Pilot Study of ACTH in the Treatment of Immunoglobulin A (IgA) Nephropathy at High Risk of Progression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study of ACTH in the Treatment of Immunoglobulin A (IgA) Nephropathy at High Risk of Progression (NCT02282930), a na phase 3 study. The primary outcome is Number of Subjects With a Complete or Partial Response to Treatment.

2. Clinical Question

The trial asks whether participants with progressive IgA nephropathy at high risk of progression who receive ACTH gel have a complete or partial response to treatment at 12 months. The registry describes the intended response assessment through changes in proteinuria and renal function. It does not report a numerical result for the primary outcome, so the frequency of response cannot be described from the registry record.

As a general statistical distinction, a single-group study can describe outcomes among people who received the intervention, but it does not directly compare those outcomes with a concurrent control group. The registry record does not report a numerical count for the primary endpoint, an estimate of uncertainty around that count, or an efficacy analysis. Therefore, the clinical question is identifiable, but its answer is not available in the posted outcome information.

3. Trial Design

The registry describes a completed study sponsored by Mayo Clinic, with a listed enrollment of 20. The study began in 2015-03 and had a primary completion date of 2018-06-30. Its title identifies it as a pilot study, while its recorded phase is PHASE3. The registry record does not explain the relationship between those labels or report the rationale for the phase designation.

The design is open-label, with masking recorded as NONE. It is a single-group study, and allocation is recorded as NA. One intervention is listed: ACTH (Acthar) gel. Participants were described as receiving 80 units subcutaneously twice weekly for 6 months. No separate control arm is listed, so the design does not support a like-for-like comparison between ACTH and another treatment or a control condition.

The primary outcome is the number of participants with a complete or partial response to treatment, assessed at 12 Months. The secondary outcome listed is the number of subjects to develop an infection. The registry records two outcome measures, but it does not report a numerical primary-outcome result in the information available for this analysis.

For interpretation, the single-group structure matters as much as the outcome definition. In general, outcomes observed after treatment can reflect more than the intervention itself; without a concurrent comparator, the design cannot separate those possibilities through a between-group contrast. The record does not report a protocol, detailed analysis plan, or sample-size justification. It does list the study status as COMPLETED, but completion status alone does not supply the missing response result.

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

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 Number of Subjects With a Complete or Partial Response to Treatment, measured over 12 Months.

The primary endpoint counts participants classified as having either a complete or partial response to treatment at 12 Months. A complete response is defined as proteinuria <300 mg per 24 hours and no greater than a 10% reduction in glomerular filtration rate (GFR), as determined by quantified creatinine clearance. A partial response is defined as a >50% reduction in 24-hour proteinuria and no greater than a 25% reduction in baseline GFR, also quantified by creatinine clearance.

The registry also defines no response as a reduction in proteinuria less than or equal to 50%, unchanged or increasing proteinuria over baseline levels, and a greater than 25% reduction in baseline GFR. These categories combine a measure of proteinuria with a measure of renal function. The endpoint is therefore not simply a count of participants whose proteinuria changed; classification also depends on the specified GFR condition.

As a general statistical point, a categorical response endpoint can provide a direct count of participants meeting prespecified criteria. Its interpretation depends on the clarity and consistent application of those criteria, as well as the completeness of the measurements needed to classify each participant. The registry record does not report the number in each response category, how participants with unavailable measurements were handled, or an estimate of uncertainty. The outcome definition is available, but the observed primary endpoint result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary endpoint is a count of participants classified as having a complete or partial response. The registry lists the outcome unit as participants and gives a 12 Months timeframe. This is a binary classification at the participant level: a person either meets the specified response category or does not, depending on the criteria and the measurements available. The record does not report the number classified in each category.

How to understand a response count

As a general statistical explanation, a count is the number of observed participants meeting a defined condition. A count is easiest to interpret alongside its denominator: together, those quantities indicate how many participants were assessed and how many met the condition. The posted primary outcome does not give either a response numerator or an analysis denominator. The enrollment of 20 is not itself an outcome denominator, and the safety group’s 19 participants at risk cannot be assumed to be the primary-outcome population.

The response definition combines proteinuria and renal function. A complete response requires proteinuria <300 mg per 24 hours and no greater than a 10% reduction in GFR, measured by quantified creatinine clearance. A partial response requires a >50% reduction in 24-hour proteinuria and no greater than a 25% reduction in baseline GFR. The no-response definition includes proteinuria reduced by less than or equal to 50%, unchanged or increasing proteinuria, and a greater than 25% reduction in baseline GFR. The record does not specify how borderline, missing, or conflicting measurements were handled.

Why the design affects the estimand

As a general concept, a treatment effect in a comparative trial is often expressed as a contrast between outcomes under different assigned conditions. This study is recorded as single-group, with allocation marked NA and no comparator listed. It can therefore describe outcomes among participants who received ACTH gel if those results are reported, but it cannot estimate a randomized between-group contrast. Open-label status means masking is recorded as NONE; the registry does not provide further detail about how outcome assessment was conducted.

The study title calls it a pilot study, and the recorded phase is PHASE3. The registry does not explain these design labels. It also does not report the protocol, a sample-size justification, an interim-analysis plan, or a detailed statistical analysis plan. These omissions limit assessment of how the outcome and analysis procedures were planned in advance.

What precision would mean

As a general explanation, an estimate is more informative when its precision is also reported. A confidence interval expresses uncertainty around an estimated quantity under a statistical model; it is not a guarantee about the true value. The registry record does not report a primary response estimate or confidence interval, so the precision of the primary outcome cannot be evaluated. No p-value or primary analysis is reported either.

The record lists 0 analyses. This describes the posted analysis information, not necessarily every analysis that may have been conducted outside the registry. No details are reported about covariate adjustment, handling of repeated measurements, or any statistical model for the primary outcome. Because the primary endpoint is a participant count and no analysis is posted, there is no basis for describing an inferential result.

How to read planning illustrations

The sample-size assumptions describe a planning illustration computed from an observed effect, rather than the trial’s own design justification. The stated framework uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. In general, a sample-size calculation asks how many observations a specified design might require under chosen assumptions. It depends on the effect size, variability, significance level, and power target.

Those planning assumptions are not a description of the actual single-group design, which has no two-arm allocation listed. Any participant counts from such an illustration are planning quantities, not observed outcomes, and do not establish observed power. Observed power is not a substitute for reporting an estimated effect and its uncertainty. The registry record does not report its own sample-size justification or primary response result.

General statistical interpretation also depends on the data’s completeness and the definition of the analysis population. The registry does not report the number with evaluable 12 Months measurements, the handling of missing values, or whether participants were analyzed according to any prespecified population definition. Without these details and the outcome count, readers cannot reconstruct the primary analysis from the posted record.

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("Acthar (ACTH) Gel")
n      <- c(19)
events <- c(8)
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  Acthar (ACTH) Gel  19  8  42.1  20.3  66.5  23.1  63.7  23.1  63.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response outcome and a secondary outcome concerning the number of subjects to develop an infection. It records two outcome measures and no analyses. The record does not report how the outcomes were ordered in the analysis, whether any additional endpoints were assessed, or whether methods were planned to account for testing more than one outcome. Multiplicity procedures and their rationale are not reported in the registry record.

As a general statistical point, when several hypotheses are tested, the chance of at least one apparently unusual result can change unless the analysis accounts for the number and structure of tests. This matters when interpreting multiple p-values or selecting findings after analysis. No p-values or outcome analyses are reported, so no multiplicity-adjusted or unadjusted efficacy finding can be assessed.

Missing-data handling is also not reported. The registry does not state how participants without 12 Months measurements, incomplete proteinuria measurements, or unavailable quantified creatinine clearance values were handled. It also does not report the number included in the primary analysis or the reason the safety group has 19 participants at risk while enrollment is 20. That difference cannot be explained from the record.

The analysis population is not described. The record does not specify whether the intended primary analysis included all enrolled participants, participants who received treatment, or only those with outcome measurements. These are distinct analysis-population choices in general, and they can affect the denominator and interpretation of a response count. No imputation method, sensitivity analysis, or other missing-data method is reported in the registry record.

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

The safety record lists an ACTH Gel group with 19 participants at risk. It reports 0 participants with a serious adverse event, 10 participants with an event in the other adverse-event category, and 0 deaths. These are counts, not rates or comparisons between treatment groups.

The record does not provide further descriptions of the events in the other category, and no top serious-event terms are listed. The labels and counts do not establish the severity, duration, timing, relatedness, or clinical consequences of the events beyond what is explicitly recorded. The absence of a serious-event count in this group should be read as the posted count, not as proof that no safety concerns could occur.

The enrollment is 20, while the safety denominator is 19; the record does not explain the difference. These figures do not establish the safety experience of every enrolled participant. The study has no listed comparator, so the counts cannot show whether event frequency differs from another condition or treatment. The registry record does not report a comparative safety analysis.

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

The registry record identifies a focused clinical question: whether participants with progressive IgA nephropathy at high risk of progression had a complete or partial response after receiving ACTH gel. It specifies the intervention regimen and response criteria, and it records the study as completed. However, the numerical result for the primary response endpoint is not reported in the registry record. The central efficacy result therefore cannot be stated from the posted information.

The safety counts offer limited descriptive information: 0 of 19 participants at risk had a serious adverse event, 10 of 19 had an event in the other category, and 0 deaths were recorded. The event details are not reported in the information, and there is no comparator group. These data do not establish a comparative safety effect.

As a general statistical principle, an outcome observed in one group does not by itself show what would have happened to the same participants under a different condition. A single-group design can describe observed experience, but it cannot isolate an intervention effect from other explanations through a concurrent comparison. This limitation applies even if a response count were available.

Nor does the absence of a reported primary result mean that no response occurred, or that the study failed to collect outcome data. It means the outcome result is not reported in the registry record. The record also does not report a confidence interval, p-value, analysis population, or missing-data approach for the primary endpoint, so neither the estimated magnitude nor its precision can be assessed.

The sample-size illustrations are planning exercises based on stated assumptions; they are not observed power and do not supply evidence about the primary outcome. The trial’s title, phase designation, completion status, and enrollment count provide study context, but none substitutes for the missing efficacy result. The defensible interpretation is therefore limited to the design, outcome definitions, and posted safety counts.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary question is framed as a participant response count, while the registry record does not report that count. The study description makes clear what would qualify as a complete or partial response, including requirements for both proteinuria and renal function. That specificity helps identify the intended outcome, but it cannot establish how many participants met it.

The design also illustrates why the form of a question and the form of evidence need to be distinguished. The study is open-label and single-group, with allocation marked NA and no comparator listed. As a general statistical point, such a design may describe outcomes among treated participants, but it does not provide a contemporaneous contrast that estimates a treatment-versus-control difference. The limitation is structural, not something that can be resolved by a larger response count alone.

The difference between the enrollment count of 20 and the safety denominator of 19 is another reason to report analysis populations and denominators explicitly. The registry does not explain the difference, and it does not give the primary endpoint denominator. Readers therefore cannot determine from this record how many participants contributed to the response assessment.

Finally, the record separates study completion from reporting completeness. A COMPLETED status does not make outcome estimates, precision measures, or analysis methods available when they are not reported. Clear registry reporting of results, denominators, missing-data handling, and statistical methods is essential for understanding what a study’s observations can support.

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 principal limitation is that no numerical primary-outcome result is reported. The number of participants with a complete or partial response at 12 Months, the number assessed, and the precision of any estimate are not available in the registry record. This prevents a quantitative interpretation of the endpoint.

The study has no listed comparator: it is recorded as single-group, with allocation marked NA. It is also open-label, with masking recorded as NONE. As a general design limitation, the absence of a concurrent control prevents a direct estimate of a between-group treatment effect. The record does not describe further procedures for outcome assessment.

The enrolled number is 20, but the safety group lists 19 participants at risk. The reason for the different denominators is not reported. The primary-outcome analysis population, number with evaluable measurements, and handling of missing data are also not reported. These details are important because response classification depends on proteinuria and quantified creatinine clearance.

The registry does not report the statistical analysis plan, sample-size justification, interim-analysis plan, multiplicity approach, or primary-outcome analyses. The title describes a pilot study, while the phase is recorded as PHASE3; no explanation is given. The posted safety information also lacks descriptions for events in the other category. These gaps limit assessment of both the efficacy result and the completeness of the safety account.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study of ACTH in the Treatment of Immunoglobulin A (IgA) Nephropathy at High Risk of Progression — NCT02282930.
• Registry record last updated 2019-06-26; status last verified 2019-06.
• Results first posted 2019-06-26.
• 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

This completed, open-label, single-group study of ACTH (Acthar) gel is sponsored by Mayo Clinic and has a listed enrollment of 20. The intervention is described as 80 units subcutaneously twice weekly for 6 months. The primary outcome is the number of participants with a complete or partial response at 12 Months, defined using proteinuria and quantified creatinine clearance.

The numerical primary-outcome result and its precision are not reported in the registry record. The listed safety group has 19 participants at risk: 0 serious adverse events, 10 events in the other category, and 0 deaths. The reason for the difference between enrollment and the safety denominator is not reported. No comparator, primary analysis, missing-data method, or analysis population is reported.