Nevanimibe HCl for the Treatment of Classic CAH: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nevanimibe HCl for the Treatment of Classic CAH (NCT03669549), a na phase 2 study. The primary outcome is Percentage of Subjects Achieving Serum 17-OHP Targets.

2. Clinical Question

The clinical question was whether patients with classic congenital adrenal hyperplasia could achieve specified serum 17-OHP targets during treatment with ascending doses of oral nevanimibe hydrochloride. The primary endpoint was defined as the percentage of patients meeting the applicable target through Day 113, with target thresholds depending on sex and, for premenopausal women, menstrual-cycle phase.

The target definitions differ across the listed groups. For men and postmenopausal women, the threshold is 17-OHP ≤ 2x ULN. For premenopausal women, the threshold is phase-specific: during the follicular phase, 17-OHP ≤ 2x follicular phase ULN; during the luteal phase, 17-OHP ≤ (2x follicular phase ULN + (luteal phase ULN - follicular phase ULN)). These definitions make the endpoint a threshold-based response measure rather than a common raw concentration threshold applied to everyone.

The study does not establish a randomized contrast between nevanimibe and another treatment or control. Its question is therefore about target attainment during the study’s dose-titration regimen, not a comparative treatment effect against an untreated or active-control group.

3. Trial Design

The registry describes a multicenter, open-label, single-group Phase 2 study with intra-subject dose titration. Participants received ascending dose levels of oral nevanimibe hydrochloride, beginning with 500 mg BID and titrating up to 2000 mg BID. Because the study is single-group and not randomized, the dose-level categories should not be read as independent, randomized treatment arms. Allocation is recorded as NA, and masking is recorded as NONE.

The planned sequence included a Screening Period of approximately 2-14 weeks, a Baseline Period of approximately 2-8 weeks, and a 16-week Treatment Period. The record states that the anticipated overall duration per subject would range from 24-42 weeks. The primary endpoint timeframe is through Day 113. These are descriptions of the study schedule; they do not indicate that every participant completed each period or had endpoint data available.

The registry lists enrollment as 15 and gives a primary completion date of 2020-06-03. The study status is TERMINATED. The registry record does not report the reason for termination, whether the planned treatment period was completed as intended, or whether follow-up continued after the primary completion date.

The dose-level safety groups have different numbers at risk, and the record describes participants moving through ascending doses. Consequently, dose-level counts do not represent a set of parallel groups assigned at baseline. Exposure and the opportunity to contribute observations may differ across dose levels. A comparison of counts across those levels would not, on its own, isolate a dose effect.

The record lists one primary outcome measure and no analyses. It does not give cohort definitions, detail how participants were allocated to cohorts, or describe a control condition. It also does not report a protocol-based sample-size justification. The registry’s broad description of the design supports interpretation as a dose-titration study, not as a randomized comparative trial.

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: Screening Period of 2-14 weeks After signing informed consent, patients with classic CAH entered the Screening Period to assess preliminary eligibility for the study based on the inclusion and exclusion criteria. In addition, pertinent information was collected such as past medical history, demographic data, and prior and current medications.

Overall Study

Reasons for not completing this period:

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 Percentage of Subjects Achieving Serum 17-OHP Targets, measured over Through Day 113.

The primary endpoint is the percentage of subjects achieving serum 17-OHP targets through Day 113. It is described as an overall response rate within each cohort. A participant meets the endpoint by satisfying the threshold applicable to their sex and, for premenopausal women, the relevant cycle phase.

This type of endpoint converts a laboratory measurement into a defined response category. In general, a threshold-based endpoint can make a result easier to interpret against a stated target, but it also discards information about how far a measured value lies above or below the threshold. A participant just within the target and a participant well within it both count as achieving the target under this definition. The endpoint does not, by itself, describe the distribution or change in continuous 17-OHP values.

The sex- and phase-specific rules matter to interpretation: the same measured value need not imply the same response classification for every participant. The criteria for men and postmenopausal women use 2x ULN, while the premenopausal-women criteria use follicular- or luteal-phase ULN terms. The registry does not report how phase was determined when classifying an individual result, how repeated measurements were handled, or how observations that could not be classified were treated.

The measure is labeled with a percent unit, while its parameter type is recorded as NUMBER. Whatever the metadata convention, the endpoint description defines the intended outcome as a percentage. No observed response percentage, numerator, denominator, confidence interval, or analysis result is reported in the registry record, so the magnitude and precision of target attainment cannot be assessed from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a proportion-type outcome: each evaluated participant is classified as meeting or not meeting a predefined serum 17-OHP target, and the endpoint description calls for the percentage meeting the target within each cohort. In general, this approach is useful when a clinical question is framed around crossing a threshold. It is different from analyzing the measured laboratory value as a continuous outcome, which would retain information about the size and direction of individual values.

The target rules are not uniform across all participants. The registry defines the criterion for men and postmenopausal women as 17-OHP ≤ 2x ULN. For premenopausal women, it defines a follicular-phase threshold of 17-OHP ≤ 2x follicular phase ULN and a luteal-phase threshold of 17-OHP ≤ (2x follicular phase ULN + (luteal phase ULN - follicular phase ULN)). This makes classification dependent on the applicable subgroup and phase. The record does not explain how these categories were assigned in practice or how a missing cycle-phase classification would affect analysis.

A response percentage is most interpretable when its denominator is clear. The denominator should correspond to the population used for the endpoint analysis, not simply the number enrolled. The registry lists enrollment as 15 but does not report the number analyzed for the primary outcome, the number with endpoint measurements, or the handling of participants who discontinued or lacked a measurement. Thus, no endpoint percentage can be reconstructed from the record.

In general, confidence intervals communicate uncertainty around an estimated response proportion. Their width depends on the amount of information in the data and on the analysis method. A narrow interval indicates greater precision under the method’s assumptions; a wide interval indicates more uncertainty. Since the registry does not report a response estimate or interval, precision cannot be evaluated. There is also no reported p-value for the primary endpoint.

The study is described as a single-group intra-subject dose-titration design. This feature is important for methods: dose-level observations are not equivalent to independent, randomized arm-level outcomes. The same participant may contribute observations while moving through ascending dose levels, and the counts at risk vary by level. In general, repeated measurements from the same participant may be statistically related. An analysis that treats correlated observations as independent can misstate uncertainty. The registry record does not report whether the endpoint analysis accounted for repeated observations, nor does it specify an analysis model.

For the same reason, a simple contrast between the reported dose-level safety counts would not establish a causal dose effect. General comparisons require attention to the mechanism that determined which participants reached each level, the time exposed at each dose, and differences in the participants contributing data. The registry does not report an adjustment strategy or a formal dose-response analysis. No statistical result should be inferred from the order of the dose categories alone.

The registry lists no analyses. This means the record does not supply an analysis method for the primary endpoint, a model for repeated observations, or a method for missing data. It also does not report whether the endpoint was analyzed by cohort, whether any subgroup analyses were planned, or how the word “overall” was operationalized across cohorts. The definition says the response rate was within each cohort, but cohort construction is not described in the available record.

Some registry planning assumptions describe a two-arm illustration with equal allocation, a two-sided significance level of 0.05, and a normal approximation. The illustration is described as based on a fraction of an observed effect, with sample sizes stated per arm for non-time-to-event outcomes. These are planning assumptions, not the design of this single-group study, and they are not observed power. The registry does not report a trial-specific sample-size justification. Without a reported primary effect estimate, such a planning illustration cannot be treated as a result of the trial.

For adverse events, the record provides counts at risk and counts affected within dose-level categories. In general, event counts are descriptive and do not capture all relevant aspects of safety, including duration of exposure or uncertainty around rates. The record does not report person-time, a comparative safety model, or a control group. The dose-level count categories should therefore be read as registry summaries of recorded events, not as formal estimates of relative risk.

These method distinctions separate three questions: what outcome was defined, what data were collected and analyzed, and what can be inferred from the analysis. The endpoint definition is available; the efficacy data and analysis are not reported in the registry record. Consequently, the statistical information is insufficient to quantify target attainment or its precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no analyses. It does not describe a multiplicity procedure, such as how statistical error would be controlled across multiple endpoints, cohorts, subgroup tests, or repeated looks at accumulating data. A multiplicity plan is not automatically required for every descriptive endpoint, but its absence from the record means readers cannot determine whether or how multiple statistical claims were planned to be managed.

The endpoint is defined as an overall response rate within each cohort, while the cohort definitions and number of cohort-specific analyses are not reported. The record therefore does not clarify whether the endpoint would yield separate estimates, a combined estimate, or both, nor whether any formal testing was planned. No p-values or confidence intervals are reported for the primary endpoint.

Missing-data methods and analysis populations are also not described. The registry does not state whether the primary analysis would include all enrolled participants, participants who received treatment, or those with an observed Day 113 assessment. It does not explain how discontinuation, missed measurements, or unclassifiable phase-specific results would be handled. These choices matter for a threshold-response endpoint because excluding participants without an outcome can change the population represented by the response percentage.

Interim analyses, stopping rules, and any prespecified statistical analysis plan are not reported in the registry record. The terminated status does not identify whether an interim analysis occurred or why the study stopped. No assumption about the missing analysis or missing observations can be substituted for a documented method.

11. 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: uroinfection (7.1%).

The registry reports serious adverse event counts by nevanimibe dose level. The counts at risk and serious-event counts are 14 and 0 for <500 mg BID; 5 and 0 for 500 to <1000 mg BID; 14 and 1 for 1000 to <1500 mg BID; 9 and 0 for 1500 to <2000 mg BID; and 9 and 0 for 2000 mg BID. Deaths are reported as 0 in each dose-level category. The registry lists Uroinfection at 7.1% among the top serious terms.

These categories belong to an ascending, intra-subject dose-titration study, not to randomized parallel groups. Their at-risk counts differ, and the record does not report exposure duration or person-time by level. The counts therefore should not be read as directly comparable rates or as proof that a dose level is safer or less safe than another. Zero recorded serious events at a dose level does not establish absence of risk.

The record also reports other-event counts of 3, 5, 8, 7, and 5 across the dose levels in ascending order. These are descriptive counts, not comparative estimates. The registry does not provide event-level detail for these counts in the listed summary. Safety interpretation is limited by the single-group design, the absence of a control group, and the lack of a reported statistical safety analysis.

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

The registry record establishes that a Phase 2, multicenter, open-label study evaluated ascending doses of nevanimibe hydrochloride in classic congenital adrenal hyperplasia. It also specifies a primary endpoint based on achieving serum 17-OHP targets through Day 113. These design and endpoint details clarify what the study set out to examine.

The record does not report the primary efficacy outcome. No target-response percentage, endpoint denominator, confidence interval, or inferential result is listed. Therefore, it is not possible to determine from the posted record how often participants reached the target or how precisely that response was estimated. The absence of an efficacy result in this record is not evidence that the endpoint was or was not achieved.

The study also does not provide a randomized control comparison. Its single-group intra-subject titration design cannot, by itself, separate changes associated with the study drug from other changes over time or from factors affecting which dose levels participants reached. Dose-level event counts are descriptive and should not be interpreted as controlled comparisons.

The reported safety summaries include serious adverse event counts, other-event counts, deaths, and a listed serious-event term. These data describe what the registry records for the dose-level categories. Without a comparator, exposure-adjusted analysis, or full event context, they do not quantify comparative risk or establish a causal relationship between a particular dose and an event.

The TERMINATED status is important context, but the reason for termination is not reported in the registry record. It cannot be used to infer that the study stopped for safety, lack of efficacy, or any other specific reason. Likewise, the enrollment figure does not show how many participants contributed primary endpoint data. The results available in the registry are insufficient to support a claim about clinical benefit or lack of benefit.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why design and analysis must be read together. The primary endpoint is clearly described as a target-response percentage, but the registry record does not report the observed response or its uncertainty. A precise endpoint definition is not a substitute for the estimate and analysis needed to interpret the result.

The intra-subject dose-titration design also illustrates why dose categories should not automatically be treated as trial arms. Participants were described as receiving ascending doses, and the number at risk varies across the dose levels. In general, data from people observed at more than one dose can be correlated, while access to later dose levels may depend on study progression. Statistical methods need to respect those features if the goal is to estimate a dose relationship. No such method is reported.

The endpoint’s subgroup-specific thresholds raise another general issue: a response proportion can combine classifications based on different rules. Clear reporting of cohort definitions, denominators, missing observations, and subgroup-specific results is needed to understand what the overall response rate represents. Those details are not reported in the registry record.

Finally, the record distinguishes design information from evidence of an observed effect. Planning assumptions involving a two-arm, equal-allocation illustration do not describe this single-group trial’s actual allocation, and such calculations are not observed power. The absence of a control group and the absence of primary efficacy analyses mean the statistical record supports a description of the question and design, but not a comparative conclusion about treatment effect.

14. 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.

Several limitations specific to this trial follow from the registry information. The study is open-label and single-group, with intra-subject ascending dose titration. It has no reported randomized comparator, so changes over time and differences in who reached each dose level cannot be separated from a treatment effect using a controlled contrast. Dose-level summaries are not like-for-like comparisons.

The study status is TERMINATED, but the reason for termination is not reported in the registry record. The record lists a primary completion date, but does not explain completeness of follow-up, whether planned enrollment or treatment was completed, or how termination affected data collection. These uncertainties matter when interpreting the lack of posted efficacy analyses.

The primary endpoint is defined, but the registry does not report the response estimate, denominator, confidence interval, or analysis method. Nor does it report cohort definitions, analysis populations, handling of missing measurements, or how phase-specific classifications were made. Without these elements, the endpoint cannot be independently evaluated for completeness or precision.

Safety reporting is also descriptive. The counts are presented by dose level, with varying numbers at risk, and the study has no reported control group or exposure-adjusted safety analysis. The available counts cannot establish comparative safety. The reason for termination and any relationship to efficacy or safety are not reported.

The record does not report a trial-specific sample-size justification or statistical analysis plan. Planning assumptions described for a two-arm illustration do not match the single-group design and should not be mistaken for the study’s design or observed power. Collectively, these limitations restrict interpretation to the stated study design and recorded adverse-event summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Nevanimibe HCl for the Treatment of Classic CAH — NCT03669549.
• Registry record last updated 2021-03-04; status last verified 2021-02.
• Results first posted 2021-03-04.
• 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.

18. Record Summary

NCT03669549 is a Phase 2, multicenter, open-label, single-group study of nevanimibe hydrochloride for classic congenital adrenal hyperplasia. The registry describes intra-subject ascending oral doses from 500 mg BID up to 2000 mg BID, with a 16-week Treatment Period. Enrollment is listed as 15, and study status is TERMINATED.

The primary endpoint is the percentage achieving specified serum 17-OHP targets through Day 113, with thresholds dependent on sex and, for premenopausal women, cycle phase. No primary efficacy result or analysis is reported. Safety summaries list serious and other adverse-event counts by dose level, zero deaths in each category, and Uroinfection at 7.1% among the top serious terms. The termination reason, missing-data methods, analysis populations, and statistical plan are not reported in the registry record.