This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate RIST4721 in Hidradenitis Suppurativa (HS) (NCT05348681), a randomized phase 2 study. The primary outcome is Incidence of TEAEs.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05348681 |
| Phase | Phase 2 |
| Condition | Hidradenitis Suppurativa |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 25 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Aristea Therapeutics, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled participants with hidradenitis suppurativa. The registry reports enrollment of 25. It does not report further participant characteristics in the record summarized for these results, so the population cannot be described more narrowly from the posted information.
Intervention
Participants assigned to RIST4721 received 400 mg as four active 100 mg tablets once daily for 12 weeks. The trial was randomized, double-blinded, placebo-controlled, and parallel-group.
Comparator
The comparator was placebo, given as four placebo tablets once daily for 12 weeks. The RIST4721 arm included 17 participants and the placebo arm included 8, as reported in the outcome results.
Primary question
The primary endpoint counted participants with at least one treatment-emergent adverse event (TEAE), from baseline to Week 12 or the end of study participation. This is a safety outcome, not a measure of improvement in hidradenitis suppurativa. A comparative treatment-effect estimate for this binary endpoint is not reported in the registry record.
The registry also lists the proportion achieving HiSCR50 at Week 12 as a secondary outcome. Results for that outcome are not reported in the registry record. Thus, the posted information describes the planned comparison and some safety counts, but does not establish a comparative efficacy result.
3. Trial Design
This was a randomized, double-blinded, placebo-controlled, parallel-group phase 2a study of RIST4721 in participants with hidradenitis suppurativa. The sponsor was Aristea Therapeutics, Inc. The registry records a start date of 2022-07-18, primary completion on 2023-02-28, enrollment of 25, and a status of terminated. The reason for termination is not reported in the registry record.
The two treatment arms were RIST4721 400 mg and placebo. The RIST4721 regimen was four active 100 mg tablets once daily for 12 weeks; the placebo regimen was four placebo tablets once daily for 12 weeks. The recorded primary endpoint concerns TEAEs from baseline to Week 12 or the end of study participation. The study is described as double-blinded, but further details about who was masked or how masking was maintained are not reported in the registry record.
Randomization is intended, in general, to reduce systematic differences between treatment groups at assignment. Double-blinding is generally intended to limit the influence of treatment knowledge on participant experience, clinical care, and outcome assessment. Those general purposes do not establish that groups were balanced in this study or that masking was successful; details to evaluate either point are not reported in the registry record.
The outcome results list 17 participants in the RIST4721 arm and 8 in the placebo arm. These arm sizes are not equal. The registry record does not report the randomization ratio or explain the distribution of participants across the arms. The primary completion date and terminated status do not, by themselves, explain why the study ended or whether the planned study procedures were completed. Such reasons are not reported in the registry record.
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
| Stage | RIST4721 400 mg | Placebo |
|---|---|---|
| STARTED | 17 | 8 |
| COMPLETED | 4 | 2 |
| NOT COMPLETED | 13 | 6 |
Reasons for not completing this period:
| Reason | RIST4721 400 mg | Placebo |
|---|---|---|
| Study terminated by Sponsor | 8 | 3 |
| Withdrawal by Subject | 1 | 1 |
| Lost to Follow-up | 1 | 1 |
| Adverse Event | 1 | 0 |
| Other | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: Subjects with at least one TEAE
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.
| Characteristic | Unit | RIST4721 400 mg | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 17 | 8 | 25 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 17 | 8 | 25 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 15 | 7 | 22 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 2 | 5 |
| Race (NIH/OMB): White | Participants | 14 | 5 | 19 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: Canada | participants | 3 | 1 | 4 |
| Region of Enrollment: United States | participants | 14 | 7 | 21 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of TEAEs, measured over Baseline to Week 12 (or end of study participation).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the incidence of TEAEs, expressed as the count of participants with at least one TEAE. The stated population is subjects with at least one TEAE, and the timeframe is baseline to Week 12 or the end of study participation. The posted results report 9 participants in the RIST4721 arm and 4 in the placebo arm with this endpoint. The arm sizes are 17 and 8, respectively.
A TEAE is an adverse event that emerges or is recorded during treatment. In general, counting participants with at least one event is a way to describe how many people experienced any event within the specified observation period. It treats a participant with multiple events the same as a participant with one event for this particular count; it does not describe how many events occurred in total, their duration, or their severity. Those other details are not conveyed by this endpoint alone.
Safety endpoints are used to characterize events occurring during a study and to help describe the observed safety experience in each arm. A participant count is readily interpretable, but a count alone does not quantify the precision of a comparison between groups. The registry record does not report a comparative estimate, confidence interval, or analysis for this endpoint. The count should therefore be read as a descriptive result, not as a conclusion about a treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary-endpoint counts are 9 participants with at least one TEAE among 17 in the RIST4721 arm and 4 among 8 in the placebo arm. These are descriptive arm-specific counts. They do not, by themselves, establish whether the underlying event experience differs between treatment groups. No comparative binary-endpoint estimate is reported in the registry record; the record indicates that values for a two-arm comparison were missing or not estimable. A p-value and confidence interval for this comparison are not reported in the registry record.
In general, an unadjusted comparison of event proportions uses the event counts together with the numbers observed in each group. The resulting estimate describes a contrast between groups, while a confidence interval describes the uncertainty around that estimate under the assumptions of the method. Neither can be inferred just by reading the counts as if they were percentages. No new comparison should be calculated from the posted summaries when the registry record does not give an estimable result.
The arms have different reported sizes, and the number of participants is limited. In general, estimates from relatively small groups can be imprecise, particularly when events are uncommon. The record does not provide a confidence interval or another precision measure for the primary endpoint, so the range of values compatible with the observed data cannot be assessed from the posted result. The absence of a comparative estimate is not evidence that the groups are equivalent, nor does it establish a direction or size of any difference.
The primary endpoint is a safety count, not the secondary efficacy outcome. The registry lists the proportion achieving HiSCR50 at Week 12 as a secondary outcome, but its results are not reported in the registry record. Consequently, these posted TEAE counts do not answer whether participants experienced a clinical response, and they cannot be used as a substitute for that outcome.
The registry records the trial as terminated, but the reason for termination is not reported in the registry record. The status alone cannot establish whether termination was related to safety, efficacy, recruitment, operational considerations, or another cause. Likewise, the record does not state whether the observed enrollment or outcome data were affected by the termination.
The most defensible reading is therefore limited: the registry reports the number of participants with at least one TEAE in each arm over the stated observation period, along with selected serious-event information. It does not report a formal comparison for the primary endpoint or results for the listed secondary efficacy outcome. Any interpretation beyond those observations would require information not reported in the registry record.
9. Statistical Methods Explained
The primary outcome is binary at the participant level: a participant either had at least one TEAE during the stated period or did not. The registry reports counts of participants with an event and the number of participants in each arm. These counts describe the observed safety experience, but a formal comparison requires an estimand and an analysis method. The registry record does not report an analysis for the two-arm binary comparison; it notes that values were missing or not estimable.
What does a binary comparison estimate?
In general, a binary comparison summarizes how the event occurrence differs between groups. Common choices include a difference between event proportions, a ratio of proportions, or an odds-based measure. Each has a distinct interpretation and can yield a different numerical summary. The registry record does not specify or report a comparative measure for the TEAE endpoint, so none should be attributed to this study from the posted counts alone. A comparison also needs an uncertainty measure, usually a confidence interval, to communicate how much precision the data support. Such an interval is not reported in the registry record.
Why do event counts need denominators?
A count alone depends on how many people were observed. In general, the denominator makes it possible to interpret an event count in relation to the group at risk or included in the analysis. The posted outcome lists the arm sizes as 17 for RIST4721 and 8 for placebo, with event counts of 9 and 4. These are reported separately; no additional percentage or contrast is calculated. The registry record does not clarify whether the endpoint denominators represent all randomized participants, treated participants, or another analysis population. That definition is not reported in the registry record.
What does a confidence interval add?
In general, a confidence interval gives a range of estimates that are reasonably compatible with the observed data under a specified statistical method and its assumptions. It is not a guarantee that the true value lies in a particular interval, and its width reflects both the amount of information and the method used. Because no comparative estimate or confidence interval is reported for the primary endpoint, the precision of a treatment-group contrast cannot be evaluated from the posted results. A small observed count or an apparently similar count does not, on its own, demonstrate that the groups are alike.
Why does analysis choice matter?
For binary outcomes, methods can behave differently when group sizes are small or event counts are sparse. In general, some large-sample approximations may be less reliable when the data contain few events; alternative exact or model-based approaches may be considered depending on the question and the analysis plan. This general issue does not identify which method was used for this trial. The statistical analysis plan, any adjustment variables, and the method intended for the primary comparison are not reported in the registry record.
Randomization supports a comparative design, but it does not remove the need to specify the analysis population, handling of missing outcome data, and treatment of participants who do not follow the assigned regimen. In general, these choices affect the interpretation of an estimated treatment effect. The registry record does not report the analysis population for the posted primary endpoint, the handling of missing data, or the approach to protocol deviations. No assumption about an intention-to-treat or per-protocol analysis can therefore be made.
How should planning illustrations be read?
In general, sample-size calculations are planning tools: they relate a target effect, a statistical threshold, an allocation scheme, and assumptions about the outcome to a planned amount of information. They are not estimates of what the trial observed and are not measures of observed power. The planning assumptions recorded for the illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Those assumptions describe planning illustrations, not necessarily the trial's design or analysis. The registry record does not report the trial's own sample-size justification, so the illustrations should not be treated as the basis for enrollment or as evidence that the study could detect a particular effect.
Equal allocation in a planning illustration is an assumption for that calculation. It should not be confused with the reported outcome arm sizes, which are 17 for RIST4721 and 8 for placebo. A planning calculation based on a fraction of an observed effect is also conditional on that observed effect and is not independent confirmation of it. Any interpretation of such illustrations must remain separate from the trial's posted outcome evidence.
Finally, a statistical result addresses a defined endpoint under a specified analysis. The primary endpoint is a count of participants experiencing at least one TEAE during the stated timeframe. It does not measure event burden, clinical response, or the overall balance of benefits and harms. Those questions require additional outcomes and appropriate analyses; results or methods for them are not reported in the registry record beyond the listed secondary outcome.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| RIST4721 400 mg | 17 | 9 | 52.9% | 27.8% to 77.0% | 31.0% to 73.8% | 30.8% to 74.0% |
| Placebo | 8 | 4 | 50.0% | 15.7% to 84.3% | 21.5% to 78.5% | 21.2% to 78.8% |
R code and output
arm <- c("RIST4721 400 mg", "Placebo")
n <- c(17, 8)
events <- c(9, 4)
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 RIST4721 400 mg 17 9 52.9 27.8 77.0 31.0 73.8 30.8 74.0
ARM Placebo 8 4 50.0 15.7 84.3 21.5 78.5 21.2 78.811. Multiplicity, Missing Data and Analysis Populations
The registry lists one secondary outcome: the proportion of participants achieving HiSCR50 at Week 12. It also reports 3 outcome measures overall. Results for the listed secondary outcome are not reported in the registry record, and no analyses are posted. The registry record does not explain how the outcome measures relate to one another or identify which were designated primary or secondary beyond the stated primary endpoint and the listed secondary outcome.
When a study evaluates multiple outcomes, time points, or treatment comparisons, the chance of at least one apparently notable result can increase. In general, multiplicity procedures may control that risk or define a hierarchy for interpretation. Whether such procedures were planned or used in this trial is not reported in the registry record. No multiplicity adjustment or testing hierarchy can be inferred from the outcome listings.
Missing outcome data can also affect interpretation. In general, results may depend on why data are missing and how the analysis handles participants without an observed endpoint. The registry record does not report the amount or pattern of missing data, any imputation method, or a sensitivity analysis. The note that a two-arm binary comparison was not estimable does not establish why it was not estimable, nor does it describe participant-level missingness.
The analysis population for the primary endpoint is not reported in the registry record. It is therefore unclear whether the posted arm denominators correspond to all randomized participants, treated participants, or a defined subset. The record also does not report a statistical analysis plan, protocol-deviation rules, or any interim-analysis plan. These omissions limit assessment of how the posted counts were selected and whether the analysis followed a prespecified approach.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| RIST4721 400 mg | 1 | 17 | 5.9% |
| Placebo | 1 | 8 | 12.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| RIST4721 400 mg | 0 of 17 |
| Placebo | 0 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| RIST4721 400 mg | 9 of 17 |
| Placebo | 4 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | RIST4721 400 mg | Placebo |
|---|---|---|---|
| Migraine | Nervous system disorders | 1 of 17 | 0 of 8 |
| Obstructive pancreatitis | Gastrointestinal disorders | 0 of 17 | 1 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | RIST4721 400 mg | Placebo |
|---|---|---|---|
| COVID-19 | Infections and infestations | 2 of 17 | 1 of 8 |
| Urine odour abnormal | Renal and urinary disorders | 3 of 17 | 0 of 8 |
| Nasopharyngitis | Infections and infestations | 0 of 17 | 2 of 8 |
| Liver function test increased | Investigations | 2 of 17 | 0 of 8 |
| Sciatica | Nervous system disorders | 1 of 17 | 1 of 8 |
| Abdominal pain lower | Gastrointestinal disorders | 1 of 17 | 0 of 8 |
| Diarrhoea | Gastrointestinal disorders | 0 of 17 | 1 of 8 |
| Fatigue | General disorders | 1 of 17 | 0 of 8 |
| Chest pain | General disorders | 0 of 17 | 1 of 8 |
| Chlamydial infection | Infections and infestations | 1 of 17 | 0 of 8 |
Serious events with the highest arm-level rate: obstructive pancreatitis (12.5%), migraine (5.9%).
The registry reports one participant with a serious adverse event in the RIST4721 arm and one in the placebo arm. It reports zero deaths in each arm. These are participant counts, not a complete description of the nature, duration, severity, or outcome of every event. The registry also reports 9 participants with other adverse events among 17 in the RIST4721 arm and 4 among 8 in the placebo arm. These other-event figures should not be confused with the serious-event counts or treated as event totals.
The serious-event term entries include Obstructive pancreatitis, listed as 12.5%, and Migraine, listed as 5.9%. The registry information summarized for these results does not specify the arm attribution for these term entries, so they should not be assigned to a treatment group. Their percentages should be read as reported and not as a basis for deriving additional counts.
In general, serious adverse events and other adverse events are distinct safety summaries, and a participant can contribute to more than one category depending on the event definitions and reporting rules. The registry record does not provide enough detail to reconstruct event histories or determine whether particular categories overlap. The counts describe what was reported; they do not establish a comparative safety effect, especially without an analysis and precision estimates.
13. What the Result Does, and Does Not, Mean
The posted results establish that the registry records 9 participants with at least one TEAE in the RIST4721 arm and 4 in the placebo arm, with arm sizes of 17 and 8. It also records one participant with a serious adverse event in each arm and zero deaths in each arm. These are descriptions of the reported participants and events during the recorded study period.
They do not establish that RIST4721 caused or prevented any particular event, or that the safety experience was the same or different between arms. In general, observed counts in a randomized study can inform a comparison, but the comparison requires a defined analysis and an assessment of uncertainty. The registry record does not report an estimable two-arm comparison for the primary binary endpoint, nor a confidence interval or p-value. The counts alone cannot show the precision of a difference or rule out meaningful variation.
The results also do not answer the efficacy question. The registry lists achievement of HiSCR50 at Week 12 as a secondary outcome, but does not report its results. No conclusion about clinical response can be drawn from the TEAE endpoint, because it measures a safety event rather than change in hidradenitis suppurativa.
More broadly, the record does not report the analysis population, missing-data procedures, or the reason the trial was terminated. These details matter when judging how completely the posted counts represent the randomized groups and how the study ended. Their absence does not justify assuming either that all participants completed follow-up or that termination reflected a particular result.
The narrow conclusion is that the registry reports arm-specific safety counts, but does not provide a formal comparative result for the primary endpoint or a posted result for the listed secondary efficacy outcome. The evidence in this record is therefore descriptive and incomplete for judging comparative effects.
14. Why This Trial Matters Statistically
This trial illustrates why an outcome count and a treatment comparison are not interchangeable. The registry reports counts of participants with at least one TEAE in each randomized arm, but the two-arm comparison is not reported as estimable. Without a comparative estimate and a measure of uncertainty, the counts cannot answer how large or precise a group contrast may be. This distinction is central to reading registry results responsibly.
The record also separates safety from efficacy. The primary outcome is a safety endpoint, while HiSCR50 at Week 12 is listed as a secondary outcome. Because the secondary result is not reported in the registry record, the available safety counts should not be interpreted as evidence about clinical response. Clear separation of outcome questions helps prevent one type of result from being used to imply another.
The study's terminated status and relatively small arm sizes make careful reporting especially important, but they do not explain what happened. The reason for termination, analysis populations, missing-data approach, and statistical analysis plan are not reported in the registry record. Those details would help readers understand the completeness and context of the results without changing what the reported counts themselves say.
Finally, the planning assumptions are distinct from the observed evidence. In general, planning illustrations depend on assumptions about the effect to detect and the analysis; they are not observed power and do not demonstrate that a study had a particular ability to detect an effect. This record is a useful example of why registry status, outcome definitions, observed counts, comparative analyses, and planning calculations must be interpreted as separate kinds of information.
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 posted results are limited to descriptive counts for the primary safety endpoint and selected adverse-event information. The registry record does not report an estimable two-arm comparison for the binary endpoint, a confidence interval, or a p-value. As a result, comparative magnitude and precision cannot be assessed from these results.
The arm sizes are 17 for RIST4721 and 8 for placebo. The record does not report the analysis population or explain whether these denominators include all randomized participants, all treated participants, or a different set. It also does not report the amount or pattern of missing data, how missing outcomes were handled, or whether sensitivity analyses were performed. These gaps limit assessment of how the posted endpoint counts relate to the planned study population.
The registry identifies HiSCR50 at Week 12 as a secondary outcome but does not report its result. The record lists 3 outcome measures overall, while analyses are not posted. It does not report how multiplicity was addressed, whether any interim analyses occurred, or the statistical analysis plan. The reason for the terminated status is not reported in the registry record, and the status alone cannot explain the available results.
Further limitations include the absence of reported participant characteristics beyond the condition and outcome arm sizes, and the lack of detail on serious-event term attribution. The record does not describe event duration, severity grading, or the method used to assess events. These limitations are specific to what is reported for this trial and constrain interpretation; they do not establish that the underlying study documents lack those details.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study to Evaluate RIST4721 in Hidradenitis Suppurativa (HS) — NCT05348681.
- Registry record last updated 2023-06-13; status last verified 2023-05.
- Results first posted 2023-06-13.
- 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.
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19. Record Summary
The registry record describes a randomized, double-blinded, placebo-controlled, parallel-group phase 2a study of RIST4721 in hidradenitis suppurativa. It records enrollment of 25, a start date of 2022-07-18, primary completion on 2023-02-28, and terminated status. Participants in the active arm received RIST4721 400 mg as four active 100 mg tablets once daily for 12 weeks; the placebo arm received four placebo tablets once daily for 12 weeks.
The primary endpoint was the number of participants with at least one TEAE from baseline to Week 12 or the end of study participation. The posted counts were 9 of 17 for RIST4721 and 4 of 8 for placebo. One participant with a serious adverse event and zero deaths were reported in each arm. The registry lists HiSCR50 at Week 12 as a secondary outcome, but its result is not reported in the registry record. A comparative estimate for the primary endpoint, analysis details, and the reason for termination are also not reported in the registry record.