A Study to Test if TVB-009P is Effective in Relieving Postmenopausal Osteoporosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test if TVB-009P is Effective in Relieving Postmenopausal Osteoporosis (NCT04729621), a randomized phase 3 study. The primary outcome is Percent Change From Baseline in LS-BMD at Week 52.

2. Clinical Question

The trial's stated purpose was to demonstrate similar efficacy and safety between TVB-009 and Prolia®. Its primary outcome was a continuous measurement: the percent change in lumbar spine bone mineral density from baseline to week 52. A continuous outcome retains information about the magnitude of change rather than reducing each participant's result to a category. The registry also lists bone-density outcomes at other skeletal sites and time points, measures of bone-turnover markers, and fractures through week 52. The primary comparison is specifically about the average bone-density change in the defined analysis population; it does not by itself answer every question about the other outcomes or all possible patient groups.

3. Trial Design

This was a phase 3, randomized, double-blind, multinational, multicenter, parallel-group study sponsored by Teva Pharmaceuticals USA. The registry lists quadruple masking. Enrollment was 332, and the study status is completed. The recorded study start was 2021-03-22, and primary completion was 2022-12-31. Details about the countries and sites are not reported in the registry record.

The main treatment comparison was between TVB-009 and Prolia® (denosumab). Both were described as pre-filled syringes administered at weeks 1 and 26. A transition period included a week-52 administration: patients randomized to TVB-009 in the main period received TVB-009, while the Prolia® main-period group included those who received Prolia® and those who changed to TVB-009. The registry record lists these treatment pathways but does not report the rationale for the transition assignments or further details of allocation procedures.

The primary endpoint was assessed at week 52. Its analysis was based on the modified intent-to-treat population, defined as randomized patients who received at least 1 dose of investigational medicinal product and had at least 1 post-baseline lumbar spine bone mineral density evaluation. The record reports 157.0 participants for the TVB-009 main-treatment arm and 152.0 for the Prolia® main-treatment arm in the primary outcome. These outcome counts need not match total enrollment because the registry describes a defined analysis population and endpoint-specific data.

The registry identifies the study as randomized and double-blind, but further operational details, including how masking was maintained, are not reported in the registry record. The allocation ratio, planned sample-size justification, and specific statistical model are also not reported in the registry record. The study's stated purpose was to compare efficacy, safety, and immunogenicity; the posted results summarized in this analysis include the primary bone-density result, selected secondary outcomes, and adverse-event counts.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 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".

Main Treatment Period (Week1 to Week 52)

Reasons for not completing this period:

Transition Period (Week 52 to Week 78)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 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

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The baseline characteristics are only presented for the Treatment Period Arms as the same subject were employed in the Transition Period.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline in LS-BMD at Week 52, measured over Baseline and week 52.

The primary endpoint was percent change from baseline in lumbar spine bone mineral density at week 52, based on centrally assessed dual energy X ray absorptiometry. It expresses the change in a continuous measure of bone density relative to each participant's baseline measurement. The registry reports the outcome as a least-squares mean with a 95% confidence interval.

Bone mineral density is used in this trial as an efficacy measure because the study's central comparison concerns changes in bone density during treatment. Measuring change from baseline focuses the endpoint on within-participant change over the study period, while comparing the groups addresses whether their average changes differ. Central assessment describes how the DXA measurements were assessed; the detailed procedures and quality-control methods are not reported in the registry record.

A least-squares mean is a model-based estimate of a group mean. Such estimates can account for specified variables in an analysis model, but the variables and model used for this endpoint are not reported in the registry record. The endpoint should therefore be read as the posted group estimates and their uncertainty, rather than as evidence about unreported modeling choices. It also measures bone-density change, not fractures, symptoms, or every aspect of safety. Those outcomes require separate assessment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry reports least-squares means with 95% confidence intervals for each treatment group. A mean gives a summary of the observed outcome distribution, while a confidence interval conveys uncertainty around the estimated mean. In general, a confidence interval is not a guarantee that the true value lies within the particular interval; it is an interval produced by a method designed to have the stated coverage over repeated use under its assumptions. The registry does not report enough detail to assess every assumption of the primary model.

A least-squares mean is generally a mean estimated from a statistical model, rather than necessarily the raw arithmetic average. Models can adjust for prespecified factors, but which factors were included, how missing observations were handled, and what model form was used for the primary endpoint are not reported in the registry record. The registry identifies the analysis population and the summary measure, but those details alone do not fully reproduce the analysis.

The primary comparison is reported as a net mean difference with a 95% confidence interval. A difference estimate is useful because it directly expresses the contrast between groups on the endpoint's scale. The interval extending from -0.73 to 1.15 includes zero, which represents no difference on that scale. This observation is not equivalent to proof that the groups are equivalent. A nonsignificant or imprecise difference does not establish similarity: equivalence requires the interval or an associated test to meet a prespecified margin. The margin and test details are not reported in the registry record.

Equivalence and superiority ask different statistical questions. A superiority analysis typically asks whether the data support a difference in a specified direction or any difference, depending on the test. An equivalence analysis asks whether the data are sufficiently precise to rule out differences outside a pre-established acceptable range. The acceptable range must be chosen before examining the results and justified for the endpoint. It is not reported in the registry record, so readers cannot use the reported interval to confirm whether the equivalence criterion was satisfied.

The secondary outcome comparisons include simple unadjusted recalculations from posted summary statistics. For a continuous outcome, such a recalculation can estimate a difference in group means and its uncertainty using the group sample sizes and variability measures. It is not a replacement for a trial's planned analysis: it may not account for covariates, repeated measurements, stratification, or other features of the original model. The specific methods used for the sponsor's secondary analyses are not reported in the registry record. The posted recalculations should therefore be understood as descriptive checks based on the available summaries, not as a reconstruction of the full analysis.

The p-values associated with the secondary recalculations are unadjusted. A p-value describes how compatible the observed data are with a specified null model under the test assumptions; it is not the probability that the null hypothesis is true, nor a measure of the size or importance of an effect. When several outcomes are examined, the chance of at least one apparently unusual result can increase. Adjustment procedures or a prespecified hierarchy can address multiplicity, but the relevant plan is not reported in the registry record. For that reason, individual unadjusted secondary results should be treated as exploratory rather than as stand-alone confirmation.

Planning illustrations based on observed effects answer a different question from the trial's results. They show how sample sizes might vary under stated assumptions if a chosen fraction of an observed effect were to be targeted. These are planning illustrations, not observed power, and they do not establish what the trial was designed to detect. The registry record's illustration assumptions include a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as stated fractions of observed effects. The trial's own sample-size assumptions and justification are not reported in the registry record. Because observed effects can be unstable, especially when estimates are imprecise, such illustrations should not be read as evidence that a study was adequately powered for a particular clinical objective.

Missing-data handling matters because the primary analysis set required a post-baseline evaluation. Participants without such an evaluation are not included in the registry's stated mITT definition. The number excluded, the reasons for missing measurements, and the methods used to address missing data are not reported in the registry record. If missingness is related to treatment or outcome, estimates from observed measurements can differ from those that would have been obtained with complete follow-up. The available record does not permit assessment of that possibility.

Over-dispersion is a concern for outcomes whose variability is larger than assumed by a statistical model. In general, failing to account for over-dispersion can make uncertainty estimates too small and statistical evidence appear stronger than warranted. The primary endpoint is continuous, and the registry does not report whether over-dispersion was assessed or relevant to the model. This is a general statistical consideration, not a claim that over-dispersion occurred in this trial.

10. Analyses Reported by the Sponsor

The primary result posted in the registry is the sponsor-reported analysis: least-squares mean percent changes of 4.76 for TVB-009 and 4.54 for Prolia®, with a reported net mean difference of 0.21 and a 95% confidence interval from -0.73 to 1.15. The registry labels that comparison as an equivalence analysis. It does not report a p-value, the equivalence margin, or enough detail about the model and testing procedure to verify the equivalence decision independently.

The recalculated comparisons in the secondary-outcome material are unadjusted calculations from posted summary statistics. They are not a substitute for the sponsor's full analysis, which may use modeling details that are not in the registry record. No discrepancy is flagged between a sponsor result and a recalculation in the posted material. For the primary endpoint, no separate recalculated comparison is reported; the interpretation therefore rests on the registry's reported estimates and their stated confidence intervals.

The central issue is not a numerical conflict but the limited detail available to assess the stated equivalence conclusion. The reported estimate and interval describe the comparison, while the missing margin and test details prevent an independent determination of whether the prespecified equivalence standard was met. The registry record does not report additional analysis documentation that would resolve that uncertainty.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 23 outcome measures and reports 22 secondary outcomes. It does not report a statistical analysis plan describing how the primary and secondary endpoints were ordered, whether any secondary outcomes were confirmatory, or how multiplicity was addressed. Multiplicity arises when several hypotheses are examined: even if no underlying effects exist, repeated testing can produce apparently notable results by chance. A prespecified testing hierarchy or adjustment method can control that risk, but neither is described in the registry record. Consequently, unadjusted secondary p-values should not be interpreted as if they were the result of a single isolated test.

The primary comparison is identified as an equivalence analysis, but the equivalence margin and the method used to assess it are not reported in the registry record. Those details are central to interpreting the primary claim. The record also does not report interim analyses or stopping rules, so no conclusions can be drawn about whether results were reviewed during the study or whether any interim procedure affected the analysis.

The primary population was the modified intent-to-treat set: randomized patients who received at least 1 dose of investigational medicinal product and had at least 1 post-baseline lumbar spine bone mineral density evaluation. This definition excludes randomized participants without the specified exposure or evaluation. The number of randomized participants excluded from the primary analysis and the reasons for exclusion are not reported in the registry record. Counts of participants contributing data at individual secondary time points vary, but the record does not provide a full account of missing observations or endpoint-specific exclusions.

Methods for handling missing outcomes, including any imputation or sensitivity analyses, are not reported in the registry record. Without those details, it is not possible to determine whether the analysis depends on assumptions about why measurements are missing or how the results would change under alternative assumptions. The statistical model, covariate adjustments, and detailed analysis populations for the primary and secondary outcomes are also not reported. These omissions do not establish that a particular problem occurred; they limit independent assessment of robustness and the strength of confirmatory claims.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cholelithiasis (1.4%), covid-19 pneumonia (0.7%), malaise (0.7%), helicobacter infection (0.7%), bone cancer (0.7%).

For the main treatment period, the registry reports serious adverse events in 8 of 166 participants at risk in the TVB-009 group and 6 of 165 participants at risk in the Prolia® group. In the transition-period groups, serious adverse events were reported in 5 of 148 participants continuing TVB-009, 0 of 72 continuing Prolia®, and 1 of 71 changing from Prolia® to TVB-009. No deaths were reported in these groups.

These are group counts over the registry's recorded safety periods. The transition groups represent different treatment paths and should not be read as a simple continuation of the randomized main-period comparison. The record does not provide enough detail about follow-up time, event adjudication, or statistical comparisons to infer relative risks or make a formal between-group safety claim. It also does not establish whether an event was caused by treatment.

The listed serious adverse event terms include cholelithiasis at 1.4%, and COVID-19 pneumonia, malaise, Helicobacter infection, bone cancer, and urinary incontinence at 0.7% each. These terms and percentages describe the posted serious-event listings; they do not show the full clinical context for each event. The record also reports other adverse events, but a count of participants with an event is not a measure of severity or causality. Safety interpretation should remain descriptive given the information reported.

13. What the Result Does, and Does Not, Mean

The primary estimates show similar-sized reported average changes in lumbar spine bone mineral density in the two main-treatment groups at week 52. The estimated net mean difference was 0.21, and its 95% confidence interval ranged from -0.73 to 1.15. This interval expresses uncertainty around the difference and includes no difference. The registry classifies the analysis as equivalence, but the equivalence margin and testing procedure are not reported in the registry record. Therefore, the posted figures allow readers to describe the estimate and precision, but not independently verify that the study met its equivalence criterion.

This is not the same as concluding that the treatments are identical. An estimate close to zero can arise when true differences are small, but it can also be imprecise. Equivalence requires evidence that the plausible differences lie within a prespecified acceptable range. That range is not available in the registry record. Conversely, the confidence interval is not evidence that a clinically important difference occurred; the record does not report a clinical importance threshold against which the interval can be judged.

The result is specific to the primary endpoint, its week-52 assessment, and the modified intent-to-treat population described in the record. It does not establish an effect on fractures, every bone-turnover marker, other skeletal sites, long-term outcomes, or all patient groups. Secondary outcomes can add context, but their unadjusted status and the absence of a reported multiplicity plan limit the weight they can carry as confirmatory evidence.

The safety counts are also descriptive. They report how many participants experienced serious adverse events in the listed groups, but do not by themselves establish comparative safety or causation. No deaths were reported in those groups, but that observation does not answer every safety question. Overall, the registry contains useful estimates and counts; its limited reporting of margins, analysis details, missing-data handling, and multiplicity constrains the conclusions that can be independently drawn.

14. Why This Trial Matters Statistically

This trial illustrates why a comparison labeled as equivalence needs more than similar point estimates. A reader needs the estimated contrast and its uncertainty, but also the prespecified margin that defines how much difference would still count as equivalent. The registry reports the contrast and confidence interval but not the margin. That omission is statistically important because the same interval could support or fail an equivalence conclusion depending on the acceptable range set in advance.

The endpoint also shows the distinction between a group mean and a between-group comparison. Each treatment group's least-squares mean describes estimated change within that group. The net mean difference directly addresses the comparative question, and its confidence interval conveys uncertainty about that contrast. Looking only at the group estimates, or comparing their separate confidence intervals informally, is not a substitute for interpreting the reported difference and its interval.

The study's modified intent-to-treat definition is another important feature. It includes randomized patients who received at least 1 dose and had at least 1 post-baseline evaluation, so it is not simply every randomized participant. Clear reporting of the number excluded, missing observations, and sensitivity analyses would help readers assess how population selection could affect the result. Those details are not reported in the registry record.

Finally, the range of secondary outcomes demonstrates the value and the interpretive challenge of measuring several related outcomes. Bone density at different sites, turnover markers, and fractures do not answer exactly the same question. Without a reported multiplicity plan, secondary results require restraint, even when they appear consistent with the primary pattern. Statistically, this record is a useful example of how effect estimates, uncertainty, analysis populations, and missing protocol details all contribute to a careful reading—not just the point estimate or the study's stated objective.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific reporting gaps limit independent interpretation. Most importantly, the primary analysis is labeled as equivalence, but the equivalence margin, test procedure, and p-value are not reported in the registry record. The primary model is described through its least-squares mean summary, but the model specification and any covariate adjustments are not reported. These omissions prevent readers from fully reproducing or evaluating the primary inference.

The modified intent-to-treat population requires both treatment exposure and a post-baseline evaluation. The number of randomized participants who did not meet that definition, why they were excluded, and how missing outcome data were handled are not reported in the registry record. This limits assessment of whether the analyzed participants represent the randomized groups and whether alternative missing-data assumptions would change the findings.

The registry does not report the study's sample-size justification or its planned detectable effect. Planning illustrations based on observed effects are not a substitute for those design details and should not be treated as observed power. Allocation ratio, randomization procedures, and additional details about masking are also not reported. The record identifies the study as randomized, double-blind, and quadruple-masked, but does not supply operational details needed to assess how those features were implemented.

Multiplicity handling for the many outcomes is not reported, and no interim-analysis plan is described. The record lists 23 outcome measures and posts 22 secondary outcomes, without stating why results for every listed measure are not available. Safety reporting gives counts and selected serious-event terms, but the information does not provide full event narratives, follow-up context, or formal comparative analyses. These are limitations of what can be established from the registry record; they do not demonstrate that the trial's conduct or analyses were deficient.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Test if TVB-009P is Effective in Relieving Postmenopausal Osteoporosis — NCT04729621.
• Registry record last updated 2026-10-01; status last verified 2026-09.
• Results first posted 2024-04-18.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT04729621 is a completed phase 3 randomized, double-blind, multinational, multicenter, parallel-group study sponsored by Teva Pharmaceuticals USA. It enrolled 332 participants with postmenopausal osteoporosis and compared TVB-009 (denosumab) with Prolia® (denosumab). The primary endpoint was percent change from baseline in lumbar spine bone mineral density at week 52, analyzed in a modified intent-to-treat population.

The reported least-squares mean changes were 4.76 for TVB-009 and 4.54 for Prolia®, with a net mean difference of 0.21 and a 95% confidence interval from -0.73 to 1.15. The registry describes the comparison as equivalence, but the equivalence margin and testing details are not reported in the registry record. Secondary bone-density, bone-turnover, fracture, and safety outcomes provide additional descriptive information, with limitations from unreported multiplicity and missing-data methods.