Study to Evaluate the Safety and Efficacy of SPR001 in Subjects With Classic Congenital Adrenal Hyperplasia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety and Efficacy of SPR001 in Subjects With Classic Congenital Adrenal Hyperplasia (NCT03687242), a na phase 2 study. The primary outcome is The Incidence of Treatment-emergent Adverse Events (Safety and Tolerability) in Subjects With CAH.

2. Clinical Question

The primary question is about safety and tolerability, not a comparison of SPR001 with another treatment. In a single-group study, the registry can describe the events reported among participants exposed to SPR001, but it cannot directly contrast their event experience with a concurrent control group. The record lists change from baseline in 17-hydroxyprogesterone (17-OHP), androstenedione (A4), and adrenocorticotropic hormone (ACTH) as secondary outcomes. Those measures address biochemical changes; the primary endpoint instead counts participants with treatment-emergent adverse events.

The record gives an enrollment of 11. For the primary endpoint, the stated population is participants who received at least one dose, and the safety figures give 11 participants at risk. These descriptions identify the group used for the reported safety counts, but do not establish how complete follow-up was for every participant. The registry record does not report a control-based question or a causal estimate of treatment effect.

3. Trial Design

The study is listed as Phase 2 and completed. Its title describes a 3-Month evaluation of the safety and efficacy of SPR001 in subjects with classic congenital adrenal hyperplasia. The brief description says eligible subjects received 12 weeks of open-label treatment. The intervention is SPR001 at Dose A.

The design is single-group, and masking is listed as none. Allocation is recorded as NA. The registry explicitly notes that the study is not a randomized comparison and that its arms are not a like-for-like control comparison. In this record, the listed SPR001 group is therefore an exposed group, not one side of a randomized treatment contrast. There is no concurrent comparator in the design details.

Enrollment is 11. The study start is recorded as 2018-09-06, and primary completion as 2019-07-08. These dates describe the registry timeline; they do not establish the duration of an individual participant’s observation or explain any gaps in follow-up. The planned treatment period is stated as 12 weeks, while the primary endpoint timeframe is also stated as over 12 weeks.

Three secondary outcomes are listed: change from baseline in 17-OHP, A4, and ACTH. The record lists four outcome measures in total, but no outcome analyses are listed. It does not report the study’s sample-size justification, details of follow-up after treatment, or a fuller statistical analysis plan. The available design description supports an account of the study structure and recorded endpoint, but not reconstruction of unreported operational or analytical choices.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who received at least one dose of study drug.

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: All enrolled subjects who received at least one dose of study drug. This population is the primary analysis set for all efficacy and safety analyses.

6. Primary Endpoint

The registry lists the primary outcome as The Incidence of Treatment-emergent Adverse Events (Safety and Tolerability) in Subjects With CAH, measured over Over 12 weeks.

The primary endpoint is the incidence of treatment-emergent adverse events in participants with CAH. Its stated measure is a count of participants, and its timeframe is over 12 weeks. The endpoint description includes any serious adverse events, dose-limiting toxicities, and adverse events leading to discontinuation of study drug. The population is participants who received at least one dose.

Counting participants with an event answers a practical safety question: how many participants in the defined group had an event during the stated observation period? This differs from counting the total number of event episodes. A participant-level count does not show how many events each affected participant experienced, how long events lasted, or how severe non-serious events were. Those details are not reported in the registry record for this primary outcome.

General statistical context: safety outcomes are commonly described with counts because the presence of an event is directly interpretable. In a small single-group study, the count should be read alongside its denominator and the endpoint definition. It describes what was recorded in the treated group during the specified period; without a comparator, it does not by itself estimate how event frequency would differ under another treatment or no study treatment.

The registry separately reports serious and other adverse-event counts. These categories should not be added together or treated as a complete description of event burden unless their definitions and overlap are known. The record does not report whether the categories are mutually exclusive at the participant level.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: the central distinction in this study is between describing a single treated group and estimating a treatment contrast. The record lists a single-group model, no masking, and allocation as NA. As a result, the primary safety count has no concurrent randomized group as a reference. The figures describe participants in the SPR001 group; they do not quantify a difference between treatment strategies.

What does a participant count represent?

The primary endpoint uses a count of participants with treatment-emergent adverse events. A participant is counted as affected if the endpoint’s event definition is met during the stated timeframe. This type of measure is different from an event count: a person with multiple events may still contribute only once to a participant-level count. The registry’s primary outcome description does not provide event totals or participant-level histories, so those cannot be reconstructed from the reported counts.

For interpretation, a count is meaningful together with its denominator and population definition. The record defines the endpoint population as participants who received at least one dose, while the safety results list 11 participants at risk for both serious and other adverse events. The enrollment is also 11. The record does not provide further detail about withdrawals, missing event assessments, or whether all participants completed the full observation period.

Why does the absence of a control matter?

General statistical context: a randomized control group can help distinguish treatment-associated patterns from background event rates and other influences, because groups are compared under a defined allocation process. This study has no such comparison. Its open-label status means participants and study personnel were not masked, as recorded in the design. In general, awareness of treatment can influence reporting or assessment, although the registry record does not state whether or how this occurred in this study.

A single-group count can still document what was recorded during exposure. It cannot, by itself, attribute every event to the study drug, nor can it indicate what would have happened to the same participants under another treatment. The record’s own note that this is not a randomized comparison is important when interpreting the results.

What can uncertainty estimates add?

General statistical context: a confidence interval describes the range of values compatible with data under a specified statistical method and assumptions. It can communicate precision that a point estimate alone does not. For a small participant group, uncertainty around an event proportion or count can be substantial, particularly when the number of events is low. No confidence interval or other uncertainty estimate for the primary endpoint is listed in the registry record, so none can be quoted.

The record lists zero participants with serious adverse events. A zero observed count is not equivalent to a precisely known zero underlying risk. Statistical uncertainty remains, and a comparator-based estimate is unavailable. The record also does not report a statistical method for handling event timing or differing observation duration.

How should the sample-size assumptions be read?

The registry record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between 2 arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a description of this study’s single-group design. The record says that non-time-to-event illustrations are expressed as participants per arm and time-to-event illustrations as total events. No sample-size illustration values are available in the registry record described for this analysis, and the study’s own sample-size justification is not reported.

General statistical context: a sample-size calculation depends on assumptions about the target effect, variability or event frequency, significance level, power, and design. A planning calculation is conditional on those inputs; it does not show that a study had a particular probability of detecting an effect after the fact. It should not be described as observed power. The assumptions listed for the illustration do not transform this single-group trial into a two-arm comparison.

What does the analysis record contain?

The registry lists four outcome measures and no outcome analyses. This means the registry record does not provide analysis results for those outcomes. It does not establish whether analyses were performed outside the registry or whether results are available elsewhere. No adjustment method, model specification, missing-data approach, or multiplicity strategy is reported in the registry record. Statistical interpretation should therefore stay with the descriptive counts that are actually listed and avoid implying an unreported inferential analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary safety endpoint and three secondary outcomes: change from baseline in 17-OHP, A4, and ACTH. Four outcome measures are listed in total, while no outcome analyses are listed. The registry record does not report a multiplicity strategy, such as whether secondary outcomes were treated as exploratory, whether testing was adjusted, or how any family of hypotheses was defined. Without that information and without posted analyses for these measures, the secondary outcomes cannot be interpreted as confirmatory statistical findings.

The record also does not report a missing-data plan. It does not say how missing laboratory measurements, incomplete follow-up, or withdrawals were handled. The primary endpoint population is described as participants who received at least one dose, and the safety summaries list 11 participants at risk. Those details do not reveal whether every scheduled observation was available or how missing observations, if any, were classified.

General statistical context: missing data can affect estimates when the participants with observed measurements differ from those without them. The consequences depend on why data are missing and on the analysis approach. Multiplicity also matters when several outcomes are examined, because repeated testing can increase the chance of at least one apparently unusual result. These are general considerations; the registry record does not report whether either issue affected this study.

No statistical analysis plan, adjustment procedure, or imputation method is described in the registry record. The posted safety counts can be read descriptively, but the absence of analysis details limits assessment of the handling of incomplete data and multiple outcomes.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

For serious adverse events, the safety summary lists 11 participants at risk and 0 affected. For other adverse events, it lists 11 at risk and 9 affected. The registry also records 0 deaths. These figures are participant counts, not counts of individual event episodes. They describe what was recorded in the SPR001 group over 12 weeks.

The serious-event terms list contains no entries. That should be read as no serious-event terms listed in the registry summary, consistent with the reported count of 0 participants affected; it does not establish that serious events are impossible or that risk is absent. The record does not provide serious-event case details or an uncertainty interval.

The other-adverse-event count does not disclose event types, severity, duration, or the number of events experienced by each participant. The registry record also does not state whether the serious and other categories can overlap at the participant level. These summaries should therefore be interpreted as separate reported counts, not combined into a new total.

General statistical context: safety counts are most informative when the denominator, observation period, and event definitions are clear. Here, the denominator is stated as participants at risk and the timeframe is over 12 weeks. Because this was an open-label single-group study, the counts do not provide a controlled estimate of comparative safety.

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

The results describe adverse events recorded among participants receiving SPR001 at Dose A in an open-label, single-group Phase 2 study. The registry reports 0 participants with serious adverse events among 11 at risk, 9 participants with other adverse events among 11 at risk, and 0 deaths. The primary endpoint was defined over 12 weeks and included serious adverse events, dose-limiting toxicities, and adverse events leading to discontinuation of study drug.

These results do not establish that SPR001 caused every recorded event, and they do not establish that the treatment prevents or increases events relative to another option. The design has no control group, and the record identifies no randomized comparison. The counts are descriptive observations within the recorded group, not a causal comparison.

The registry lists change from baseline in 17-OHP, A4, and ACTH as secondary outcomes, but it lists no outcome analyses. The registry record therefore does not report results for those measures. The safety summary also does not report event-level detail, confidence intervals, a missing-data approach, or a statistical analysis plan. These omissions limit the precision and scope of interpretation.

General statistical context: an observed count is affected by the size of the group and the length and completeness of observation. A small study can identify events that occurred in its participants, but it may not characterize uncommon events precisely. A zero count should not be interpreted as proof of zero risk. Conversely, the count of other adverse events does not by itself show that treatment caused them or establish their clinical importance.

The appropriate statistical conclusion is limited to what the registry records: the stated numbers of participants with serious and other adverse events in this treated group during the stated period. The record does not support a comparative efficacy conclusion or a generalization beyond those observations.

13. Why This Trial Matters Statistically

This trial is statistically useful as an example of the distinction between safety description and treatment comparison. Its single-group, open-label design produces counts among participants exposed to SPR001, while offering no randomized control group against which to estimate a difference. That distinction matters because a count in a treated group and a comparative treatment effect answer different questions.

The primary endpoint is participant-based and has a defined 12-week timeframe. The registry identifies 11 participants at risk for serious and other adverse events, with 0 and 9 affected, respectively. Stating the denominator and timeframe helps readers understand the scope of those counts. The absence of event-level detail, uncertainty estimates, and registry-listed analyses also shows why a concise safety count should not be mistaken for a complete statistical account.

The record lists three biochemical secondary outcomes but no outcome analyses. This illustrates that an outcome’s presence in a registry is not the same as a posted result. Likewise, the sample-size planning assumptions described in the record do not amount to evidence that the study was designed around a particular comparative estimate: the assumptions refer to a two-arm illustration, whereas the trial itself is single group.

General statistical context: good interpretation separates observed data, design-based comparisons, and assumptions used for planning. Here, only descriptive safety counts are available for interpretation. Keeping those categories distinct helps prevent unsupported causal or precision claims and makes clear what information would be needed for stronger statistical conclusions.

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.

The principal limitation for interpretation is the absence of a control group. The study is listed as single group, open label, and not a randomized comparison. Therefore, the posted safety counts cannot be compared with a concurrent control group, and they do not establish a difference attributable to SPR001.

The enrollment is 11, and the safety summaries list 11 participants at risk. The registry record does not provide confidence intervals or other uncertainty estimates for the safety counts. It also does not report detailed event types for the other-adverse-event summary, event episodes per participant, event timing, duration, or severity. The serious-event terms list is empty, and deaths are recorded as 0.

The primary outcome is defined for participants who received at least one dose, but the record does not describe missing-data handling, completeness of follow-up, withdrawals, or whether each participant contributed the full 12-week observation period. The registry record does not report an analysis plan, multiplicity handling, or statistical tests. It lists three secondary outcomes but no outcome analyses, so no secondary outcome results can be assessed.

The sample-size assumptions are described as a planning illustration using a two-arm framework, while the actual study is single group. The study’s own sample-size justification is not reported. These limitations do not negate the descriptive counts; they define what those counts can and cannot establish. The results should be understood as recorded observations in a small exposed group, rather than as precise or comparative estimates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety and Efficacy of SPR001 in Subjects With Classic Congenital Adrenal Hyperplasia — NCT03687242.
• Registry record last updated 2025-04-01; status last verified 2025-03.
• Results first posted 2025-04-01.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03687242 is a completed Phase 2, open-label, single-group study of SPR001 at Dose A in subjects with classic congenital adrenal hyperplasia. The registry describes 12 weeks of treatment and records enrollment of 11. The primary endpoint is the incidence of treatment-emergent adverse events over 12 weeks among participants who received at least one dose.

The safety summary lists 11 participants at risk for serious adverse events, with 0 affected; for other adverse events, 11 were at risk and 9 were affected. Deaths are recorded as 0. Three secondary outcomes are listed: change from baseline in 17-OHP, A4, and ACTH. No outcome analyses are listed in the registry record.

The study has no randomized comparator. The registry record does not report a full statistical analysis plan, missing-data approach, multiplicity strategy, or the study’s sample-size justification. Interpretation is therefore limited to the descriptive safety counts and the design details recorded.