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 Acthar Gel for Active Systemic Lupus Erythematosus (SLE) (NCT02953821), a randomized phase 4 study. The primary outcome is Physician's Global Assessment (PGA).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02953821 |
| Phase | Phase 4 |
| Condition | Lupus Erythematosus, Systemic |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 172 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mallinckrodt |
| Results posted | Yes |
2. Clinical Question
Population
Participants with persistently active systemic lupus erythematosus despite moderate dose corticosteroids, as described in the official trial title. The primary outcome population is the mITT population with a score at the given week. The registry record does not provide further eligibility details in the information.
Intervention
Acthar Gel, administered every other day for 4 weeks and then twice per week for 20 weeks. The trial description states that participants received their assigned treatment for 24 weeks.
Comparator
Placebo Gel, described as looking like Acthar Gel but containing no medicine. It followed the same schedule: every other day for 4 weeks and then twice per week for 20 weeks.
Primary question
How did the Physician's Global Assessment (PGA) score compare across treatment groups at the reported assessment times? PGA is a 100 mm visual analogue scale, with higher scores indicating more severe disease activity and lower scores indicating improvement. Numerical outcome estimates and a treatment-group comparison are not reported in the registry record.
The study was designed to assess efficacy and safety in active systemic lupus erythematosus. The primary outcome description lists Baseline, Week 16, and Week 24 as time points. Secondary outcomes listed in the registry include severe flare based on the SELENA Flare Index at Week 16, cutaneous disease activity, swollen or tender joints, and prednisone dose reduction at Week 20 and Week 24. These listed outcomes describe what the trial planned to assess; their numerical results are not reported in the registry record.
3. Trial Design
This was a Phase 4, randomized, double-blind, parallel-group, placebo-controlled study sponsored by Mallinckrodt. The registry lists enrollment of 172 participants. It describes two groups: Acthar Gel and Placebo Gel. The brief description says the doctor assigns participants to a group in a manner like flipping a coin, while the registry identifies allocation as randomized. The record does not report details of sequence generation or allocation concealment.
Both groups followed the same treatment schedule over 24 weeks. Participants received the assigned gel every other day for 4 weeks, followed by twice-per-week dosing for 20 weeks. The placebo was described as looking like Acthar Gel but containing no medicine. The study is identified as double masked; the registry information does not specify which roles, beyond the general description of the doctor or staff, were masked.
The registry gives the trial start as 2016-12-16, primary completion as 2019-07-31, and status as completed. Its primary outcome is the mean Physician's Global Assessment score, with observations listed at Baseline, Week 16, and Week 24. The primary outcome population is described as the mITT population with a score at the given week. The record does not provide a numerical comparison of PGA between groups.
Several secondary outcomes are named, including severe flare, skin disease activity, joint counts, and prednisone dose reduction. Their presence in the registry does not establish that results were reported for them. Numerical results for these secondary outcomes are not reported in the registry record. Details such as the planned sample-size justification, interim analyses, and the full statistical analysis plan are also 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.
Before assignment: Of 293 who signed informed consent, 172 were randomized into treatment groups
Overall Study
| Stage | Placebo Gel | Acthar Gel |
|---|---|---|
| STARTED | 86 | 86 |
| Safety Population | 86 | 86 |
| Modified Intent to Treat (mITT) Populati | 85 | 84 |
| Per Protocol (PP) Population | 72 | 75 |
| Completed Week 16 Visit | 76 | 77 |
| Completed Study Treatment (Week 24) | 73 | 76 |
| COMPLETED | 71 | 73 |
| NOT COMPLETED | 15 | 13 |
Reasons for not completing this period:
| Reason | Placebo Gel | Acthar Gel |
|---|---|---|
| Adverse Event | 0 | 4 |
| Death | 1 | 0 |
| Progressive Disease | 5 | 1 |
| Lost to Follow-up | 2 | 0 |
| Physician Decision | 1 | 1 |
| Withdrawal by Subject | 3 | 3 |
| Change of address | 0 | 1 |
| Lack of Efficacy | 1 | 0 |
| Out of state for indeterminate time | 0 | 1 |
| No improvement | 0 | 1 |
| Refused follow-up visit | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: mITT population with score at the given week
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: Safety Population (except for study-specific measures)
| Characteristic | Unit | Placebo Gel | Acthar Gel | Total |
|---|---|---|---|---|
| Participants analysed | 86 | 86 | 172 | |
| Age, Continuous | years | 39.3 (SD 12.99) | 40.1 (SD 12.45) | 39.7 (SD 12.69) |
| Sex: Female, Male: Female | Participants | 82 | 76 | 158 |
| Sex: Female, Male: Male | Participants | 4 | 10 | 14 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 19 | 19 | 38 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 8 | 9 | 17 |
| Race (NIH/OMB): White | Participants | 30 | 33 | 63 |
| Race (NIH/OMB): More than one race | Participants | 29 | 25 | 54 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Physician's Global Assessment (PGA), measured over Baseline, Week 16, Week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the Physician's Global Assessment (PGA), summarized as a mean of a continuous measure. The registry describes PGA as a 100 mm visual analogue scale. Higher scores indicate more severe disease activity, while lower scores indicate improvement. The stated assessment times are Baseline, Week 16, and Week 24, and the defined population is the mITT population with a score at the given week.
A clinician global assessment can provide a broad assessment of disease activity rather than focusing on one symptom or organ measure. As a general statistical concept, a continuous scale can retain gradations in the measured score, and the mean describes the average score in a group. That summary does not describe every participant's experience or the spread of individual scores; the registry identifies standard deviation as the dispersion measure.
Interpretation depends on the numerical values, their variability, and a clearly specified comparison between groups or over time. Those estimates and a statistical test or confidence interval for PGA are not reported in the registry record. The direction assigned to the scale is clear, but without the outcome values it is not possible to describe the observed size or precision of any change in this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial question and the primary outcome definition, but it does not report numerical PGA results. It identifies the mean PGA score, standard deviation, the mITT population with a score at the relevant week, and assessments at Baseline, Week 16, and Week 24. It does not provide group means, standard deviations, changes from Baseline, between-group estimates, confidence intervals, or p-values. As a result, the record does not allow a reader to quantify a treatment contrast or its precision for the primary outcome.
The score's direction can still be interpreted from its definition: higher PGA values indicate more severe disease activity, and lower values indicate improvement. This direction does not itself show what happened in either group. The scale description alone cannot establish whether scores changed, whether groups differed, or whether any observed difference was small or large. Those conclusions require outcome estimates, which are not reported in the registry record.
The registry lists secondary measures, including severe flare based on the SELENA Flare Index at Week 16, CLASI total activity score, the mean number of swollen or tender joints on the 28-joint count, and participants with a prednisone dose decrease to < 7.5 mg/day at Week 20 and Week 24. No numerical results for these outcomes are reported in the registry record. The listed outcome names therefore identify what was to be assessed, not the results of those assessments.
The safety information includes group counts for serious adverse events, other adverse events, and deaths. These are descriptive counts in the registry record. They do not, on their own, provide a complete comparison of risks: information about event definitions, timing, participant-level overlap, and statistical uncertainty is not reported. The listed serious-event terms and percentages also do not provide the full clinical context for each event.
In general, a confidence interval communicates the range of values compatible with an estimate under the statistical model and helps convey precision. No such interval for the primary treatment comparison is reported in the registry record. General cautions about interpreting trial estimates therefore apply, but there is no reported primary estimate to interpret. The record supports a description of the design, outcome definitions, and selected safety counts, not a conclusion about the size or direction of an efficacy effect.
9. Statistical Methods Explained
What does the primary summary measure?
The primary outcome is a continuous score reported as a mean, with standard deviation identified as its dispersion measure. In general, the mean describes the average observed value in a group, while the standard deviation describes how spread out individual values are around that average. These summaries answer different questions: an average does not show how similar or variable participants' scores were.
The registry defines PGA as a 100 mm visual analogue scale and gives the direction of interpretation: higher scores correspond to more severe disease activity; lower scores indicate improvement. The time frame is Baseline, Week 16, and Week 24. The outcome population is the mITT population with a score at the given week. The registry does not report the values at those times or explain how any missing score would be handled.
What would a treatment contrast represent?
In general, a treatment contrast compares outcomes between groups, or compares change from Baseline between groups, depending on the prespecified analysis. A mean alone in one group would not establish a comparative effect. Interpretation also depends on which time point or contrast was designated as primary, how baseline values were used, and whether the analysis adjusted for other factors. Those details are not reported in the registry record. The record does not provide a numerical contrast, confidence interval, or p-value for PGA.
In general, a confidence interval gives a range of estimates compatible with the observed data and statistical model. A narrower interval indicates greater precision than a wider interval, but neither width nor position can be assessed without the actual estimate and interval. A p-value addresses compatibility with a specified null hypothesis under model assumptions; it does not convey the size or clinical importance of an effect. No primary-outcome p-value or interval is reported in the registry record.
What do randomization and masking contribute?
Randomized allocation is intended, in general, to make treatment-group assignment independent of participants' measured and unmeasured characteristics at the time of assignment. This can support a fair comparison, though it does not guarantee identical groups in a particular trial. The registry identifies allocation as randomized and the study as double masked. The record does not report the randomization method, concealment procedures, or which study roles were masked.
Masking is intended, in general, to reduce the influence of treatment knowledge on care, reporting, and outcome assessment. A placebo that looks like the active gel can help maintain masking, as described in the trial summary. The registry record does not report whether masking was assessed or maintained throughout participation. These design features describe safeguards; they do not replace the need for reported outcome estimates and analysis details.
What is the role of the planning assumptions?
The registry information describes a planning illustration based on a stated fraction of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It distinguishes participants per arm for outcomes other than time-to-event outcomes; time-to-event illustrations are described in terms of total events. These are planning assumptions, not observed trial findings and not observed power. The actual numerical illustrations are not reported in the registry record. The trial's own sample-size justification is not reported in the registry record, so the illustration should not be treated as evidence of the trial's original design rationale.
As a general concept, a sample-size calculation estimates how much information a design may need under chosen assumptions about an effect, variability, significance level, and allocation. The calculation depends on those assumptions. An illustration based on an observed effect is retrospective and should not be described as the probability that the completed study detected a true effect. No conclusion about the planning assumptions' accuracy can be drawn without the actual estimates and the trial's design documentation.
Why can variability matter?
In general, variability affects the precision of estimated means and group contrasts: more spread in the measured scores can make an estimate less precise for a given amount of information. Standard deviation is the registry-listed dispersion measure for the continuous primary outcome. The numerical standard deviations are not reported in the registry record. Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes; it can undermine standard errors and confidence intervals if not addressed. The record does not report whether over-dispersion was assessed or whether a particular model was used.
The primary outcome is continuous, but that fact alone does not reveal which statistical test or model was used. The registry record does not report the method for handling repeated assessments, baseline adjustment, missing values, or departures from model assumptions. These methods should not be inferred from the endpoint description or from the trial's randomized design.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies one primary outcome but lists multiple assessment times: Baseline, Week 16, and Week 24. It also names several secondary outcomes, some with more than one assessment time. When many outcomes, time points, or contrasts are tested, the chance of obtaining at least one apparently notable result can increase. As a general statistical principle, multiplicity procedures can control that risk, but the appropriate approach depends on which comparisons were planned and how they were prioritized.
The registry record does not report the multiplicity strategy, the testing hierarchy, or which specific contrast was designated for the primary analysis. It also does not report any inferential analyses for the primary or secondary outcomes. Therefore, the listed outcomes and time points cannot be used to infer what testing adjustments were planned or whether an outcome met a prespecified criterion.
The primary population is described as the mITT population with a score at the given week. The registry does not define the membership of that population beyond this wording. It does not report the number of participants contributing scores at each assessment, reasons for missing measurements, or methods used to address missing data. In general, missing outcomes can affect both the amount of information available and the interpretation of an analysis, particularly when the chance of missingness is related to health status or treatment experience.
The record does not report whether analyses followed intention-to-treat principles, whether participants were excluded after randomization, or what sensitivity analyses were conducted. These details are not reported in the registry record. Without them, the reader cannot assess how the analysis population and missing measurements may have influenced the outcome estimates. No analysis method should be inferred from the trial design alone.
11. 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 |
|---|---|---|---|
| Placebo Gel | 8 | 86 | 9.3% |
| Acthar Gel | 4 | 86 | 4.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo Gel | 1 of 86 |
| Acthar Gel | 0 of 86 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo Gel | 23 of 86 |
| Acthar Gel | 31 of 86 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo Gel | Acthar Gel |
|---|---|---|---|
| Systemic lupus erythematosus | Musculoskeletal and connective tissue disorders | 1 of 86 | 2 of 86 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 86 | 0 of 86 |
| Appendicitis | Infections and infestations | 1 of 86 | 0 of 86 |
| Gastroenteritis | Infections and infestations | 1 of 86 | 0 of 86 |
| Herpes zoster | Infections and infestations | 0 of 86 | 1 of 86 |
| Peritonitis | Infections and infestations | 1 of 86 | 0 of 86 |
| Pneumonia | Infections and infestations | 1 of 86 | 0 of 86 |
| Pyelonephritis | Infections and infestations | 1 of 86 | 0 of 86 |
| Soft tissue infection | Infections and infestations | 1 of 86 | 0 of 86 |
| Drug abuse | Psychiatric disorders | 1 of 86 | 0 of 86 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo Gel | Acthar Gel |
|---|---|---|---|
| Urinary tract infection | Infections and infestations | 10 of 86 | 6 of 86 |
| Headache | Nervous system disorders | 5 of 86 | 6 of 86 |
| Insomnia | Psychiatric disorders | 4 of 86 | 7 of 86 |
| Upper respiratory tract infection | Infections and infestations | 1 of 86 | 9 of 86 |
| Nasopharyngitis | Infections and infestations | 6 of 86 | 3 of 86 |
| Hypertension | Vascular disorders | 0 of 86 | 6 of 86 |
Serious events with the highest arm-level rate: systemic lupus erythematosus (2.3%), thrombocytopenia (1.2%), appendicitis (1.2%), gastroenteritis (1.2%), herpes zoster (1.2%).
The registry reports serious adverse events for 86 participants at risk in each group: 8 participants affected in the Placebo Gel group and 4 in the Acthar Gel group. It reports other adverse events for 86 participants at risk in each group: 23 participants affected in the Placebo Gel group and 31 in the Acthar Gel group. The death counts are 1 for Placebo Gel and 0 for Acthar Gel. These are the reported counts, not adjusted comparisons.
In general, adverse-event counts describe participants recorded as affected, but the interpretation depends on definitions, follow-up, event timing, and whether participants could have more than one event. The registry information does not report those details or statistical uncertainty around the group counts. It also does not establish whether the observed differences arose from treatment or other causes. The counts should be read descriptively rather than as proof of a causal safety difference.
The record lists serious-event terms with percentages: Systemic lupus erythematosus, 2.3%; Thrombocytopenia, 1.2%; Appendicitis, 1.2%; Gastroenteritis, 1.2%; Herpes zoster, 1.2%; and Peritonitis, 1.2%. The registry information does not give further context for these terms in the listed summary. The percentages should not be assigned to a treatment group unless the registry record explicitly does so.
12. What the Result Does, and Does Not, Mean
The trial record describes a randomized, double-blind, parallel-group comparison of Acthar Gel with Placebo Gel in active systemic lupus erythematosus. It specifies the treatment schedule, the primary PGA measure, its direction, and the stated assessment times. It also reports selected adverse-event counts and lists secondary outcomes. Those elements establish what the study was designed to examine and identify some reported safety information.
The record does not report numerical primary-outcome results, a treatment-group estimate, a confidence interval, or a p-value. It therefore does not establish the direction, magnitude, or precision of a PGA difference. The description of lower scores as improvement is a property of the scale, not an outcome finding. Secondary outcome names likewise do not indicate whether scores or event counts differed between groups.
In general, statistical significance and clinical importance are distinct. A result may be estimated precisely but have limited practical importance, or have an important point estimate but substantial uncertainty. Assessing either requires the estimate, its uncertainty, and relevant clinical context. Those primary outcome details are not reported in the registry record.
The safety counts indicate how many participants were recorded as affected in each group for the listed categories. They do not by themselves establish causality, comparative risk, or the overall safety profile. The registry information does not report the event-level context, statistical uncertainty, or complete details needed for those interpretations. The trial's completed status also does not substitute for numerical results.
The appropriate reading is therefore limited: the registry record documents the design, outcome definitions, and selected safety counts, while leaving the primary efficacy result and key analytical details unreported. Neither a positive nor a negative efficacy conclusion can be drawn from the information in the record.
13. Why This Trial Matters Statistically
This trial is statistically notable for the contrast between a clear design description and the absence of reported primary outcome estimates in the registry record. Randomization, masking, a placebo comparator, and a defined continuous endpoint describe an approach to comparing groups. However, the result cannot be evaluated from the endpoint definition alone. The mean PGA scores, variability, group contrast, and uncertainty are not reported.
The primary measure is assessed at Baseline, Week 16, and Week 24. Multiple time points and several listed secondary outcomes make the analysis plan relevant to interpretation: readers would need to know which contrast was primary and how multiplicity was handled. Those details are not reported in the registry record. This illustrates a general statistical point: design features and outcome lists do not replace a prespecified analysis description or reported estimates.
The safety information also illustrates why counts require context. The record gives numbers of participants affected and identifies participants at risk, but it does not provide a comparative analysis or uncertainty estimates. Descriptive event counts can support a factual account of what was recorded without supporting a causal conclusion.
Finally, the record describes a sample-size planning illustration based on a fraction of an observed effect and stated assumptions. Such an illustration is not observed power and is not a substitute for the trial's original sample-size justification, which is not reported in the registry record. Taken together, the statistical importance lies in distinguishing what the registry documents from what remains unavailable for evaluating the study's outcome estimates.
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 trial-specific details needed to evaluate the reported outcomes are not reported in the registry record. The numerical PGA results are absent, including group means, standard deviations, and between-group estimates at the listed assessment times. Confidence intervals, p-values, and the analysis method for the primary outcome are also not reported. Consequently, the registry information does not allow assessment of the estimated effect's size or precision.
The record does not explain how repeated measurements were incorporated, whether the primary comparison used change from Baseline or scores at a follow-up time, or whether baseline values were adjusted for. It does not describe handling of missing measurements, analysis-population membership beyond the mITT wording, or sensitivity analyses. These omissions limit assessment of the robustness of any outcome analysis.
Although several outcomes and time points are listed, the registry does not report the multiplicity plan or identify a testing hierarchy. The trial's sample-size justification, randomization procedures, allocation concealment, and details of who was masked are not reported in the registry record. These omissions do not show that procedures were absent; they mean the registry information does not describe them.
The safety information is also limited to selected counts and serious-event terms. Event definitions, timing, participant-level overlap, and comparative uncertainty are not reported in the registry record. No numerical results for the listed secondary outcomes are reported. These limitations mean the available information supports a description of the study's registered design and selected safety observations, but not a complete evaluation of efficacy, safety, or analytical robustness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Acthar Gel for Active Systemic Lupus Erythematosus (SLE) — NCT02953821.
- Registry record last updated 2020-08-20; status last verified 2020-08.
- Results first posted 2020-08-20.
- 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.
Continue through the Clinical Biostats statistical pathway
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18. Record Summary
NCT02953821 is a completed Phase 4 randomized, double-blind, parallel-group, placebo-controlled study sponsored by Mallinckrodt. The registry lists enrollment of 172 participants and compares Acthar Gel with Placebo Gel in active systemic lupus erythematosus. Both groups followed the same 24-week schedule: every other day for 4 weeks, then twice per week for 20 weeks.
The primary outcome is mean Physician's Global Assessment score at Baseline, Week 16, and Week 24, in the mITT population with a score at the given week. Higher PGA scores indicate more severe disease activity; lower scores indicate improvement. Numerical primary and secondary outcome results are not reported in the registry record. Selected adverse-event counts, deaths, and serious-event terms are reported, but no inferential safety comparison is given.