A Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Rozanolixizumab in Study Participants With Persistent or Chronic Primary Immune Thrombocytopenia (ITP): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Rozanolixizumab in Study Participants With Persistent or Chronic Primary Immune Thrombocytopenia (ITP) (NCT04596995), a na phase 3 study. The primary outcome is Percentage of Participants With Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This is a Phase 3, open-label extension study of rozanolixizumab in participants with persistent or chronic primary ITP. The registry lists a single-group model, allocation as NA, and masking as none. These design features mean that the study does not include a randomized, masked control arm for comparison. The registry reports enrollment of 43 participants.

The treatment description states that participants received fixed-unit doses of rozanolixizumab across body-weight tiers at prespecified time points during the Treatment Period. Doses could be adjusted based on platelet count values or medical needs. The record does not give more detail about the dosing schedule or the rules used for dose adjustment.

The recorded study start was 2021-01-06, and primary completion was 2022-12-21. The study status is terminated. The reason for termination is not reported in the registry record, so the status alone does not explain whether the study ended as planned or why it stopped.

The primary outcome concerns the percentage of participants with TEAEs, measured from baseline through the end of the Safety Follow-Up Period, up to Week 60. The registry defines the Safety Set as participants who received at least 1 dose of study treatment. Listed secondary outcomes concern a stable clinically meaningful response without rescue therapy at at least 70% of visits over the planned 52-week Treatment Period starting at Week 4, and change in the ITP-PAQ Symptoms Domain Score to Week 53 or 55.

Because this is an extension study without a like-for-like control group, its design is suited to describing outcomes among treated participants, not estimating a randomized treatment contrast. The registry record does not report the protocol rationale, detailed eligibility criteria, or a sample-size justification.

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: Participant Flow refers to the Enrolled Set.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Set included all study participants who received at least 1 dose of IMP (partial or full).

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: Baseline Characteristics refer to Enrolled Set which consisted of all study participants who signed the informed consent form (ICF).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), measured over From Baseline to end of Safety Follow-Up Period (up to Week 60).

The primary endpoint is the percentage of participants with treatment-emergent adverse events (TEAEs), assessed from baseline to the end of the Safety Follow-Up Period, up to Week 60. The registry defines an adverse event as an untoward medical occurrence temporally associated with use of the investigational medicinal product, whether or not it is considered related to that product. TEAEs are events starting after the first administration and up to and including 8 weeks (56 days) after the final dose.

In general, a participant-level percentage gives the proportion of the defined analysis population who experienced at least one event meeting the endpoint definition. This is useful for describing how often such events were reported during the specified observation period. It does not, by itself, establish that treatment caused an event: the definition is based on timing and includes events not considered related to treatment. Nor does a percentage alone describe the event’s duration, severity, or consequences.

The registry identifies the Safety Set as all participants who received at least 1 dose, partial or full. However, the primary endpoint’s numerical result is not reported in the registry record. The adverse-event summary includes other safety figures, but those do not substitute for a reported result for the specified primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts with the question an endpoint is designed to answer and the population in which it is measured. Here, the primary endpoint is a participant percentage for TEAEs, and the stated Safety Set includes anyone who received at least 1 dose, partial or full. In general, a participant-level percentage classifies each participant according to whether they experienced one or more events meeting the endpoint definition during the specified period. It is not the same as a count of all event episodes: one participant may have more than one event, while the participant-level measure records whether the event criterion was met.

The registry describes the time window and event definition. Events must begin after the first dose and can qualify through 8 weeks (56 days) after the final dose. This timing rule defines which events count as treatment-emergent; it does not prove that the investigational product caused them. The registry’s definition explicitly includes events whether or not they are considered related to the product. In general, temporal association is a useful safety-monitoring convention, but causal attribution requires more than observing that an event occurred during or after treatment.

What does a confidence interval add?

In general, a confidence interval communicates the uncertainty around an estimated quantity, such as a participant percentage. A narrower interval indicates greater statistical precision under the assumptions of the analysis; a wider interval indicates more uncertainty. A point estimate alone does not show that uncertainty. The primary endpoint’s numerical estimate and confidence interval are not reported in the registry record, so neither its magnitude nor its precision can be evaluated from this record.

The single-group design also shapes what analyses can support. A descriptive percentage can characterize the observed group, but the study has no concurrent comparator in the registry design. An estimate of the difference between treatment and control groups is therefore not available from this design. General statistical methods cannot create a randomized comparison where none was assigned. Comparisons with external data would require information and assumptions not reported in the registry record.

How should the sample-size illustrations be understood?

In general, sample-size calculations are planning tools that describe how many participants per arm might be needed under specified assumptions about the effect, significance level, allocation, and statistical approximation. The planning description associated with these calculations specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of the observed effect. These are planning assumptions, not a description of the trial’s single-group design.

Such illustrations are not evidence that a study had a particular probability of detecting an effect after it was completed. They are not observed power. They also do not establish the study’s original design rationale or sample-size justification; that justification is not reported in the registry record. A two-arm planning scenario should not be confused with the actual single-group extension study. The registry record does not report a sample-size calculation as part of the trial’s design rationale.

In general, a normal approximation represents a distribution using a normal curve to simplify estimation or testing. Its suitability depends on the quantity being modeled and the available data. For participant percentages, the underlying observations are binary at the participant level: each person either meets the event definition or does not. The registry record does not identify the method used for an analysis of the primary endpoint, and no primary analysis is reported.

What can the adverse-event counts establish?

The adverse-event summary provides participant counts, denominators, selected serious-event terms, and a death count. Such summaries can describe the reported events in the study group. They do not show whether the events were more or less common than they would have been in a control group, because the design has no concurrent comparator. They also do not establish whether a particular event was judged related to treatment. The listed percentages are reproduced as registry figures and should not be treated as comparative risks.

In general, interpretation of an event percentage also depends on the population included in its denominator and the observation time available for each participant. The record gives 43 at risk for the serious and other adverse-event categories, but does not report participant-level follow-up duration or missing-data handling for these summaries. The primary endpoint period is described as lasting through the end of Safety Follow-Up, up to Week 60; that maximum timeframe does not mean that every participant had identical observation.

Over-dispersion is a general concern when outcomes vary more than a model assumes, particularly for clustered or count data. The primary endpoint is specified as a participant percentage, and the registry does not report a model or distributional assumption for its analysis. There is therefore no basis in the record to claim that over-dispersion was assessed or to say how it affected an estimate. More broadly, statistical methods should be matched to the outcome and study design, but the specific analysis methods used for the listed outcomes are not reported in the registry record.

No recalculated unadjusted estimate is presented for the primary endpoint, because the registry record does not provide its numerical result. The posted serious-event terms and counts are descriptive registry entries, not a substitute for an inferential analysis. Any interpretation should distinguish those observed summaries from an estimated treatment effect, which this single-group record does not provide.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Rozanolixizumab")
n      <- c(43)
events <- c(39)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Rozanolixizumab  43  39  90.7  77.9  97.4  78.4  96.3  78.3  96.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety endpoint and secondary outcomes concerning response without rescue therapy and a patient-reported Symptoms Domain Score. It does not report a multiplicity plan in the registry record. In general, multiplicity arises when several outcomes or statistical tests are examined: without an appropriate plan, the chance of at least one apparently notable result can increase. The record does not state whether or how any adjustment was planned, and no inferential analyses are reported.

Missing-data methods are not reported in the registry record. The record defines the Safety Set as participants who received at least 1 dose, partial or full, but it does not describe how missing endpoint observations, incomplete follow-up, or participant withdrawals were handled. The enrollment count alone does not establish the number analyzed for every outcome. The duration and completeness of each participant’s observation are also not reported.

The registry record does not report interim analyses, a detailed statistical analysis plan, or the methods used to analyze the primary or secondary outcomes. These details should not be inferred from the endpoint descriptions or from the presence of adverse-event summaries. Because the study is single group, the listed outcomes also do not yield a randomized comparison. The reason for termination is not reported in the registry record, so its relationship, if any, to follow-up completeness or analysis decisions cannot be 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: covid-19 (4.7%), uterine haemorrhage (4.7%), immune thrombocytopenia (2.3%), pyrexia (2.3%), joint dislocation (2.3%).

The safety summary reports 9 participants affected in the serious adverse-event category among 43 at risk, 31 affected in the other adverse-event category among 43 at risk, and 0 deaths. It also lists six serious adverse-event terms with registry percentages: COVID-19 and uterine haemorrhage at 4.7% each, and immune thrombocytopenia, pyrexia, joint dislocation, and radius fracture at 2.3% each. These are registry summaries, not comparisons against another group.

In general, an adverse-event term indicates an event recorded under that description; it does not by itself demonstrate that treatment caused the event. The registry’s TEAE definition includes events based on their timing and whether or not they were considered related to the investigational product. The listed serious-event terms should therefore be read as reported events during the study, not as causal conclusions.

The summary does not provide detail about the duration, clinical course, or relatedness of each event. It also does not give a concurrent control rate. The counts describe participants in the treated group and cannot establish how often these events would have occurred in a comparable group without rozanolixizumab.

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

The registry record describes a Phase 3, open-label extension study in which 43 participants were enrolled and received rozanolixizumab in a single group. Its primary endpoint was the percentage of participants with TEAEs during the period from baseline to the end of Safety Follow-Up, up to Week 60. The record gives the endpoint definition but does not report its numerical result. This means the primary safety outcome cannot be quantified or assessed for statistical precision from the registry record.

The posted adverse-event summary gives counts for participants in serious and other adverse-event categories, reports 0 deaths, and lists selected serious-event terms and percentages. Those figures are descriptive. With no concurrent control group, they do not estimate a treatment-versus-control difference, and they cannot establish that treatment caused any listed event. The registry definition of TEAEs includes events whether or not considered related to the investigational product.

The record also identifies secondary outcomes about response without rescue therapy and change in the ITP-PAQ Symptoms Domain Score. Their numerical results are not reported in the registry record. It is not possible to infer those results from the study’s title, treatment description, enrollment, or safety summary.

In general, an extension study can provide observations about participants who continue into a longer period of follow-up, but interpretation depends on who enters, who remains under observation, and how outcomes are analyzed. Details of eligibility, missing data, and outcome-specific analysis populations are not reported in the registry record. The termination status is recorded, but its reason is not reported. Thus, the available information supports a careful description of the study design and selected safety summaries, not a definitive assessment of comparative safety or efficacy.

The distinction between an endpoint being named and an endpoint result being reported is important. A defined endpoint establishes what investigators intended to measure; it does not reveal the observed estimate. Likewise, a count of adverse events is not an estimate of treatment effect. Conclusions about differences, causes, and precision require results and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates an important statistical distinction between documenting an outcome and reporting an estimate for that outcome. The registry specifies TEAEs as the primary endpoint, including the analysis population and observation window, but does not report the percentage observed. Without that estimate, the primary endpoint cannot be described quantitatively or assessed for precision. Clear endpoint definitions are valuable, but they do not replace outcome results.

The single-group, open-label extension design also makes the scope of inference especially important. The adverse-event figures can describe what was recorded among treated participants, but the absence of a concurrent comparator prevents a direct randomized comparison. This is a general design limitation, not a statistical defect that can be resolved by calculating a different summary from the same group.

The record further demonstrates why adverse-event counts, event terms, and treatment causality should be kept separate. The registry defines TEAEs by timing and includes events regardless of whether they were considered related to treatment. A listed event is therefore a safety observation, not proof of a causal relationship. Similarly, a zero count for deaths in the summary does not provide a comparative estimate.

Finally, the record lists secondary efficacy-related outcomes while not reporting their numerical results or analysis methods. This highlights the value of transparent reporting for outcome estimates, uncertainty, missing-data handling, and multiplicity. When these details are absent, readers should limit conclusions to what the registry actually reports and avoid filling gaps with assumptions.

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 principal limitation for statistical interpretation is that the primary TEAE endpoint is described but its numerical result is not reported in the registry record. No estimate or confidence interval is reported, so the endpoint’s observed frequency and precision cannot be assessed. Numerical results for the listed secondary outcomes are also not reported.

The single-group design has no concurrent comparator, and the study is open label with masking listed as none. Therefore, the record does not support a randomized treatment contrast. Adverse-event summaries can be described for the enrolled group, but they cannot establish comparative event rates or causal effects. The event definition includes occurrences whether or not considered related to the investigational product.

The registry does not report the reason for termination, the number completing follow-up, outcome-specific analysis populations, missing-data methods, or the detailed statistical analysis plan. It also does not report a multiplicity approach, interim analyses, or the sample-size justification. These omissions limit assessment of how outcomes were selected, analyzed, and interpreted. The stated maximum safety follow-up timeframe does not establish that all participants were observed for the same duration.

Finally, the adverse-event summary is limited to the counts, death figure, and selected serious-event terms posted in the registry. It does not give further details about event duration, severity beyond the serious-event classification, or relatedness. The status of terminated does not explain whether these limitations arose from early stopping or another circumstance; the reason is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Rozanolixizumab in Study Participants With Persistent or Chronic Primary Immune Thrombocytopenia (ITP) — NCT04596995.
• Registry record last updated 2024-02-05; status last verified 2024-01.
• Results first posted 2024-02-05.
• 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

The registry record describes a Phase 3, open-label, single-group extension study of rozanolixizumab in participants with persistent or chronic primary ITP. It reports enrollment of 43, study status as terminated, a start date of 2021-01-06, and primary completion on 2022-12-21. The reason for termination is not reported in the registry record.

The primary endpoint is the percentage of participants with TEAEs through the end of Safety Follow-Up, up to Week 60. The registry defines the Safety Set as participants who received at least 1 dose. The primary endpoint result is not reported. The safety summary lists 9 participants in the serious adverse-event category, 31 in the other adverse-event category, and 0 deaths, along with selected serious-event terms and percentages. Secondary outcomes concern response without rescue therapy and change in the ITP-PAQ Symptoms Domain Score; their results are not reported in the registry record.