 34239
      • Teva Site 111
    • Tamarac, Florida, United States, 33321
      • Teva Site 104
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Teva Site 112
    • North Las Vegas, Nevada, United States, 89030
      • Teva Site 113
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Teva Site 105
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Teva Site 108
  • Washington
    • Seattle, Washington, United States, 98105
      • Teva Site 106

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TVB-009 main treatment period; TVB-009 (denosumab) pre-filled syringe, administered at weeks 1 and 26	Combination product: TVB-009; TVB-009 Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)
Active Comparator: PROLIA main treatment period; Prolia® (denosumab) pre-filled syringe, administered at weeks 1 and 26	Combination product: Prolia®; Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)
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	Combination product: TVB-009; TVB-009 Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)
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	Combination product: Prolia®; Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)
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	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)

What is the study measuring?

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 at 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	Baseline, week 26
Percent Change From Baseline in Total Hip BMD at 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	Baseline, week 26
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
Percentage of Participatns With 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) to Week 52	Baseline through Week 52
Number of Fractures up to Week 52	Number of patients with who experienced any new 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 Between Week 52 and 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	Baseline, Week 52, Week 78
Difference Between Percent Change From Baseline in P1NP Between Week 52 and Week 78	The difference in the Percent change from baseline in procollagen type 1 N propeptide at Week 78 compared to Week 52.	Baseline, Week 52, Week 78
Number of Patients With Fractures Between Week 52 and Week 78	Number of patients experiencing new fractures between week 52 and week 78	Week 52 through week 78
Incidence of Adverse Event	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 through Week 52	Anytime Post Baseline through Week 52
Incidence of Antidrug Antibodies (ADAs) in the Transition Period	Number of patients with confirmed positive antidrug antibodies (ADAs) at Week 65	Anytime in Week 52 through Week 78
Percent Change From Baseline in Femoral Neck BMD at 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	Baseline through Week 52
Percent Change From Baseline in Total Hip BMD at 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	Baseline through Week 52
Number of TEAEs Leading to Patient Withdraw From the Study	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.	Main Treatment Period = Baseline-Week 52; Transition period = Week 52-78
Local Tolerability at Injection Site	Number of patients who report Injection Site Reactions at Day 1, Week 26, or Week 52.	Main Treatment Period = Day 1 & Week 26; Transition Treatment Period = Week 52

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA
• Collaborators: Teva Branded Pharmaceutical Products R&D, Inc.
• Investigators: Study Director: Teva Medical Expert, MD, Teva Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): June 19, 2023

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 25, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: TVB009-IMB-30085

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No