Basket Study to Assess Efficacy, Safety and PK of Iptacopan (LNP023) in Autoimmune Benign Hematological Disorders: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Basket Study to Assess Efficacy, Safety and PK of Iptacopan (LNP023) in Autoimmune Benign Hematological Disorders (NCT05086744), a na phase 2 study. The primary outcome is Cohort 1 (ITP): Number of Participants With a Clinically Meaningful Response.

2. Clinical Question

3. Trial Design

This was an open-label, multi-center, phase 2 basket study of iptacopan in autoimmune benign hematological disorders. The registry lists ITP and CAD as the conditions studied, with participants assigned to a single-group treatment model. Iptacopan was the only listed intervention, at 200 mg twice daily. There was no randomized comparator, and the registry lists allocation as not applicable. Consequently, outcomes in the two disease cohorts are not controlled treatment comparisons.

The study enrolled 19 participants. The registry record gives a start date of 2021-12-21, a primary completion date of 2023-09-20, and a status of terminated. It does not report why the study was terminated. The record also does not describe a control regimen or a masking procedure; masking is listed as none. These features matter for interpretation: participants and study personnel were not blinded, and changes over time cannot be separated from treatment effects using a concurrent control group.

The primary outcome applies to Cohort 1, the ITP cohort, and is framed as a count of participants meeting a response definition during up to 12 weeks of Part A. The registry identifies a pharmacodynamic analysis set and says results are presented overall and by sC5b-9 stratification group. It does not report the size or membership of those groups. CAD outcomes are listed among the secondary outcomes, including a hemoglobin threshold and rescue-therapy measures, but no outcome results are reported in the registry record.

The record lists 19 outcome measures and no analysis records. It does not report a detailed statistical analysis plan, a sample-size justification, or the reason for the study’s termination. The registry describes a study intended to evaluate efficacy and safety; the available record does not establish that the planned questions received a complete or reported analysis.

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 screening period began once patients had signed the study informed consent. Screening evaluations had to be completed within 8 weeks prior to the first dose of study treatment. The treatment period started on Day 1 of Part A.

Part A

Reasons for not completing this period:

Part B

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants from Cohort 1 in the Pharmacodynamic (PD) analysis set. Results are presented by sC5b-9 stratification group (sC5b-9 high and sC5b-9 low) and overall.

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.

6. Primary Endpoint

The registry lists the primary outcome as Cohort 1 (ITP): Number of Participants With a Clinically Meaningful Response, measured over Up to 12 weeks (Part A).

The primary endpoint counts participants in the ITP cohort who met a prespecified definition of clinically meaningful response during up to 12 weeks of Part A. A participant had to meet all three conditions: a platelet count of at least 50 k/μL sustained for at least 2 consecutive weeks during the main treatment part; no rescue therapy or prohibited medication to treat ITP; and no treatment discontinuation.

This is a binary participant-level endpoint: each participant either meets the complete response definition or does not. Combining a platelet-count threshold with requirements about rescue medication and treatment discontinuation makes the endpoint more demanding than a platelet measurement alone. It captures whether the specified count was sustained while also accounting for rescue treatment and discontinuation. It does not, by itself, describe the full pattern of platelet measurements, the duration of response beyond the stated threshold, or the reason a participant did not meet the definition.

In general, a binary endpoint can be easy to interpret as a response count, but it compresses variation in timing and magnitude into a responder/non-responder classification. The registry record reports the endpoint definition and analysis population, but does not report the number meeting the definition, a response estimate, or its uncertainty. No conclusion about the observed response can therefore be drawn from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the response count represent?

The primary measure is a count of participants who satisfy every part of the ITP responder definition. This type of endpoint is binary at the participant level: the endpoint is met or not met. The definition requires a sustained platelet-count threshold as well as no rescue therapy or prohibited ITP medication and no treatment discontinuation. A participant who does not satisfy any required component does not meet the complete definition. The registry record does not explain how borderline, missing, or incomplete component measurements were handled.

In general, a count is most interpretable alongside its denominator. The denominator should be the population actually included in the endpoint analysis, not automatically everyone enrolled. Here, the record identifies the pharmacodynamic analysis set as the primary endpoint population but does not report its size or the endpoint count. It also does not report a confidence interval. A confidence interval, as a general statistical concept, conveys the uncertainty around an estimate under the analysis assumptions; it does not replace the underlying study design or resolve biases from the absence of a control group.

What does the single-group design allow?

The study is listed as single-group, open-label, and without allocation to a randomized comparator. In general, a single-group study can describe what happened among participants receiving the study intervention. It cannot, on its own, show how outcomes would have differed under another treatment or no study treatment. Observed changes can reflect multiple influences, including the course of the condition and changes in care. Without a concurrent control group, those explanations are not separated by randomization.

Open-label status means masking was not used, as also indicated in the registry record. In general, knowledge of treatment assignment can influence participant reporting, clinical decisions, or outcome assessment, depending on the outcome and how it is measured. The primary endpoint includes a platelet threshold, but the complete responder definition also includes treatment-related decisions such as use of rescue therapy and discontinuation. The record does not describe safeguards or adjudication procedures for those components.

How should stratification be understood?

The registry says the ITP primary outcome was to be presented overall and by sC5b-9 high and low stratification group. Stratification can be used to describe outcomes across categories of a baseline or biological marker, or to organize an analysis. In general, subgroup results can be less precise than overall results when the subgroup sizes are limited. The record does not report the number in each sC5b-9 group, the subgroup estimates, or whether the stratification was used for any formal hypothesis test. These omissions prevent assessment of subgroup precision or interpretation of differences between strata.

What can significance tests and intervals tell readers?

In general, a significance test evaluates how compatible data are with a specified null hypothesis under its assumptions; a p-value is not the probability that a treatment works, nor does it measure the size or clinical importance of an effect. A confidence interval gives a range of values compatible with the data and model at its stated confidence level. Both are most useful when the estimate, analysis population, and method are clearly specified. The registry record does not report a primary-outcome p-value, confidence interval, or effect estimate, so none can be interpreted for this outcome.

For count or binary outcomes, precision depends on the observed count and the denominator. Small analysis populations can produce considerable uncertainty, even when the observed proportion appears notable. This is a general consideration, not a calculated claim about the study: the registry does not report the primary endpoint count or its denominator. No response proportion or uncertainty measure should be inferred from the overall enrollment figure.

What do the planning assumptions mean?

The record describes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence that this trial was randomized or had two arms. The study itself is listed as single-group, and the record does not report the sponsor’s own sample-size justification or a trial-specific design calculation. Planning sample sizes are illustrative and are not observed power.

In general, a sample-size illustration depends on its assumptions about the target effect, variability, allocation, and error rates. A normal approximation is a simplifying method whose adequacy depends on the setting and data. Over-dispersion, in general, means that observed variability exceeds what a simpler model assumes; if ignored, uncertainty can be understated. The registry record does not report an over-dispersion assessment or a model for the primary endpoint. The stated planning assumptions should not be mistaken for the analysis method used on the posted results.

What is not available for evaluating the analysis?

The registry record does not report the analysis method for the primary endpoint, missing-data rules, adjustments, or a detailed statistical plan. It does not report whether any interim analyses were planned or conducted. These details affect how an estimate should be interpreted, especially when the endpoint requires sustained measurements and the absence of rescue therapy or discontinuation. Without them, readers cannot assess how incomplete follow-up or missing components would influence responder classification.

There are no reported primary endpoint analyses in the record. Thus, statistical explanations can clarify what the endpoint and design mean, but cannot recover an effect estimate or its precision. The distinction is essential: a defined outcome and a planned method are not the same as reported results.

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("Cohort 1 (ITP) - sC5b-9 High", "Cohort 1 (ITP) - sC5b-9 Low", "Cohort 1 (ITP)")
n      <- c(3, 5, 8)
events <- c(0, 0, 0)
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  Cohort 1 (ITP) - sC5b-9 High  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 1 (ITP) - sC5b-9 Low  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Cohort 1 (ITP)  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

The study lists 19 outcome measures, including the ITP primary response endpoint and secondary outcomes in both ITP and CAD. The record does not report a multiplicity strategy. In general, testing many outcomes or subgroups can increase the chance of at least one apparently noteworthy result when each is considered separately. Prespecified priorities or statistical adjustments can address aspects of this issue, but the registry record does not say whether such procedures were planned or used. The record also does not report outcome-specific analysis results with which to assess the issue.

Missing-data handling is not reported in the registry record. That is important for a response endpoint requiring a sustained platelet threshold, no rescue therapy or prohibited medication, and no treatment discontinuation: incomplete measurements or follow-up could affect whether all conditions can be assessed. The record does not specify whether missing data were treated as non-response, excluded, imputed, or handled by another method. No particular approach should be assumed.

The primary analysis population is described as the Cohort 1 pharmacodynamic analysis set, with results intended overall and by sC5b-9 stratification group. The record does not define the membership rules for that set, report its size, or explain how it relates to all enrolled participants. It likewise does not report whether analyses used an intention-to-treat, per-protocol, or other population. These omissions limit assessment of selection and attrition, as well as the denominator underlying any response estimate.

The record lists no analysis records and does not report interim-analysis plans, stopping rules, or the reason for termination. These matters should be treated as unknown, not inferred from the study status or the absence of reported analyses.

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: haemorrhage intracranial (11.1%), headache (11.1%), blood creatinine increased (10.0%), acute kidney injury (10.0%).

For serious adverse events, the registry reports 1 affected participant among 9 at risk in Cohort 1 (ITP), 1 among 10 at risk in Cohort 2 (CAD), and 2 among 19 at risk overall. It reports no deaths. These are descriptive counts. They do not establish whether an event was caused by iptacopan, and the record does not provide a comparison group for estimating excess risk against another treatment.

The registry also lists serious-event terms with percentages: Haemorrhage intracranial and Headache at 11.1% each, and Blood creatinine increased and Acute kidney injury at 10.0% each. These listed terms should be read as registry-reported figures, not as a basis for comparing treatment groups or determining causality. The record does not give further context with those terms to establish the precise denominator or whether events overlap within participants.

A separate other-event category reports 7 affected among 9 at risk for ITP, 9 among 10 for CAD, and 16 among 19 overall. These counts are distinct from the serious-event counts in the registry record. In general, safety counts depend on how events are defined, collected, and attributed; they do not by themselves show comparative risk. No treatment-relatedness assessments or event-level details are reported in the information available.

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

The registry record establishes that this was an open-label, single-group phase 2 study of iptacopan in participants with ITP and CAD, and it gives the definition of the ITP primary response endpoint. It also reports selected safety counts. Those details can clarify what investigators intended to measure and what safety information was recorded, but they are not a substitute for efficacy results.

The primary endpoint count, response estimate, and uncertainty are not reported in the registry record. As a result, the posted results do not show how many ITP participants met the response definition or how precisely any response rate was estimated. The registry also does not report the reason for termination. The status alone does not explain why the study ended or whether the planned analyses were completed.

Even if a response count were available, this single-group design would describe outcomes among treated participants rather than provide a controlled estimate of the effect of iptacopan. The lack of a concurrent comparator means that differences from baseline or apparent improvement could not be separated from other influences using randomization. The open-label design can also affect clinical decisions and assessments, although the record does not report whether this occurred.

The safety figures are likewise descriptive. The record reports serious adverse events affecting participants and no deaths, but does not establish event causality or provide a randomized comparison. The listed serious-event terms and percentages should not be interpreted as proof of treatment-related harm or as a comparative risk estimate.

In general, clinical interpretation requires both an estimate and its uncertainty, alongside a design capable of addressing the question. For this study, the registry record supports a clear account of the planned ITP responder definition and the study structure, but not a conclusion about the size, precision, or comparative effect of treatment. It also does not support a conclusion about the reason the trial was terminated.

14. Why This Trial Matters Statistically

This study illustrates why statistical interpretation begins with the design and the question being measured. Its primary endpoint is not simply a platelet count at a single visit: it requires a threshold sustained for a specified duration and also incorporates rescue medication and treatment discontinuation. That definition makes the endpoint a composite participant-level classification. Readers need the component data and rules for incomplete observations to understand how such a classification is applied, but those details are not reported in the registry record.

The single-group design is equally important. It can describe outcomes among participants receiving iptacopan, but it cannot provide the randomized counterfactual needed for a direct treatment comparison. Calling an outcome clinically meaningful does not remove that design limitation. The term describes the endpoint definition, not the certainty of a treatment effect.

The record also highlights the difference between an endpoint being registered and results being reported. The primary question is stated, and the analysis population is identified in general terms, yet the primary count and its uncertainty are absent. Without those results, the efficacy question remains unanswered by the posted record. The listed safety counts are useful descriptive information, but cannot establish causation or comparative risk.

Finally, the study spans two disease cohorts with different outcome measures. Keeping each cohort’s question distinct avoids treating one condition as a control for the other. The record’s terminated status and missing explanation further underscore that status labels do not replace outcome reporting or a statistical account of why the study ended.

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 main trial-specific limitation is the absence of reported primary endpoint results. The registry record gives the ITP response definition but not the response count, denominator, estimate, or uncertainty. It therefore does not allow readers to assess the observed primary outcome.

The design is open-label and single-group, with no concurrent control. Any observed outcome in treated participants would be descriptive rather than a randomized comparison. The ITP and CAD cohorts have different conditions and outcome measures, so they do not form a like-for-like comparison. The registry does not report details that would allow assessment of masking safeguards or independent outcome adjudication.

The endpoint population is described as the ITP pharmacodynamic analysis set, but its size and membership rules are not reported. The record does not give the sC5b-9 stratum sizes or results. It also does not explain how missing platelet measurements, rescue therapy, prohibited medication, or treatment discontinuation were handled for analysis. Those details matter because each is connected to the responder definition.

The record lists 19 outcome measures but does not report a multiplicity strategy, detailed statistical plan, or outcome analyses. The reason for termination, interim-analysis information, and sponsor sample-size justification are not reported in the registry record. The available safety information is limited to selected counts and listed serious-event terms; event-level details and causal assessments are not reported. These limitations restrict efficacy interpretation, precision assessment, and safety attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Basket Study to Assess Efficacy, Safety and PK of Iptacopan (LNP023) in Autoimmune Benign Hematological Disorders — NCT05086744.
• Registry record last updated 2025-10-16; status last verified 2025-10.
• Results first posted 2025-03-19.
• 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

NCT05086744 is a phase 2, open-label, multi-center, single-group study of iptacopan 200 mg twice daily in participants with primary ITP and primary CAD. The registry reports enrollment of 19 participants, a start date of 2021-12-21, a primary completion date of 2023-09-20, and a terminated status. The reason for termination is not reported in the registry record.

The primary endpoint is the number of participants in the ITP pharmacodynamic analysis set meeting a clinically meaningful response definition during up to 12 weeks of Part A. The record does not report the primary endpoint result, its denominator, or an uncertainty estimate. It lists 19 outcome measures and no analysis records.

For safety, the registry reports serious adverse events affecting 1 participant in each cohort and 2 overall, with no deaths. The study has no randomized comparator, and the reported safety counts are descriptive. Missing-data handling, multiplicity methods, and a detailed statistical plan are not reported in the registry record.