Osteoporosis, Postmenopausal
Conditions
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.
Interventions
COMBINATION_PRODUCTTVB-009
TVB-009 Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)
COMBINATION_PRODUCTProlia®
Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS)
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
60 Years to 90 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in LS-BMD at Week 52 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in LS-BMD at Week 26 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |
| Percent Change From Baseline in sCTX-1 at Week 26 | Baseline and week 26 | Percent change from baseline in serum C-telopeptide cross-link of type 1 collagen at week 26 |
| Difference Between Percent Change From Baseline in P1NP Between Week 52 and Week 78 | 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 | Week 52 through week 78 | Number of patients experiencing new fractures between week 52 and week 78 |
| Incidence of Adverse Event | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Difference Between Percent Change From Baseline in sCTX-1 Between Week 52 and Week 78 | 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 |
Countries
Bulgaria, Czechia, Georgia, Germany, Hungary, Poland, Russia, Slovakia, Ukraine, United States
Participant flow
Pre-assignment details
332 subjects were randomized into the study. Those that completed the Main treatment period were then randomized into the transition period. Therefore, the 3 arms noted as Transition period are the same subjects that were included in the Treatment Period.
Participants by arm
| Arm | Count |
|---|---|
| TVB-009 Main Treatment Period TVB-009 (denosumab) pre-filled syringe, administered at weeks 1 and 26
TVB-009: TVB-009 Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS) | 166 |
| PROLIA Main Treatment Period Prolia® (denosumab) pre-filled syringe, administered at weeks 1 and 26
Prolia®: Denosumab solution for injection 60 mg/mL (1 mL) prefilled syringe (PFS) | 166 |
| Total | 332 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Main Treatment Period (Week1 to Week 52) | Adverse Event | 3 | 7 | 0 | 0 | 0 |
| Main Treatment Period (Week1 to Week 52) | Multiple Other Reasons | 2 | 4 | 0 | 0 | 0 |
| Main Treatment Period (Week1 to Week 52) | Withdrawal by Subject | 13 | 12 | 0 | 0 | 0 |
| Transition Period (Week 52 to Week 78) | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Transition Period (Week 52 to Week 78) | Multiple Other Reasons | 0 | 0 | 1 | 2 | 1 |
| Transition Period (Week 52 to Week 78) | Withdrawal by Subject | 0 | 0 | 7 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | TVB-009 Main Treatment Period | PROLIA Main Treatment Period |
|---|---|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 5.63 | 68.5 years STANDARD_DEVIATION 5.69 | 67.7 years STANDARD_DEVIATION 5.56 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 41 Participants | 23 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 291 Participants | 143 Participants | 148 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Previous Use of Biophosphonates No | 290 Participants | 145 Participants | 145 Participants |
| Previous Use of Biophosphonates Yes | 42 Participants | 21 Participants | 21 Participants |
| Prior Fractures No | 257 Participants | 129 Participants | 128 Participants |
| Prior Fractures Yes | 75 Participants | 37 Participants | 38 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 329 Participants | 165 Participants | 164 Participants |
| Region of Enrollment Bulgaria | 42 participants | 22 participants | 20 participants |
| Region of Enrollment Czechia | 40 participants | 21 participants | 19 participants |
| Region of Enrollment Georgia | 26 participants | 17 participants | 9 participants |
| Region of Enrollment Germany | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Hungary | 17 participants | 11 participants | 6 participants |
| Region of Enrollment Poland | 67 participants | 30 participants | 37 participants |
| Region of Enrollment Russia | 25 participants | 11 participants | 14 participants |
| Region of Enrollment Slovakia | 19 participants | 6 participants | 13 participants |
| Region of Enrollment Ukraine | 25 participants | 13 participants | 12 participants |
| Region of Enrollment United States | 69 participants | 34 participants | 35 participants |
| Sex: Female, Male Female | 332 Participants | 166 Participants | 166 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Taking Calcium & Vitamin D Supplements No | 19 Participants | 9 Participants | 10 Participants |
| Taking Calcium & Vitamin D Supplements Yes | 56 Participants | 28 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 166 | 0 / 165 | 0 / 148 | 0 / 72 | 0 / 71 |
| other Total, other adverse events | 123 / 166 | 108 / 165 | 42 / 148 | 20 / 72 | 11 / 71 |
| serious Total, serious adverse events | 8 / 166 | 6 / 165 | 5 / 148 | 0 / 72 | 1 / 71 |
Outcome results
Primary
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
Time frame: Baseline and week 52
Population: The mITT population was used for this analysis. The modified intent-to-treat (mITT) analysis set will include all randomized patients who received at least 1 dose of IMP and had at least 1 post-baseline evaluation of LS-BMD
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Baseline in LS-BMD at Week 52 | 4.76 percentage of change from baseline |
| PROLIA Main Treatment Period | Percent Change From Baseline in LS-BMD at Week 52 | 4.54 percentage of change from baseline |
Comparison: LS means, differences and confidence intervals (CI) from the ANCOVA model with percent change from baseline to Week 52 in LS-BMD as the outcome, treatment group, region and previous use of bisphosphates as fixed effects, baseline LS-BMD and baseline weight as covariates. Missing outcomes imputed using multiple imputation methods under the MAR assumption.95% CI: [-0.73, 1.15]
Secondary
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.
Time frame: Baseline, Week 52, Week 78
Population: TmITT population was used. The transition modified intent-to-treat (TmITT) analysis set will include all patients who received the third dose of IMP and had an end-of-study evaluation of LS-BMD.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Difference Between Percent Change From Baseline in P1NP Between Week 52 and Week 78 | 3.95 Percent change | Standard Deviation 23.376 |
| PROLIA Main Treatment Period | Difference Between Percent Change From Baseline in P1NP Between Week 52 and Week 78 | 4.83 Percent change | Standard Deviation 14.551 |
| PROLIA Main / TVB-009 Transition Period | Difference Between Percent Change From Baseline in P1NP Between Week 52 and Week 78 | 2.89 Percent change | Standard Deviation 39.804 |
Secondary
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
Time frame: Baseline, Week 52, Week 78
Population: TmITT population was used. The transition modified intent-to-treat (TmITT) analysis set will include all patients who received the third dose of IMP and had an end-of-study evaluation of LS-BMD.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Difference Between Percent Change From Baseline in sCTX-1 Between Week 52 and Week 78 | 9.95 Percent change from baseline | Standard Deviation 41.612 |
| PROLIA Main Treatment Period | Difference Between Percent Change From Baseline in sCTX-1 Between Week 52 and Week 78 | 13.17 Percent change from baseline | Standard Deviation 28.558 |
| PROLIA Main / TVB-009 Transition Period | Difference Between Percent Change From Baseline in sCTX-1 Between Week 52 and Week 78 | 7.55 Percent change from baseline | Standard Deviation 36.509 |
Secondary
Incidence of Adverse Event
Number of patients reporting at least one treatment-emergent adverse event up to week 52
Time frame: Up to week 52
Population: Safety Analysis Set (SAS) was used. The safety analysis set will include all randomized patients who received at least 1 dose of IMP.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TVB-009 Main Treatment Period | Incidence of Adverse Event | TEAE Not Related to Study Drug | 104 Participants |
| TVB-009 Main Treatment Period | Incidence of Adverse Event | TEAE Related to Study Drug | 19 Participants |
| TVB-009 Main Treatment Period | Incidence of Adverse Event | No TEAEs Reported | 43 Participants |
| TVB-009 Main Treatment Period | Incidence of Adverse Event | TEAE Related to Medical Device | 0 Participants |
| PROLIA Main Treatment Period | Incidence of Adverse Event | No TEAEs Reported | 57 Participants |
| PROLIA Main Treatment Period | Incidence of Adverse Event | TEAE Related to Study Drug | 13 Participants |
| PROLIA Main Treatment Period | Incidence of Adverse Event | TEAE Not Related to Study Drug | 95 Participants |
| PROLIA Main Treatment Period | Incidence of Adverse Event | TEAE Related to Medical Device | 0 Participants |
Secondary
Incidence of Adverse Events in the Transition Period
Number of patients reporting at least one treatment-emergent adverse event between weeks 52 and 78
Time frame: Week 52 through week 78
Population: Transition Safety Analysis Set was used. The transition safety analysis set will include all patients who received the third dose of the IMP.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TVB-009 Main Treatment Period | Incidence of Adverse Events in the Transition Period | TEAE Related to Medical Device | 0 Participants |
| TVB-009 Main Treatment Period | Incidence of Adverse Events in the Transition Period | No TEAE Reported | 98 Participants |
| TVB-009 Main Treatment Period | Incidence of Adverse Events in the Transition Period | TEAE Not Related to Study Drug | 48 Participants |
| TVB-009 Main Treatment Period | Incidence of Adverse Events in the Transition Period | TEAE Related to Study Drug | 2 Participants |
| PROLIA Main Treatment Period | Incidence of Adverse Events in the Transition Period | TEAE Not Related to Study Drug | 20 Participants |
| PROLIA Main Treatment Period | Incidence of Adverse Events in the Transition Period | No TEAE Reported | 52 Participants |
| PROLIA Main Treatment Period | Incidence of Adverse Events in the Transition Period | TEAE Related to Medical Device | 0 Participants |
| PROLIA Main Treatment Period | Incidence of Adverse Events in the Transition Period | TEAE Related to Study Drug | 0 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Adverse Events in the Transition Period | No TEAE Reported | 45 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Adverse Events in the Transition Period | TEAE Related to Study Drug | 0 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Adverse Events in the Transition Period | TEAE Not Related to Study Drug | 26 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Adverse Events in the Transition Period | TEAE Related to Medical Device | 0 Participants |
Secondary
Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period
Number of patients with confirmed positive antidrug antibodies (ADAs) post-baseline through Week 52
Time frame: Anytime Post Baseline through Week 52
Population: The Safety Analysis Set was used. The safety analysis set will include all randomized patients who received at least 1 dose of IMP.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | ADA Status | Positive | 11 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | ADA Status | Positive, Not Treatment Related | 8 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | ADA Status | Negative | 147 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | Neutralizing ADA Status Among Positive | Positive | 1 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | Neutralizing ADA Status Among Positive | Positive, Not Treatment Related | 0 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | Neutralizing ADA Status Among Positive | Negative | 10 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | Neutralizing ADA Status Among Positive | Positive, Not Treatment Related | 0 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | ADA Status | Positive | 25 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | Neutralizing ADA Status Among Positive | Positive | 2 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | ADA Status | Positive, Not Treatment Related | 11 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | Neutralizing ADA Status Among Positive | Negative | 23 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Main Treatment Period | ADA Status | Negative | 129 Participants |
Secondary
Incidence of Antidrug Antibodies (ADAs) in the Transition Period
Number of patients with confirmed positive antidrug antibodies (ADAs) at Week 65
Time frame: Anytime in Week 52 through Week 78
Population: The Transition Safety Analysis Set was used. The transition safety analysis set will include all patients who received the third dose of the IMP.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | ADA Status | Positive | 7 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | ADA Status | Positive, Not Treatment Related | 7 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | ADA Status | Negative | 133 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | Neutralizing ADA Status Among Positive | Positive | 1 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | Neutralizing ADA Status Among Positive | Positive, Not Treatment Related | 0 Participants |
| TVB-009 Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | Neutralizing ADA Status Among Positive | Negative | 6 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | Neutralizing ADA Status Among Positive | Negative | 5 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | ADA Status | Positive | 5 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | Neutralizing ADA Status Among Positive | Positive | 0 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | Neutralizing ADA Status Among Positive | Positive, Not Treatment Related | 0 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | ADA Status | Positive, Not Treatment Related | 4 Participants |
| PROLIA Main Treatment Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | ADA Status | Negative | 61 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | ADA Status | Positive, Not Treatment Related | 1 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | ADA Status | Negative | 65 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | Neutralizing ADA Status Among Positive | Negative | 4 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | Neutralizing ADA Status Among Positive | Positive | 0 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | ADA Status | Positive | 4 Participants |
| PROLIA Main / TVB-009 Transition Period | Incidence of Antidrug Antibodies (ADAs) in the Transition Period | Neutralizing ADA Status Among Positive | Positive, Not Treatment Related | 0 Participants |
Secondary
Local Tolerability at Injection Site
Number of patients who report Injection Site Reactions at Day 1, Week 26, or Week 52.
Time frame: Main Treatment Period = Day 1 & Week 26; Transition Treatment Period = Week 52
Population: Safety Analysis Set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Erythema | 2 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Ecchymosis | 4 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Ecchymosis | 3 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Swelling | 2 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Induration | 2 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Erythema | 5 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Tenderness | 1 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Tenderness | 3 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Warmth | 0 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Pain | 6 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Swelling | 1 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Induration | 2 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Pain | 7 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Day 1 | No Reaction | 144 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Week 26 | No Reaction | 142 Participants |
| TVB-009 Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Warmth | 0 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Induration | 0 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Erythema | 4 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Ecchymosis | 2 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Induration | 3 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Tenderness | 4 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Warmth | 1 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Swelling | 1 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Day 1 | Pain | 5 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Day 1 | No Reaction | 145 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Erythema | 4 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Ecchymosis | 0 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Tenderness | 1 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Warmth | 1 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Swelling | 1 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Week 26 | Pain | 4 Participants |
| PROLIA Main Treatment Period | Local Tolerability at Injection Site | Week 26 | No Reaction | 142 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Erythema | 2 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Ecchymosis | 3 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Induration | 3 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Tenderness | 1 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Warmth | 0 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Swelling | 0 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Pain | 6 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | No Reaction | 133 Participants |
| PROLIA Main / PROLIA Transition Period | Local Tolerability at Injection Site | Week 52 | Induration | 3 Participants |
| PROLIA Main / PROLIA Transition Period | Local Tolerability at Injection Site | Week 52 | Pain | 4 Participants |
| PROLIA Main / PROLIA Transition Period | Local Tolerability at Injection Site | Week 52 | Tenderness | 1 Participants |
| PROLIA Main / PROLIA Transition Period | Local Tolerability at Injection Site | Week 52 | Warmth | 2 Participants |
| PROLIA Main / PROLIA Transition Period | Local Tolerability at Injection Site | Week 52 | Swelling | 1 Participants |
| PROLIA Main / PROLIA Transition Period | Local Tolerability at Injection Site | Week 52 | Erythema | 2 Participants |
| PROLIA Main / PROLIA Transition Period | Local Tolerability at Injection Site | Week 52 | Ecchymosis | 0 Participants |
| PROLIA Main / PROLIA Transition Period | Local Tolerability at Injection Site | Week 52 | No Reaction | 59 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Induration | 0 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Ecchymosis | 1 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Erythema | 2 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Tenderness | 1 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Pain | 3 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Swelling | 1 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | Warmth | 0 Participants |
| PROLIA Main / TVB-009 Transition Period | Local Tolerability at Injection Site | Week 52 | No Reaction | 63 Participants |
Secondary
Number of Fractures up to Week 52
Number of patients with who experienced any new fractures up to week 52.
Time frame: Up to week 52
Population: mITT population was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TVB-009 Main Treatment Period | Number of Fractures up to Week 52 | 3 number participants with fractures |
| PROLIA Main Treatment Period | Number of Fractures up to Week 52 | 5 number participants with fractures |
Secondary
Number of Patients With Fractures Between Week 52 and Week 78
Number of patients experiencing new fractures between week 52 and week 78
Time frame: Week 52 through week 78
Population: TmITT population was used. The transition modified intent-to-treat (TmITT) analysis set will include all patients who received the third dose of IMP and had an end-of-study evaluation of LS-BMD.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TVB-009 Main Treatment Period | Number of Patients With Fractures Between Week 52 and Week 78 | 1 Number participants with fractures |
| PROLIA Main Treatment Period | Number of Patients With Fractures Between Week 52 and Week 78 | 0 Number participants with fractures |
| PROLIA Main / TVB-009 Transition Period | Number of Patients With Fractures Between Week 52 and Week 78 | 1 Number participants with fractures |
Secondary
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.
Time frame: Main Treatment Period = Baseline-Week 52; Transition period = Week 52-78
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TVB-009 Main Treatment Period | Number of TEAEs Leading to Patient Withdraw From the Study | 3 Participants |
| PROLIA Main Treatment Period | Number of TEAEs Leading to Patient Withdraw From the Study | 7 Participants |
| PROLIA Main / TVB-009 Transition Period | Number of TEAEs Leading to Patient Withdraw From the Study | 0 Participants |
| PROLIA Main / PROLIA Transition Period | Number of TEAEs Leading to Patient Withdraw From the Study | 0 Participants |
| PROLIA Main / TVB-009 Transition Period | Number of TEAEs Leading to Patient Withdraw From the Study | 0 Participants |
Secondary
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
Time frame: Week 4
Population: mITT population was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TVB-009 Main Treatment Period | Percentage of Participatns With sCTX-1 Suppression at Week 4 | 94.2 Percentage of participants |
| PROLIA Main Treatment Period | Percentage of Participatns With sCTX-1 Suppression at Week 4 | 94.0 Percentage of participants |
Secondary
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
Time frame: Baseline, week 26
Population: mITT population was used for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Baseline in Femoral Neck BMD at Week 26 | 1.87 percentage of change from baseline | Standard Deviation 4.877 |
| PROLIA Main Treatment Period | Percent Change From Baseline in Femoral Neck BMD at Week 26 | 2.01 percentage of change from baseline | Standard Deviation 3.611 |
Secondary
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
Time frame: Baseline through Week 52
Population: mITT population was used for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Baseline in Femoral Neck BMD at Week 52 | 2.39 Percent change from baseline | Standard Deviation 5.795 |
| PROLIA Main Treatment Period | Percent Change From Baseline in Femoral Neck BMD at Week 52 | 2.34 Percent change from baseline | Standard Deviation 3.78 |
Secondary
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
Time frame: Baseline and week 26
Population: The mITT population was used in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Baseline in LS-BMD at Week 26 | 3.70 percentage of change from baseline | Standard Deviation 4.294 |
| PROLIA Main Treatment Period | Percent Change From Baseline in LS-BMD at Week 26 | 3.62 percentage of change from baseline | Standard Deviation 3.815 |
Secondary
Percent Change From Baseline in P1NP
Percent change from baseline in procollagen type 1 N propeptide (P1NP) to Week 52
Time frame: Baseline through Week 52
Population: mITT population was used for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Baseline in P1NP | -56.43 percentage of change from baseline | Standard Deviation 35.431 |
| PROLIA Main Treatment Period | Percent Change From Baseline in P1NP | -62.03 percentage of change from baseline | Standard Deviation 33.712 |
Secondary
Percent Change From Baseline in sCTX-1
Percent change from baseline in serum C-telopeptide cross-link of type 1 collagen
Time frame: Baseline through Week 52
Population: mITT population was used for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Baseline in sCTX-1 | -57.91 percentage of change from baseline | Standard Deviation 44.161 |
| PROLIA Main Treatment Period | Percent Change From Baseline in sCTX-1 | -68.80 percentage of change from baseline | Standard Deviation 35.846 |
Secondary
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
Time frame: Baseline and week 26
Population: The mITT was used for this analysis. The modified intent-to-treat (mITT) analysis set includes all randomized patients who received at least 1 dose of IMP and had at least 1 post-baseline evaluation of LS-BMD
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Baseline in sCTX-1 at Week 26 | -56.05 percentage of change from baseline |
| PROLIA Main Treatment Period | Percent Change From Baseline in sCTX-1 at Week 26 | -65.13 percentage of change from baseline |
Comparison: LS means, differences and confidence intervals (CI) from the ANCOVA model with percent change from baseline to Week 26 in sCTX-1 as the outcome, treatment group, region and previous use of bisphosphates as fixed effects, baseline sCTX-1 and baseline weight as covariates. Missing outcomes are not imputed. Results below the limit of quantification (BLQ) are imputed as the low limit of quantification (LLOQ = 0.033 ng/mL).95% CI: [-0.14, 18.29]
Secondary
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
Time frame: Baseline, week 26
Population: mITT population was used for the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Baseline in Total Hip BMD at Week 26 | 1.89 percentage of change from baseline | Standard Deviation 3.488 |
| PROLIA Main Treatment Period | Percent Change From Baseline in Total Hip BMD at Week 26 | 2.02 percentage of change from baseline | Standard Deviation 2.526 |
Secondary
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
Time frame: Baseline through Week 52
Population: mITT population was used for the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Baseline in Total Hip BMD at Week 52 | 2.67 Percent change from baseline | Standard Deviation 3.981 |
| PROLIA Main Treatment Period | Percent Change From Baseline in Total Hip BMD at Week 52 | 3.00 Percent change from baseline | Standard Deviation 2.768 |
Secondary
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
Time frame: Week 52 through week 78
Population: TmITT population was used. The transition modified intent-to-treat (TmITT) analysis set will include all patients who received the third dose of IMP and had an end-of-study evaluation of LS-BMD.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Week 52 in Femoral Neck BMD by DXA at Week 78 | 0.38 Percent change from week 52 | Standard Deviation 3.525 |
| PROLIA Main Treatment Period | Percent Change From Week 52 in Femoral Neck BMD by DXA at Week 78 | 0.80 Percent change from week 52 | Standard Deviation 3.56 |
| PROLIA Main / TVB-009 Transition Period | Percent Change From Week 52 in Femoral Neck BMD by DXA at Week 78 | 0.94 Percent change from week 52 | Standard Deviation 3.082 |
Secondary
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
Time frame: Week 52 through week 78
Population: TmITT population was used. The transition modified intent-to-treat (TmITT) analysis set will include all patients who received the third dose of IMP and had an end-of-study evaluation of LS-BMD.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Week 52 in LS-BMD by DXA at Week 78 | 0.82 percentage of change from baseline | Standard Deviation 3.12 |
| PROLIA Main Treatment Period | Percent Change From Week 52 in LS-BMD by DXA at Week 78 | 1.15 percentage of change from baseline | Standard Deviation 3.44 |
| PROLIA Main / TVB-009 Transition Period | Percent Change From Week 52 in LS-BMD by DXA at Week 78 | 1.24 percentage of change from baseline | Standard Deviation 3.069 |
Secondary
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
Time frame: Week 52 through week 78
Population: TmITT population was used. The transition modified intent-to-treat (TmITT) analysis set will include all patients who received the third dose of IMP and had an end-of-study evaluation of LS-BMD.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TVB-009 Main Treatment Period | Percent Change From Week 52 in Total Hip BMD by DXA at Week 78 | 0.01 Percent change from week 52 | Standard Deviation 2.089 |
| PROLIA Main Treatment Period | Percent Change From Week 52 in Total Hip BMD by DXA at Week 78 | 0.66 Percent change from week 52 | Standard Deviation 2.109 |
| PROLIA Main / TVB-009 Transition Period | Percent Change From Week 52 in Total Hip BMD by DXA at Week 78 | 0.27 Percent change from week 52 | Standard Deviation 2.264 |