Study of H.P. ACTHAR Subcutaneous Gelatin (Gel)(Highly Purified Gel Injection) in Uveitis Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of H.P. ACTHAR Subcutaneous Gelatin (Gel)(Highly Purified Gel Injection) in Uveitis Patients (NCT02764697), a na phase 4 study. The primary outcome is Number of Participants With Photographic Haze Reduced to Grade 0 or Down 2 Steps Documented With Fundus Photography.

2. Clinical Question

The clinical question is about an observed change in a photographic measure during treatment, rather than a comparison of treatment strategies. The endpoint focuses on intermediate uveitis haze, graded on a photographic scale in which lower values indicate a better outcome. The study summary describes the broader aim as evaluating possible effectiveness in patients with active ocular inflammatory disease who are receiving glaucoma treatment or have a glaucoma history.

Because the study has one group and is open-label, its design cannot distinguish change occurring during the study from change that would have occurred without the intervention. The registry record also does not report the number of participants with the relevant type of uveitis, baseline haze grades, or the outcome count. Those omissions mean the clinical question can be described from the protocol, but the record does not establish how many participants achieved the specified photographic change.

3. Trial Design

This was a Phase 4, prospective, open-label study with a single group. The registry lists allocation as not applicable and masking as none. Enrollment is recorded as 6, and the study status is completed. The record gives a start date of 2016-06-30 and a primary completion date of 2016-12-07. The sponsor is Tampa Bay Uveitis Center, LLC.

Participants received H.P. Acthar subcutaneous gel injection. The intervention description specifies 40 U/ml, twice weekly for 8 weeks followed by once weekly for 4 weeks, with 4 additional doses permitted if resolution is incomplete. The primary outcome was assessed at 12 weeks. The description of the primary measure says fundus photography was planned at baseline and 12 weeks.

The registry describes a population with active non-infectious uveitis and associated glaucoma in the official title. The study summary refers to active ocular inflammatory disease in people currently on glaucoma treatment or with a history of glaucoma. The conditions listed include uveitis, anterior, intermediate and posterior uveitis, scleritis, and clinically significant macular edema. The record does not state how participants were distributed across these conditions.

There is no randomized comparison or separate control group. Results from a single group can describe what was recorded among participants, but cannot by themselves show how outcomes would have differed under another treatment or without treatment. The registry record does not report additional protocol details about adherence, treatment changes, or the use of the optional doses.

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: The patient after consent was given, were required to have their medical records reviewed and have screening laboratory evaluations

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Photographic Haze Reduced to Grade 0 or Down 2 Steps Documented With Fundus Photography, measured over 12 Weeks.

The primary endpoint is the number of participants whose photographic haze was reduced to grade 0 or improved by 2 steps, documented with fundus photography. The registry specifies a 12-week timeframe and describes fundus photographs at baseline and 12 weeks. It notes that intermediate uveitis is graded by haze using a photographic scale from grades 0-4, based on the Nussenblatt photographic vitreous haze scale and used with the SUN criteria. Lower values represent a better outcome.

A threshold-based endpoint turns a graded measurement into a count of participants who meet a prespecified response definition. This can make the outcome clinically interpretable as a defined photographic change, while retaining a simple count as the reported measure. It also means that the endpoint does not convey the full pattern of changes: participants who improve by less than the threshold and participants with no change are not distinguished by the endpoint as worded.

The registry record does not report the number meeting the threshold, the number assessed at follow-up, or the distribution of photographic grades. It therefore allows the endpoint definition to be explained, but not the observed response rate or the degree of precision around it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study records outcomes among participants who receive the intervention, without a separate concurrent group assigned to a different intervention or to no intervention. Its direct statistical description is the observed outcome in that group. This can be useful for documenting what was recorded during a study, but it does not supply the counterfactual outcome: what would have happened to the same participants under another approach or without the study intervention.

That distinction matters when interpreting change from baseline. A change between baseline and follow-up may coincide with treatment, but the design alone cannot establish that treatment caused the change. The disease course, other care, participant selection, and measurement variability may also be relevant. The registry record does not report enough information to assess these possibilities.

What does the endpoint count?

The primary endpoint is a participant count defined by a photographic threshold: haze reduced to grade 0 or down 2 steps, assessed at 12 weeks. A thresholded outcome is different from reporting every value on the underlying scale. It classifies participants according to whether they meet the stated criterion, rather than describing the whole distribution of grades or each participant’s precise change.

Binary outcomes are often summarized as counts of participants meeting a criterion and counts not meeting it. To interpret such a summary, readers need to know who was assessed and how missing outcome measurements were handled. The registry record names the endpoint but does not report the observed count, the number assessed at 12 weeks, or missing-data handling. It is therefore not possible to reconstruct a response proportion or its uncertainty from the registry record.

Why does the scale description matter?

The registry states that intermediate uveitis is graded by photographic haze on grades 0-4, with lower values indicating a better outcome, and describes the scale as based on the Nussenblatt photographic vitreous haze scale and used with the SUN criteria. A defined scale supports consistent interpretation when measurements are made and interpreted consistently. However, the record does not report details such as who graded the images, whether grading was independently reviewed, or how disagreements were handled. With no masking, knowledge of treatment assignment would not be concealed from participants or study personnel, although the record does not specify whether image graders were masked.

What can a confidence interval tell a reader?

In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not remove limitations in the design, such as the lack of a comparison group, and it does not account automatically for bias or unmeasured differences. The registry record does not report a confidence interval or an estimate for the primary endpoint, so precision cannot be evaluated from the posted results.

What is the role of statistical tests?

In general, a statistical test evaluates how compatible observed data are with a specified null hypothesis under a model. A test result is not a measure of clinical importance, and a non-significant result would not establish that no effect exists. Tests also depend on the analysis plan, data quality, and assumptions. The registry record lists no analyses, and it does not report a test or a p-value for the primary endpoint. No conclusion about statistical significance can therefore be drawn from this record.

How should planning calculations be distinguished from findings?

Sample-size calculations are planning illustrations: they describe the number of participants a hypothetical study might require under stated assumptions. They are not observed outcomes and are not evidence that a study had a particular probability of detecting an effect. The planning assumptions described for the associated illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a fraction of the observed effect. For time-to-event calculations, the stated convention is a total number of events; other calculations use participants per arm.

Those assumptions describe a hypothetical two-arm calculation, whereas this trial is registered as a single-group study with no randomized comparison. The registry record does not report the observed effect needed to interpret such calculations, nor does it provide trial-specific sample-size justification. The calculations should not be read as the study’s actual design, observed power, or evidence that the study could reliably detect a particular effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and 0 analyses. It identifies the photographic haze count as the primary outcome, but does not provide details about the other outcome measure or report results for either outcome. The record does not describe a prespecified strategy for handling multiple outcomes or multiple statistical tests. Multiplicity can matter because examining several outcomes or analyses can increase the chance of finding an apparently notable result by chance. Without the analysis plan and results, it is not possible to assess whether or how that issue was addressed.

Missing-data handling is not reported in the registry record. In particular, the record does not give the number of participants with a 12-week photograph, describe reasons for any unavailable measurements, or explain whether missing outcomes were excluded, imputed, or handled in another way. These details matter because an outcome count among participants with available photographs can differ in interpretation from a result that accounts for missing measurements.

The registry record also does not define analysis populations, such as which participants were included in the primary outcome analysis or how treatment exposure and protocol deviations were handled. Enrollment is reported as 6, while the safety groups list 5 at risk; the record does not explain that distinction. Neither count should be assumed to define the primary analysis population. With no analysis results and no documented handling of missing data or analysis populations, the primary endpoint cannot be interpreted as a complete estimate for all enrolled participants.

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.

For H.P. Acthar Subcutaneous Gel Injection, the registry records 5 participants at risk for serious adverse events and 0 affected. It records 5 at risk for other adverse events and 0 affected, with 0 deaths. These counts are the safety figures reported in the registry record. They do not establish that every enrolled participant was included in safety follow-up: enrollment is recorded as 6, and the record does not explain why the at-risk count is 5.

A zero count means no affected participants are recorded for the listed category; it does not prove that the risk is absent. Counts from a small, single-group study can provide limited information about uncommon events, and the registry does not report details about safety monitoring, duration of observation, or event-specific descriptions. No serious adverse event terms are listed. The record therefore supports only a narrow description of the recorded counts, not a broad conclusion about safety.

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

The study record establishes that a completed, open-label, single-group trial of H.P. Acthar was registered, with enrollment of 6 and a primary photographic haze outcome specified for 12 weeks. It also gives the planned intervention schedule and limited safety counts. These registry entries describe the study’s design and the outcomes it intended to assess.

The record does not report the primary outcome result. It does not say how many participants met the photographic threshold, how many had follow-up photographs, or how the underlying grades changed. Therefore it cannot show the size of any observed change, or how precisely that change was estimated. The listed safety counts are similarly limited and do not establish that no adverse events occurred beyond those recorded in the registry.

Even if outcome changes were available, a single-group study would not provide a randomized comparison. It could describe outcomes during treatment but could not, on its own, attribute changes to the intervention or compare it reliably with another approach. The open-label design and absence of a concurrent control group are important when judging what the study can establish.

The registry record also does not report a statistical analysis, an analysis population, missing-data methods, or a trial-specific sample-size justification. Those omissions prevent a fuller assessment of precision, completeness, and analytical choices. The appropriate conclusion is limited: the registry documents the study’s intended question and design, but does not provide enough outcome information to determine what the primary endpoint showed.

13. Why This Trial Matters Statistically

This study matters statistically because its design illustrates the difference between documenting outcomes and estimating a comparative treatment effect. A single-group study can record whether participants met a defined endpoint during follow-up, but the absence of a concurrent comparator limits causal interpretation. That distinction is especially important when a study is open-label and the endpoint depends on assessment of images.

The endpoint itself also illustrates a common trade-off. A threshold such as grade 0 or a reduction of 2 steps is easy to describe as a count of participants meeting a criterion. At the same time, a threshold discards information about the range of grades and changes that do not meet the criterion. The registry does not report the count or the underlying distribution, so readers cannot assess either the threshold result or the broader pattern of measurements.

Transparency about outcome reporting is essential to statistical interpretation. Here, the registry identifies the primary outcome and timeframe but lists no analyses and gives no primary result. The safety record includes counts, yet its at-risk denominator differs from the enrollment figure and the reason is not reported. These gaps demonstrate why counts need context, including who was assessed, how outcomes were handled, and what analysis population was used.

Finally, planning calculations should be kept separate from trial findings. Hypothetical calculations based on two-arm assumptions do not change the registered single-group design and do not show that the trial had adequate power. The record does not report the observed effect or a trial-specific rationale for enrollment. These distinctions help prevent planning assumptions or sparse registry entries from being mistaken for evidence of efficacy or precision.

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 is the absence of a reported primary outcome result. Although the registry defines photographic haze improvement at 12 weeks, it does not give the number meeting that definition, the number assessed, or the distribution of grades. The registry also lists 0 analyses, so no statistical estimate or uncertainty measure is available.

The single-group, open-label design has no concurrent control and no randomized allocation. Outcomes therefore cannot support a controlled comparison, and changes during follow-up cannot be attributed to the intervention on the basis of this design alone. The record does not state whether image graders were masked or describe image-reading procedures.

Enrollment is recorded as 6, but the safety group lists 5 participants at risk. The reason for this difference is not reported in the registry record. The record also does not describe the primary analysis population, follow-up completeness, missing-data handling, adherence, or use of the optional additional doses. The eligible population and distribution across the listed ocular conditions are not further characterized.

The registry does not report a trial-specific sample-size justification, analysis plan, multiplicity strategy, or detailed safety follow-up. The listed planning assumptions concern a hypothetical two-arm calculation and do not match the registered single-group design. Taken together, these reporting and design limitations restrict interpretation to the study’s stated aims, protocol description, and recorded safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of H.P. ACTHAR Subcutaneous Gelatin (Gel)(Highly Purified Gel Injection) in Uveitis Patients — NCT02764697.
• Registry record last updated 2018-07-02; status last verified 2018-06.
• Results first posted 2018-07-02.
• 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

NCT02764697 is a completed, Phase 4, prospective, open-label, single-group study sponsored by Tampa Bay Uveitis Center, LLC. The registry records enrollment of 6, a start date of 2016-06-30, and a primary completion date of 2016-12-07. The intervention was H.P. Acthar subcutaneous gel injection, with the protocol describing 40 U/ml and a scheduled course followed by an option for additional doses if resolution was incomplete.

The primary outcome was the number of participants with photographic haze reduced to grade 0 or down 2 steps at 12 weeks. The registry lists 2 outcome measures and 0 analyses, but does not report the primary outcome count or its statistical uncertainty. Serious adverse events and other adverse events each have 0 affected among 5 at risk; deaths are recorded as 0. The registry does not explain the difference between the enrollment figure and safety denominator.