Study of Efficacy, Safety and Tolerability of AIN457 in Patients With Active Overuse Tendinopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Efficacy, Safety and Tolerability of AIN457 in Patients With Active Overuse Tendinopathy (NCT03344640), a randomized phase 2 study. The primary outcome is The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients - Statistical Analysis Results of Total WORC Scores at Week 14.

2. Clinical Question

3. Trial Design

The registry identifies NCT03344640 as a randomized, parallel-group, Phase II study of AIN457, or secukinumab, for active overuse tendinopathy. The official title describes a 24-week study, while the treatment-arm descriptions specify subcutaneous secukinumab 300 mg or subcutaneous placebo for 12 weeks. The primary endpoint is measured at Week 14 (Day 99). The record does not explain the relationship between the stated study duration, treatment duration, and endpoint timing beyond those descriptions.

The study title describes the trial as double-blind, while the registry masking field says quadruple. Both describe masking, but the record does not identify the masked roles or explain the difference. The brief summary describes the study as multicenter. The allocation is randomized and the model is parallel, meaning participants were assigned to one of the treatment groups rather than crossing between treatments according to the listed design.

The registry enrollment field reports 96. Separately, the brief summary says 98 patients were randomized. These figures do not match, and the registry record does not explain the discrepancy. The primary outcome uses 47 participants in the secukinumab group and 41 in the placebo group in the PD Analysis Set. Those outcome-set counts are not interchangeable with the enrollment or randomized figures.

The sponsor is Novartis Pharmaceuticals, and the study status is completed. The listed primary completion date is 2019-08-02; the study start date is 2017-12-15. The registry record does not report the protocol’s sample-size justification, the details of sequence generation or allocation concealment, or a full statistical analysis plan. Those omissions limit what can be inferred about planned design choices from the record alone.

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: 2 patients were not dosed, one patient decided to discontinue on Day 1 due to a common cold and one patient was a run-in failure

Overall Study

Reasons for not completing this period:

Follow-up Epoch

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacodynamic (PD) Analysis Set

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 safety analysis set (SAS) included all subjects that received any study drug.

6. Primary Endpoint

The registry lists the primary outcome as The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients - Statistical Analysis Results of Total WORC Scores at Week 14, measured over Week 14 (Day 99).

The primary endpoint is the total score on the Western Ontario Rotator Cuff Patient Reported Outcome measure at Week 14 (Day 99). WORC is a patient-reported measure organized into 21 items across 5 domains: Physical Symptoms, Sport/Recreation, Work Function, Lifestyle Function, and Emotional Function. The reported total and sub-scores are percentages of normal scores, with 0 representing the worst score and 100 the best.

A patient-reported measure captures the participant’s account of symptoms and functional impact rather than relying only on a clinician’s assessment. A rotator-cuff-specific measure can describe several aspects of shoulder-related experience, including symptoms and effects on daily activities, work, sport, and emotional function. This makes it relevant to a study of overuse rotator-cuff tendinopathy. These are general reasons for using a patient-reported endpoint; the registry record does not state why the investigators selected WORC over other measures.

The primary comparison concerns the total score at a specified follow-up time, not change across every assessment. Higher WORC scores indicate a better state on the scale. The registry reports group values and a least-squares mean difference for final values. It does not provide enough information to describe the detailed adjustment model, the handling of baseline values, or the clinical importance threshold for interpreting a score difference. A statistically estimated contrast therefore needs to be read alongside its confidence interval and those reporting limitations.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a between-group least-squares mean difference in final WORC values. A mean difference expresses the estimated contrast between group averages in the outcome’s original scale. A least-squares mean is generally a model-based group mean, potentially adjusted for other terms in the statistical model. Those terms and the precise model are not reported in the registry record, so the estimate should be understood as the sponsor-reported model-based contrast rather than reconstructed from the arm summaries alone.

What does the confidence interval convey?

The 90% confidence interval for the reported difference runs from -8.84 to 7.30. In general, a confidence interval shows the uncertainty associated with an estimate under a stated statistical procedure. Repeated use of a valid procedure would produce intervals that contain the target parameter at the stated coverage level at the corresponding long-run frequency. It is not a guarantee that the particular interval contains the true value, and it is not a range containing a stated proportion of individual participants’ outcomes.

For this comparison, the interval includes zero and also includes values on either side of zero. That means the data, under the reported analysis, do not tightly distinguish a small contrast from a potentially larger contrast in either direction. The interval is for the treatment difference, so it is more directly relevant to the comparative question than either group’s separate interval. The registry record does not report a clinical importance threshold, making it impossible to classify the interval’s endpoints as clinically important or unimportant using a trial-specific criterion.

How should the p-value be read?

The p-value is 0.875. In general, a p-value measures how unusual data at least as incompatible with a null hypothesis as the observed data would be, if the null hypothesis and the statistical model were correct. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of a treatment effect. A high p-value does not establish equivalence or prove that there is no effect. It indicates that the reported test does not give strong evidence against the tested null hypothesis.

The registry record labels the reported comparison as a superiority analysis. It does not report an equivalence or non-inferiority framework. Those questions require different hypotheses and, typically, prespecified margins. No such margin is reported. The estimate and interval should therefore be interpreted as a superiority comparison at the stated endpoint, not as an equivalence assessment.

Why do analysis populations matter?

The primary endpoint population is identified as the Pharmacodynamic Analysis Set. The posted arm counts for that outcome are 47 for secukinumab and 41 for placebo. A named analysis set defines which participants contribute to a particular analysis, but the registry record does not give its full definition or explain exclusions. The brief summary states 98 randomized patients, whereas the enrollment field reports 96. The discrepancy is not explained. This means the analysis population should be kept distinct from both general study enrollment and the randomized count in the brief summary.

In general, a comparison based on an analysis subset can differ from one based on all randomized participants if membership depends on post-randomization events or missing outcomes. The record does not provide enough information to determine whether such selection could affect this result. The statistical plan, missing-data procedure, and sensitivity analyses are not reported in the registry record.

What can be concluded from the reported precision?

The estimate is -0.77 points and the interval extends from -8.84 to 7.30. These values describe the precision of the reported contrast in the context of its model. The interval includes no difference but also leaves uncertainty about effects on either side. It should not be reduced to the claim that the observed groups were identical. Nor does the estimate alone show whether a difference would matter to patients, because the record provides no minimal important difference or other interpretation threshold.

The registry has multiple outcomes and analyses, including 12 outcome measures and 21 analyses. In general, testing many outcomes or comparisons can raise the chance of at least one apparently notable result if no adjustment or prespecified hierarchy is used. The record does not report the multiplicity strategy, the status of each analysis as prespecified or exploratory, or the handling of repeated assessments. As a result, the p-value should be interpreted as reported for this primary comparison, without assuming a particular family-wise or false-discovery adjustment.

Planning calculations based on an observed effect, where shown, are illustrations under stated assumptions rather than observed power. In general, post hoc power calculations based on the observed estimate do not add independent evidence to the confidence interval and p-value. The record does not state that such an illustration was part of the trial’s original design, and the original sample-size justification is not reported.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a least-squares mean difference in final WORC values of -0.77, with a 90% confidence interval from -8.84 to 7.30 and p = 0.875. This is the sponsor-reported analysis result for the Week 14 endpoint. The registry record does not identify a discrepancy between the posted sponsor result and any recalculation, so the sponsor’s own analysis remains the reported basis for interpretation.

The difference is a model-based contrast, whereas the arm summaries are presented separately as values of 37.0 for secukinumab and 37.77 for placebo. A simple subtraction of those arm summaries would not necessarily reproduce a least-squares mean difference, because model-based estimates can depend on covariates, baseline values, and analysis choices. The registry record does not give sufficient model detail to reconstruct the reported contrast from the group summaries.

The interval includes zero, and the p-value is 0.875. These results indicate that the reported superiority analysis does not provide strong evidence of a difference at Week 14. They do not establish equivalence, and they do not eliminate uncertainty about the possible size or direction of the contrast. No separate recalculation should supersede the sponsor’s stated analysis for this endpoint.

11. Multiplicity, Missing Data and Analysis Populations

The record lists 12 outcome measures and 21 analyses. The primary endpoint is the total WORC score at Week 14, and 11 secondary outcomes are posted. The available information also identifies repeated assessments over time for several outcomes. Multiple outcomes, time points, and analyses can create multiple opportunities to observe a result that appears noteworthy by chance. This is a general statistical concern; the registry does not report how it addressed that concern.

A prespecified testing hierarchy or multiplicity adjustment can define how evidence is evaluated across multiple hypotheses. Neither a hierarchy nor a correction method is reported in the registry record. It is also not reported which analyses were prespecified, how the primary endpoint was protected from other testing, or whether any interim analyses were performed. The absence of those details does not establish that no such procedures existed; it means they cannot be assessed from this record.

The primary outcome is described for the Pharmacodynamic Analysis Set. The registry does not provide the set’s detailed definition, a participant flow account, or the number and reasons for missing Week 14 measurements. Missing-data methods, assumptions about missing outcomes, and sensitivity analyses are not reported in the registry record. These omissions matter because complete-case or model-based results can depend on how missing observations arise and how they are handled.

The listed enrollment is 96, while the brief summary says 98 patients were randomized. The registry does not explain the difference. The endpoint counts, 47 for secukinumab and 41 for placebo, are from the named PD Analysis Set; they should not be interpreted as an explanation of the enrollment discrepancy. Without participant disposition and analysis-set definitions, the relationship among these counts cannot be established.

The record also does not provide the statistical analysis plan, the original sample-size justification, or a detailed account of model assumptions. These gaps restrict evaluation of prespecification, missing-data robustness, and the role of the multiple reported analyses. The primary result can still be described as posted, but its full analytic context is not available in the registry record.

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 2% reporting threshold.

Most frequent non-serious adverse event terms

For serious adverse events, the registry reports zero events judged related to treatment in the AIN457 300 mg s.c. group, among 49 participants at risk, and zero in the placebo group, among 47 participants at risk. It also reports zero deaths in each group. These are the serious-event and death figures available in the record; they do not summarize every possible safety outcome.

The registry separately reports other adverse events in 36 participants in the AIN457 group, among 49 at risk, and 34 participants in the placebo group, among 47 at risk. Those figures are not serious adverse event counts. The record does not provide the event terms or severity details for these other adverse events in the registry record. No top serious-event terms are listed.

Zero treatment-related serious events in the posted data should not be interpreted as proof that serious events cannot occur or that the groups have identical safety. Safety observations depend on the participants observed, the duration and completeness of follow-up, and how events are collected and attributed. The record does not provide enough detail to assess those features or to infer comparative risk beyond the reported counts. These figures describe what was recorded in the registry, not a guarantee about an individual’s safety.

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

The central result is a Week 14 comparison of total WORC scores in the PD Analysis Set. The reported least-squares mean difference is -0.77 points, with a 90% confidence interval from -8.84 to 7.30 and p = 0.875. The interval includes zero, and the point estimate is close to zero on a scale running from 0, worst, to 100, best. These features describe the estimate and its uncertainty at this endpoint.

The result does not demonstrate that secukinumab and placebo are equivalent. Equivalence requires an appropriate design, a prespecified margin, and an analysis showing that the uncertainty lies within that margin. The registry record does not report an equivalence margin or an equivalence analysis. Likewise, a high p-value does not prove the absence of a treatment effect; it indicates that this comparison does not provide strong evidence against its null hypothesis under the reported method.

The result also does not establish that a particular score difference would or would not matter to patients. No clinical importance threshold is reported. The confidence interval allows a range of possible contrasts, and the record does not provide enough context to assign clinical labels to its limits. The outcome is specific to rotator-cuff patient-reported status at Week 14 and should not be generalized automatically to other outcomes, times, populations, or conditions.

The posted findings do not resolve the difference between the enrollment field’s 96 and the brief summary’s 98 randomized patients. The primary endpoint counts are for a PD Analysis Set, and its full definition and participant flow are not reported. Missing-data procedures and multiplicity handling are also not reported. Those limitations affect how fully the result can be evaluated but do not alter the numerical result reported by the sponsor.

The registry reports no treatment-related serious adverse events and no deaths in either group, alongside other adverse event counts. Those safety figures are descriptive and should not be treated as proof of equal safety or absence of risk. Taken together, the record supports a narrow statistical description of the primary comparison and reported safety counts, not medical advice or a broad claim about treatment benefit.

14. Why This Trial Matters Statistically

This trial is statistically informative because it reports a direct randomized comparison of a patient-reported, condition-specific outcome between secukinumab and placebo. The primary contrast is presented with a confidence interval as well as a p-value. Reading both helps distinguish the estimated direction from the uncertainty around its size: the point estimate is -0.77, while the 90% confidence interval runs from -8.84 to 7.30 and includes zero.

The result also illustrates why a non-significant superiority test is not the same as evidence of equivalence. The p-value is 0.875, but the interval does not collapse to zero; it spans possible contrasts on both sides. Without an equivalence margin and a design intended to assess equivalence, a reader should not translate this result into a claim that the treatments have the same effect. This distinction is a general lesson in interpreting clinical comparisons.

The endpoint’s patient-reported nature adds a useful perspective to the study question. WORC covers physical symptoms, sport and recreation, work, lifestyle, and emotional function. At the same time, an endpoint’s relevance does not replace the need for a clearly described analysis population, missing-data methods, and an interpretation threshold. Those details are not reported in the registry record.

The record also shows why trial summaries need careful reconciliation. Enrollment is listed as 96, while the brief summary states that 98 patients were randomized. The primary analysis is in the PD Analysis Set and includes group counts of 47 and 41. These are distinct reported figures, and the record does not explain how they relate. Keeping the populations separate prevents unsupported totals or assumptions about participant flow.

Finally, the study has multiple outcomes and analyses, but the record does not describe a multiplicity strategy or detailed analysis plan. The primary result can be read as reported, while the broader evidence across outcomes remains harder to assess. This is a useful reminder that transparent reporting of analysis populations, missing data, and multiplicity is part of interpreting a clinical trial—not an optional detail after the effect estimate.

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.

The primary comparison is reported for the Pharmacodynamic Analysis Set, but the registry record does not give the set’s operational definition or a complete participant flow. It is therefore unclear from this record why the endpoint counts differ from the brief summary’s randomized figure. The enrollment field also reports a different figure from the brief summary, and no explanation is given. These inconsistencies constrain assessment of who contributed to the analysis.

The registry does not report the model specification behind the least-squares mean difference, including any covariate adjustment or baseline handling. It also does not provide missing-data methods, the amount or pattern of missing Week 14 data, or sensitivity analyses. Consequently, the robustness of the reported estimate to alternative assumptions cannot be assessed from the registry information described.

The study includes multiple outcomes and analyses, but no multiplicity approach, testing hierarchy, or detailed prespecification information is reported. The original sample-size justification and statistical analysis plan are also not reported in the registry record. This limits evaluation of whether the primary testing procedure and broader outcome interpretation followed a prespecified strategy. Any planning illustration based on the observed effect is not a substitute for the original design justification or evidence of observed power.

The primary endpoint is measured at Week 14, while the official title describes a 24-week study and the arm descriptions specify 12 weeks of treatment. The record does not explain the timing and purpose of the remaining study period. It also uses both double-blind and quadruple masking labels without identifying the masked roles. These details do not change the posted primary estimate but limit the description of trial conduct available from the registry.

Finally, no clinical importance threshold is reported for the WORC score, and the serious-event figures alone cannot characterize the full safety profile. The primary confidence interval and p-value quantify uncertainty under the reported analysis, but they do not resolve these design, reporting, and interpretation limitations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Efficacy, Safety and Tolerability of AIN457 in Patients With Active Overuse Tendinopathy — NCT03344640.
• Registry record last updated 2021-10-08; status last verified 2021-10.
• Results first posted 2020-12-09.
• 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

NCT03344640 is a completed randomized, parallel-group Phase II study of subcutaneous secukinumab 300 mg versus placebo for active overuse rotator-cuff tendinopathy. The treatment descriptions specify 12 weeks. The primary outcome is total WORC score at Week 14 (Day 99), measured in the Pharmacodynamic Analysis Set.

The sponsor-reported least-squares mean difference in final values is -0.77, with a 90% confidence interval from -8.84 to 7.30 and p = 0.875. The interval includes zero, and the result does not establish equivalence. Serious adverse events judged related to treatment and deaths are reported as zero in both groups.

The registry lists enrollment of 96, while the brief summary says 98 patients were randomized. The reason for the discrepancy, detailed participant flow, missing-data methods, multiplicity strategy, and full statistical plan are not reported in the registry record.