Assessment of BIM23B065, Given as Repeated Subcutaneous Injection in Subjects With Acromegaly: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment of BIM23B065, Given as Repeated Subcutaneous Injection in Subjects With Acromegaly (NCT03045302), a na phase 2 study. The primary outcome is The Number of Subjects Who Were Growth Hormone (GH) Responders at Day 14 of the Treatment Period.

2. Clinical Question

3. Trial Design

The registry describes NCT03045302 as a Phase IIa, open-label, single-arm, two-stage, multicentre study investigating the pharmacodynamics, pharmacokinetics, safety, and tolerability of repeated subcutaneous BIM23B065 in subjects with acromegaly. The registered phase is Phase 2. Ipsen is listed as the sponsor. The study began on 2017-01-26, and the primary completion date is 2017-05-17. Its status is terminated; a reason for termination is not reported in the registry record.

Enrollment is listed as 4. Because the study had one treatment group and no control group, the design is descriptive rather than a randomized comparison. Open-label means masking was not used, as also indicated by the registry’s masking entry. The registry title identifies a two-stage design, but details about the stages, including how progression between stages was decided or whether the second stage began, are not reported in the registry record.

The intervention is BIM23B065, given by repeated subcutaneous injection. The primary endpoint description refers to a 6-day titration and an 8-day treatment period, with growth hormone measured at baseline on Day -1 and again on Day 14. The registry does not report the full treatment schedule or the planned conduct of the pharmacokinetic and safety assessments.

The registered enrollment is small, and the available efficacy population may differ from the enrolled group because the endpoint applies eligibility conditions for evaluable pharmacodynamic data. The number meeting those conditions is not reported in the registry record. With no concurrent control group, observed changes cannot be separated from other time-related or measurement-related influences using a between-group treatment contrast.

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: 7 subjects were screened and 3 failed screening (1 subject did not meet eligibility criteria and 2 subjects did not complete screening procedures due to the early study termination).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Efficacy Evaluable population consisted of all subjects with at least 1 BIM23B065 administration with available pharmacodynamic (PD) data and no protocol deviations with relevant impact on PD data, who had an evaluable primary efficacy endpoint (mean concentration of GH over 6 hours) at baseline and at Day 14.

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 Intent to treat population consisted of all subjects with at least 1 BIM23B065 administration.

6. Primary Endpoint

The registry lists the primary outcome as The Number of Subjects Who Were Growth Hormone (GH) Responders at Day 14 of the Treatment Period, measured over From baseline (Day -1) to Day 14..

The primary endpoint is the number of subjects who were growth-hormone responders at Day 14 of the treatment period. The registry defines a responder as a subject whose mean serum growth hormone concentration was at most 2.5 micrograms per litre, or whose mean concentration had fallen by more than 50% from the mean baseline concentration. Mean concentration was measured over 6 hours at baseline on Day -1 and on Day 14. The response definition therefore combines an absolute concentration criterion with a relative-change criterion.

A responder count is a binary-outcome summary: each subject either meets the stated definition or does not. In general, a count can communicate how many participants met a prespecified clinical or biological threshold, but its interpretation depends on knowing both the count and the population assessed. The registry record does not report the number of responders, the number assessed for this endpoint, or an uncertainty interval for the count. It is therefore not possible to quantify the observed response frequency from this record.

The endpoint is relevant to the study’s stated pharmacodynamic purpose because it classifies participants according to growth hormone measurements after treatment. The record does not explain why this particular threshold was selected, whether it was the sole efficacy measure considered in the protocol, or how a missing Day 14 measurement was handled. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study has a single-group design, so its main endpoint is a count of participants meeting a defined response rule rather than an estimate of the difference between treatment and control groups. The endpoint is binary at the participant level: a person meets the responder definition or does not. The registry record does not post the observed responder count, the denominator evaluated, or any statistical analysis of that endpoint.

What does a responder count represent?

A count records how many participants satisfy a specified criterion. In general, a proportion is often used to relate that count to the number assessed, while a confidence interval describes uncertainty around an estimate. Neither an endpoint proportion nor a confidence interval can be reconstructed from the registry record because the response count and evaluable denominator are not reported. No additional numerical estimate should be inferred from the enrollment figure alone.

The response rule uses two alternatives: an absolute mean serum growth hormone threshold of at most 2.5 micrograms per litre, or a reduction of more than 50% from the mean baseline concentration. In general, a rule using “or” classifies a participant as a responder if either condition is met. The registry does not report how many participants met each condition separately, or whether any participants met both.

Why does the study design matter?

In general, a single-arm study can describe outcomes observed among participants who received the intervention, but it cannot estimate a treatment contrast against a concurrent control group. A change from baseline may reflect treatment, natural variation, measurement variation, or other influences. Without a comparator, these explanations cannot be distinguished by a randomized between-group comparison. This is a design limitation, not evidence for or against a treatment effect.

Open-label means masking was not used. In general, lack of masking can affect expectations, reporting, or assessment, depending on the outcome and how it is measured. The registry record does not describe additional safeguards or assessment procedures that would allow their influence to be evaluated. The endpoint is based on serum measurements, but laboratory procedures and assessor arrangements are not reported in the registry record.

What can an uncertainty interval tell a reader?

In general, a confidence interval gives a range of values compatible with the data under a specified statistical method and its assumptions. It communicates precision as well as the central estimate; it is not a guarantee that the true value lies in that particular interval. No interval is reported for the primary endpoint, and no underlying response count is posted. Accordingly, precision cannot be assessed from the registry record.

For a binary endpoint, the choice of interval method can matter, particularly when the number of observations is small or the observed count is near an endpoint of the possible range. In general, methods differ in their coverage and assumptions. The registry does not identify a method for estimating uncertainty, and there is no posted result to which one could apply it.

What is not reported about statistical planning?

The registry record does not report a sample-size justification, a target number of participants for the efficacy population, or a statistical analysis plan. It also does not report any interim analysis or the rules governing the two stages named in the study title. These omissions mean that the intended precision, decision criteria, and role of stage progression cannot be assessed from the registry record. A planning illustration based on an observed effect, if presented elsewhere in the statistical materials, should be treated as hypothetical planning rather than as observed power. It does not replace the trial’s own design rationale, which is not reported in the registry record.

In general, “observed power” calculated after a study from its observed effect is not a substitute for reporting an estimate with an uncertainty interval. It is also important to distinguish planning assumptions from outcomes actually measured. No calculated sample-size results or endpoint estimate are stated in the registry record.

How should the analysis population be interpreted?

The endpoint description defines an Efficacy Evaluable population using treatment exposure, available pharmacodynamic data, absence of relevant protocol deviations, and an evaluable baseline measurement. In general, analysis-population rules specify which participants contribute to an estimate. Different rules can produce different denominators and may affect interpretation if inclusion depends on post-enrollment information. The number in this population, reasons for exclusions, and relationship between this population and the enrolled group are not reported in the registry record.

The endpoint timeframe is baseline on Day -1 through Day 14, and the description refers to a 6-day titration and an 8-day treatment period. The record does not explain the handling of missing measurements, repeat measurements, or protocol deviations beyond the stated population criterion. No imputation method, sensitivity analysis, model, or adjustment strategy is reported. Since no analysis is posted, there is no basis to describe an implemented statistical procedure or verify whether it followed a prespecified plan.

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("BIM23B065 BID Stage 1")
n      <- c(3)
events <- c(1)
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  BIM23B065 BID Stage 1  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified as the number of growth-hormone responders at Day 14. The registry record lists one outcome measure and zero analyses. It does not report whether other outcomes were tested statistically, whether the primary endpoint was selected from a larger set of possible outcomes, or whether any multiplicity procedure was planned. The two-stage design is named, but stage-specific decision rules and any interim-testing plan are not reported in the registry record.

In general, multiplicity arises when several hypotheses or outcomes are tested, because repeated testing can increase the chance of at least one nominally positive finding. Procedures for managing that issue depend on the analysis plan and testing structure. No such procedure is described in the registry record, so it is not possible to say whether multiplicity was addressed or relevant to any completed analysis.

The Efficacy Evaluable population is defined by treatment exposure, availability of pharmacodynamic data, absence of protocol deviations considered relevant to those data, and an evaluable baseline measurement. The size of this population and the number with an evaluable Day 14 measurement are not reported in the registry record. The record does not describe whether all enrolled participants were included in any analysis, or whether alternative analysis populations were used.

Missing-data handling is also not reported in the registry record. There is no information about the number or reasons for missing measurements, imputation, sensitivity analyses, or assumptions about missing outcomes. These details matter in general because conclusions from an endpoint may depend on which participants have observed measurements and how missing outcomes are treated. With no posted endpoint count or analysis, the impact of missing data 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 0% reporting threshold.

Most frequent non-serious adverse event terms

For the BIM23B065 BID Stage 1 group, the registry lists 4 subjects at risk for serious adverse events and 0 affected. It lists 4 subjects at risk for other adverse events and 2 affected. No serious adverse-event terms are listed. These are counts reported for the group, not estimates from a comparison with an untreated or active-control group.

In general, “at risk” indicates the group used as the denominator for an adverse-event category, while “affected” counts participants recorded with at least one event in that category. The registry does not provide event-level details for the two participants with other adverse events, such as event type, timing, severity, outcome, or whether events were considered related to treatment. The record also does not explain whether “other” is further divided into specific categories.

The group is small, so these counts should be read as descriptive observations from this study rather than as precise estimates of safety in a broader population. The absence of recorded serious events among four participants does not establish that serious events cannot occur, and the other-event count does not establish causation. No medical conclusion about treatment safety can be drawn from these figures alone.

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

The registry record establishes that the study set out to assess repeated subcutaneous BIM23B065 in subjects with acromegaly and defined a Day 14 growth-hormone responder endpoint. It also documents a Phase IIa, open-label, single-arm, two-stage, multicentre design, enrollment of 4, and a terminated status. These are details about the registered study and its reporting.

The record does not report how many participants met the responder definition, how many were evaluated for that endpoint, or a statistical estimate of response. It therefore does not show the observed response frequency or how precise that frequency might be. The absence of a posted endpoint result is not evidence that no participants responded, and it is not evidence that all participants responded.

Because there is no comparator group, the design cannot provide a randomized estimate of the difference between BIM23B065 and another treatment or control condition. In general, an outcome observed after treatment in a single group does not by itself establish what would have happened to those participants without the intervention. The registry record contains no analysis that addresses this limitation.

The safety entries record zero participants affected by serious adverse events and two affected by other adverse events among four at risk in the listed group. These observations describe only the reported group and do not establish whether events were caused by treatment. The registry does not provide the event details needed for a fuller account.

The intended pharmacodynamic, pharmacokinetic, safety, and tolerability objectives are stated in the study description, but results for those objectives are not comprehensively reported in the registry record. The primary endpoint definition and limited safety counts can describe what was planned and what was recorded, but they cannot support a conclusion about the magnitude, reliability, or comparative effect of treatment.

14. Why This Trial Matters Statistically

This trial is statistically instructive because the registry states a specific binary endpoint while leaving its observed value unreported. A clear endpoint definition is necessary for interpreting a result, but it does not replace the result itself. Without a responder count and the number assessed, readers cannot estimate the frequency of response or its uncertainty.

The design also illustrates the distinction between describing outcomes and estimating comparative effects. A single-arm study can record what happened among participants receiving the intervention, but without a concurrent comparator it cannot isolate a treatment contrast. This distinction remains important even when the outcome is objectively defined: a measurement-based endpoint does not by itself create a control condition.

Enrollment of 4 highlights why the denominator and analysis population matter. The registry’s Efficacy Evaluable definition includes several conditions beyond enrollment, so the endpoint population cannot be assumed to match the enrolled group. The actual evaluable count is not reported in the registry record. In general, small samples also make estimates sensitive to individual observations and can leave substantial uncertainty.

The two-stage description, terminated status, and lack of posted statistical analyses raise questions about the intended decision structure and the completeness of outcome reporting. The record does not answer whether the second stage proceeded, why the study was terminated, or what statistical plan governed any analyses. These gaps do not establish that the study was conducted improperly; they limit what can be evaluated from the registry record.

The safety counts offer a further lesson in interpretation: small descriptive counts should not be treated as comparative evidence or as precise estimates of risk. Taken together, the record shows why design, analysis populations, missing-data information, and complete outcome reporting are all needed for sound statistical interpretation.

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 limitation for interpreting efficacy is that the primary responder count is not reported in the registry record. The number of participants evaluated for the endpoint is also absent, despite the defined Efficacy Evaluable population. Without those details, neither the observed response frequency nor its precision can be assessed.

The single-arm design has no concurrent control group. As a result, the record cannot support a randomized comparison or distinguish an observed change from other influences. The study is open-label, and the registry does not describe masking or other assessment safeguards. The endpoint is based on serum growth hormone measurements, but laboratory methods and measurement-quality procedures are not reported.

Enrollment is listed as 4, limiting the amount of information available for estimating outcomes. The record does not report a sample-size justification, intended precision, or the size of the efficacy population. The trial is described as two-stage, but stage-specific conduct and progression criteria are not reported. Its terminated status is stated, but the reason and consequences for data collection are not given.

Statistical analysis details are sparse: the registry lists zero analyses and does not report an analysis plan, uncertainty estimates, missing-data methods, sensitivity analyses, or multiplicity procedures. The safety information is also limited to participant counts, with no serious-event terms and no details about the other adverse events. These omissions constrain interpretation and do not, on their own, establish why information is absent or what the unreported results were.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessment of BIM23B065, Given as Repeated Subcutaneous Injection in Subjects With Acromegaly — NCT03045302.
• Registry record last updated 2019-03-08; status last verified 2019-03.
• Results first posted 2019-03-08.
• 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

NCT03045302 is a Phase IIa, open-label, single-arm, two-stage, multicentre study of repeated subcutaneous BIM23B065 in subjects with acromegaly. Ipsen is listed as sponsor; enrollment is 4, and the status is terminated. The primary endpoint is the number of growth-hormone responders at Day 14, using an absolute concentration threshold or a reduction from baseline.

The registry record does not report the responder count, the size of the Efficacy Evaluable population, or any statistical analysis. In the listed BIM23B065 BID Stage 1 safety group, 0 of 4 subjects were affected by serious adverse events and 2 of 4 were affected by other adverse events. No serious-event terms are listed. The reason for termination, missing-data approach, sample-size justification, and detailed analysis plan are not reported in the registry record.