A Proof-of-concept Study to Evaluate the Efficacy and Safety of Rozanolixizumab to Treat Adult Study Participants With Severe Fibromyalgia Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Proof-of-concept Study to Evaluate the Efficacy and Safety of Rozanolixizumab to Treat Adult Study Participants With Severe Fibromyalgia Syndrome (NCT05643794), a randomized phase 2 study. The primary outcome is Brief Pain Inventory Short Form (BPI-SF) Average Interference Score at 12 Weeks of Treatment.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, placebo-controlled, multicenter phase 2A proof-of-concept study of rozanolixizumab in adults with severe fibromyalgia syndrome. Its model is listed as crossover, meaning treatment comparisons are made in a study structure that includes participants receiving treatment at different times or in different sequences. The record identifies quadruple masking, but does not specify which groups of people were masked or how masking was maintained.

The study lists three treatment sequences. Participants in Treatment sequence 1 received rozanolixizumab and placebo during the dosing period at prespecified timepoints. The same general description is given for Treatment sequence 2. Participants in Treatment sequence 3 received placebo during the dosing period at prespecified timepoints. More detailed sequence schedules, treatment durations for each period, washout arrangements, and the allocation ratio are not reported in the registry record. They should not be inferred from the sequence labels alone.

Enrollment was 63. The registry lists the study as completed, with a start date of 2022-12-21 and a primary completion date of 2024-05-28. These are record-level study dates, not an account of when individual participants entered or completed treatment. The enrollment figure also does not mean that all enrolled participants contributed to every outcome analysis. For the primary endpoint, the stated Full Analysis Set required treatment exposure, a baseline value, and at least one post-baseline efficacy assessment. The analysis population size is not separately described beyond the arm-level counts reported for the endpoint.

The design details that would clarify how crossover periods, sequence effects, or missing observations were handled are not reported in the registry record. The registry also does not report a sample-size justification or a detailed protocol synopsis. Those omissions limit how fully the design and its analysis can be reconstructed 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: The Participant Flow refers to the Randomized Set.

Run-In (2 Weeks)

Treatment Period 1 (12 Weeks)

Reasons for not completing this period:

Treatment Period 2 (12 Weeks)

Reasons for not completing this period:

Run-Out Period (2 Weeks)

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) included all study participants who received any study treatment, including during the run-in period, had a baseline value and at least one post-baseline efficacy endpoint assessment.

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 Randomized Set (RS) included all enrolled participants who were randomized into the study.

6. Primary Endpoint

The registry lists the primary outcome as Brief Pain Inventory Short Form (BPI-SF) Average Interference Score at 12 Weeks of Treatment, measured over At 12 weeks of treatment.

The primary endpoint was the Brief Pain Inventory Short Form Average Interference Score at 12 weeks of treatment. The BPI-SF is a self-administered questionnaire that assesses pain severity and the impact of pain on daily functioning. Its interference items cover general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each item is rated from 0, meaning did not interfere, to 10, meaning completely interfere, with a 24-hour recall period.

The registry describes the overall interference score as ranging from 0-70, with higher scores indicating greater interference. This endpoint is used to represent the effect of pain on everyday functioning, rather than pain intensity alone. That distinction matters: a change in interference captures reported impact across several areas of life. It remains a questionnaire-based outcome, so interpretation depends on the participant reports and the scoring procedure.

The primary result compares the least-squares mean score for RLZ at 12 weeks with the placebo score. The endpoint description identifies the Full Analysis Set as participants who received any study treatment, including during run-in, had a baseline value, and had at least one post-baseline efficacy endpoint assessment. Further details about handling missing item responses or incomplete questionnaires are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: each participant contributes a score rather than a count of events. The registry identifies the reported arm summaries as least-squares means and gives 95% confidence intervals for each. A least-squares mean is a model-based mean estimate. In general, model-based means can account for features of the design specified in the model, whereas a simple average summarizes observed scores without that adjustment. The exact adjustments used for these least-squares means are not reported in the registry record.

The primary analysis method is described as a longitudinal linear mixed effect model. In general, a longitudinal model is suited to repeated observations over time, and a mixed-effects model can represent dependence among observations from the same participant. This can be relevant in a crossover study, where participants may contribute information during more than one treatment period. The model description alone does not reveal which time effects, sequence effects, participant-level terms, or other covariates were included. Those details are not reported in the registry record, so the model cannot be independently reconstructed from the method name alone.

The reported contrast is Difference from Placebo. It is -0.54, with a 95% confidence interval from -1.24 to 0.16. For a treatment contrast, 0 represents no difference on the modeled score scale. In general, a confidence interval conveys both the direction and precision of an estimate: a narrower interval indicates less uncertainty under the model, while a wider interval indicates more. This interval extends across 0, leaving uncertainty about whether the underlying contrast is below, at, or above no difference. The interval is not a guarantee that the true value lies within its endpoints.

The p-value for the reported contrast is 0.129. In general, a p-value describes how compatible the observed data are with a specified null model, conditional on the analysis assumptions; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. The registry does not report the prespecified alpha level for this primary analysis, the exact hypothesis-testing procedure, or whether the p-value is adjusted for other analyses. The assumptions listed for planning illustrations are not evidence of the trial's own testing plan.

The primary endpoint description gives the Full Analysis Set definition. Participants had to receive any study treatment, including during run-in, have a baseline value, and have at least one post-baseline efficacy endpoint assessment. Such a definition clarifies who could contribute to this analysis, but it does not explain what happened to participants who lacked a later measurement, or how partial assessments were handled. Missing-data methods are not reported in the registry record.

General statistical context: crossover studies can be efficient because treatment observations may be obtained from the same participant under different conditions. They also require attention to treatment period, sequence, and possible effects that persist from one period into another. Those considerations are not a claim about problems in this study; they are features an analysis plan may need to address. The registry gives the crossover model label but does not report whether or how these issues were assessed.

The record lists 7 outcome measures and 6 posted secondary outcomes, as well as 5 analyses. It does not report a multiplicity adjustment or explain how the primary and secondary outcomes were ordered for confirmatory testing. When many outcomes or comparisons are examined, general statistical practice recognizes that the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiplicity. Whether such a concern was addressed in the trial is not reported in the registry record.

Planning illustrations based on an observed effect are not observed power and are not the trial's sample-size justification. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For continuous outcomes, those illustrations are expressed as participants per arm for 80% power or participants per arm for 90% power. The registry's own sample-size rationale and the details needed to treat those illustrations as a design plan are not reported in the registry record.

10. Analyses Reported by the Sponsor

The registry reports the primary comparison using a longitudinal linear mixed effect model. Its reported estimate is a difference from placebo of -0.54, with a 95% confidence interval from -1.24 to 0.16 and a p-value of 0.129. The arm-level least-squares means are 5.76 for RLZ and 6.3 for placebo. These are the sponsor's reported model-based results in the registry record.

A separate simple, unadjusted re-calculation of the primary contrast is not reported in the registry record. The posted arm summaries are least-squares means, and the study is described as a crossover with a longitudinal mixed model; a direct subtraction of arm summaries would not necessarily reproduce the model-based treatment contrast. The model specification needed to explain any such difference is not reported.

The record does not flag a discrepancy between a sponsor analysis and a recalculation. The sponsor's model-based estimate and interval therefore remain the relevant reported inferential result. They should not be replaced with an unadjusted contrast that is not reported, nor treated as if the posted arm means alone reveal the underlying model. The confidence interval includes 0, conveying uncertainty around the reported treatment difference.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including the primary endpoint, and 6 posted secondary outcomes. The secondary outcomes include treatment-emergent adverse events, withdrawals due to those events, and several patient-reported measures: BPI-SF Average Interference Score at 24 weeks, Revised Fibromyalgia Impact Questionnaire score at 12 weeks, average daily pain score at 12 weeks, and fatigue score at 12 weeks. The record also lists 5 analyses. It does not explain how those analyses map to all outcomes or comparisons.

Multiplicity arises when several outcomes, time points, or contrasts are tested. In general, examining multiple statistical tests without an adjustment or prespecified hierarchy can increase the chance of at least one result appearing notable by chance. An adjustment or testing hierarchy can address that issue, but may also affect the interpretation and precision of individual tests. The registry does not report whether the primary result was protected from other testing, whether secondary outcomes were confirmatory or exploratory, or whether any multiplicity procedure was used. A definitive account of the testing family is therefore not possible from the registry record.

The primary analysis population is described as the Full Analysis Set: participants who received any study treatment, including during the run-in period, had a baseline value, and had at least one post-baseline efficacy endpoint assessment. This definition does not establish how many participants lacked an endpoint value or how missing assessments were handled. The registry does not report imputation, a missing-data model, sensitivity analyses, or reasons for missing data. Such choices can matter for a longitudinal analysis because the estimate may depend on what is assumed about observations that are absent.

The registry also does not report the protocol's statistical analysis plan, including any prespecified handling of crossover periods, sequence effects, or incomplete treatment periods. These omissions do not prove that the issues were not considered; they mean the approach is not reported in the registry record. Consequently, the primary estimate can be described as posted, but the full analysis strategy and its safeguards against missing-data or multiplicity concerns cannot be independently assessed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (5.0%), headache (4.8%), back pain (4.8%), respiratory syncytial virus bronchiolitis (2.4%), intervertebral disc protrusion (2.4%).

The registry reports serious adverse event counts by treatment period or sequence group, rather than as one undifferentiated comparison. The counts were 0 among 63 participants in Run-In-PBO, 0 among 22 in TP1-RLZ, and 3 among 41 in TP1-PBO. For the listed TP2 groups, there were 0 among 18 in TP2-RLZ/RLZ, 0 among 19 in TP2-PBO/RLZ, and 0 among 20 in TP2-PBO/PBO. During Run-Out and SFU, the counts were 0 among 22 in RLZ/RLZ, 1 among 20 in PBO/RLZ, and 2 among 21 in PBO/PBO. Deaths are reported as 0 in each listed group.

These are counts within groups with different numbers at risk and at different parts of the crossover study. Participants may contribute to more than one period or group, so adding group counts or comparing them as if they were independent parallel arms would require information not reported in the registry record. The listed serious adverse event terms include pulmonary embolism at 5.0%, headache at 4.8%, back pain at 4.8%, respiratory syncytial virus bronchiolitis at 2.4%, intervertebral disc protrusion at 2.4%, and neck pain at 2.4%. The registry record does not provide enough context in these figures alone to attribute events to treatment or establish comparative risk.

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

The primary result is an estimate of the difference in BPI-SF interference score at 12 weeks, not a complete summary of every outcome in the study. RLZ had a reported least-squares mean score of 5.76 and placebo had a reported least-squares mean score of 6.3. The model-estimated difference from placebo was -0.54. Because higher BPI-SF interference scores indicate greater interference, the negative estimate is in the direction of a lower score for RLZ in this analysis.

The 95% confidence interval from -1.24 to 0.16 includes 0. This means the results leave uncertainty about the direction and size of the underlying difference under the analysis model. The p-value of 0.129 is another summary of the comparison, but neither it nor the point estimate answers whether the observed difference would be important to participants. A threshold for a clinically important BPI-SF difference is not reported in the registry record.

The result does not establish that rozanolixizumab improves or worsens fibromyalgia, and it should not be used as treatment advice. It describes the posted analysis for a particular outcome, time point, and analysis population in this study. It also does not show what would happen with another dosing schedule, in another population, or over a different period of observation.

The study's crossover design and reported model matter. The posted estimate comes from a longitudinal linear mixed effect model; it is not simply a comparison of two independent group averages. However, the registry does not report enough detail about the model terms, missing data, or sequence handling to independently assess those choices. The record's definition of the Full Analysis Set is useful, but it does not supply the number of participants excluded from the endpoint analysis or explain their outcomes.

Finally, the primary endpoint is one of several outcomes listed in the record. The primary result should not be generalized to the secondary measures, including pain, fatigue, function, or adverse events. The registry does not report a multiplicity plan or a clinical-importance threshold. The most grounded interpretation is therefore limited: the reported model estimated a lower RLZ interference score than placebo, while the confidence interval includes no difference and leaves meaningful uncertainty about the size and direction of the effect.

14. Why This Trial Matters Statistically

This study is statistically notable for its crossover structure and repeated-measures analysis. In a crossover design, the same participant can provide observations under different treatment conditions, potentially allowing a comparison that accounts for within-participant information. That feature also makes the analysis dependent on how treatment periods, sequences, and repeated measurements are represented. The registry identifies a longitudinal linear mixed effect model but does not report enough specification to assess those details.

The primary result also illustrates why a point estimate should be read together with its interval. The reported difference of -0.54 is the single best estimate from the model, but the 95% confidence interval from -1.24 to 0.16 includes 0. The interval communicates uncertainty that is not captured by the point estimate alone. The p-value of 0.129 adds another inferential summary, but neither statistic substitutes for a prespecified analysis plan or a threshold for clinical importance.

The registry defines the Full Analysis Set and reports enrollment of 63, while the endpoint summaries show 41.0 in each displayed arm. These figures serve different purposes: enrollment describes the study record, whereas analysis counts relate to the reported endpoint summaries. The record does not explain the relationship between those counts in detail, underscoring why an analysis population should not be inferred from enrollment alone.

More broadly, the study gives an example of the distinction between a posted model-based result and what can be independently reconstructed from summary statistics. With a crossover design, least-squares means, and limited model detail, the reported treatment contrast is the most direct inferential result available. Missing information about multiplicity, missing data, and the sample-size rationale also defines the limits of what can be concluded statistically from the registry record.

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 registry provides the primary endpoint definition, analysis population criteria, arm summaries, and a method label, but not a full statistical analysis plan. Specific model terms, treatment-period handling, sequence effects, and the approach to possible carryover are not reported in the registry record. These details are relevant to evaluating a crossover analysis and cannot be reconstructed from the method name alone.

The endpoint analysis population is defined, but the number of participants contributing to each treatment period and the relationship between the Full Analysis Set and the arm-level counts are not explained in detail. The registry does not report the extent or reasons for missing endpoint data, how incomplete questionnaire items were scored, or how missing observations were handled. It also does not report sensitivity analyses that could show whether the estimate changes under alternative missing-data assumptions.

The record lists multiple outcomes and analyses but does not report a multiplicity strategy or a testing hierarchy. It does not state whether secondary outcomes were exploratory or confirmatory. A sample-size justification for the trial is not reported in the registry record; planning illustrations based on an observed effect are not a substitute for the original design rationale.

The primary endpoint is a self-administered interference score with a 24-hour recall period. The registry describes its scale and interpretation, but does not report a threshold for a clinically important difference. Thus, statistical precision can be described from the interval, while clinical importance cannot be determined from a prespecified threshold in the record.

The safety summaries are divided across study periods and sequence groups, with differing numbers at risk. The record does not provide enough information in those counts alone to make a comparative safety estimate or attribute events to a treatment. These limitations restrict interpretation of the registry-level evidence; they do not establish that the omitted analyses were not conducted elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Proof-of-concept Study to Evaluate the Efficacy and Safety of Rozanolixizumab to Treat Adult Study Participants With Severe Fibromyalgia Syndrome — NCT05643794.
• Registry record last updated 2025-07-01; status last verified 2025-06.
• Results first posted 2025-07-01.
• 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

NCT05643794 is a completed, randomized, double-blind, placebo-controlled, multicenter phase 2A proof-of-concept crossover study of rozanolixizumab in adults with severe fibromyalgia syndrome. Registry enrollment was 63. The primary endpoint was the BPI-SF Average Interference Score at 12 weeks of treatment, analyzed in the Full Analysis Set described in the record.

The registry reports least-squares mean scores of 5.76 for RLZ and 6.3 for placebo. The model-estimated difference from placebo was -0.54, with a 95% confidence interval from -1.24 to 0.16 and a p-value of 0.129. Higher BPI-SF scores indicate greater interference, and the interval includes 0. The record also reports secondary outcomes and adverse event summaries, but does not report a full statistical analysis plan, multiplicity procedure, missing-data approach, or sample-size justification.