Double-Blinded, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Biochemical Activity of Intravenous Cpn10 Administration in Subjects With Mild to Moderate SLE.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Double-Blinded, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Biochemical Activity of Intravenous Cpn10 Administration in Subjects With Mild to Moderate SLE. (NCT01838694), a randomized phase 1, phase 2 study. The primary outcome is Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort..

2. Clinical Question

3. Trial Design

This completed study is recorded as a randomized, double-blinded, parallel-group, placebo-controlled trial in people with mild to moderate SLE. The trial record lists PHASE1 and PHASE2. Its stated primary objective was to evaluate the safety, tolerability, and efficacy of 4 weeks of intravenous Cpn10 treatment in participants with mild to moderate active SLE. The sponsor is Invion, Inc.; the recorded start is 2013-07 and primary completion is 2015-08.

The active intervention was Ala-Cpn10, described as recombinant minimally modified Chaperonin10. The registry distinguishes cohorts by dose and SLE severity: 10mgs in mild SLE, 30mgs in mild SLE, 100mgs in mild SLE, and 30mgs in moderate SLE. The active regimen description gives a range from 10mg twice weekly to 100mg twice weekly, administered intravenously by infusion over 60 minutes. The placebo was matched vehicle without active ingredients, also administered intravenously over 60 minutes. Further details of dose assignment, sequence generation, concealment, and infusion scheduling are not reported in the registry record.

For the IL-6 endpoint, the posted outcome data are separated into the placebo cohort and the dose-and-severity cohorts. The number of participants with endpoint results differs across those groups: the registry lists 5 for placebo, 5 for 10mgs in mild SLE, 4 for 30mgs in mild SLE, 3 for 100mgs in mild SLE, and 1 for 30mgs in moderate SLE. These are endpoint analysis counts, not a statement about the total randomized allocation to each cohort. The registry’s overall enrollment is 30, while the safety groups have different at-risk counts. The relationship between these analysis populations and all enrolled or randomized participants is not fully described.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis Population reflects participants for whom adequate analyzable samples were collected

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 Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort., measured over 4 weeks.

The primary outcome is change from baseline in serum interleukin 6 (IL-6) levels at the end of active dosing, with the timeframe specified as 4 weeks. IL-6 is a measurable biological marker, and a change in its serum level can be used to describe a biochemical response over the treatment period. This endpoint is reported as mean percentage change from baseline, with standard deviation as the measure of spread.

The registry identifies the analysis population as participants for whom adequate analyzable samples were collected. This definition makes the availability and adequacy of blood samples relevant to who contributes to the posted endpoint summaries. The record does not give details about sample collection procedures, assay characteristics, how a percentage change was calculated, or how measurements below an assay limit would be treated; those details are not reported in the registry record.

The endpoint addresses biochemical activity rather than directly reporting symptoms, disease activity, functioning, or longer-term outcomes. The trial’s broader stated objective included safety, tolerability, and efficacy, but the posted primary outcome is specifically IL-6 change. A biomarker can be informative about biological activity, yet its numerical movement alone does not establish how a participant feels or functions, nor does it establish a clinical benefit. The registry record does not report a validated relationship between the IL-6 endpoint and those other outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the reported means and standard deviations describe?

For a continuous outcome, a mean gives the arithmetic average of the observations included in a group summary. In this study, the quantity being averaged is percentage change from baseline in serum IL-6 at 4 weeks. A positive mean indicates an average increase under the usual interpretation of change from baseline, while a negative mean indicates an average decrease. The mean alone does not show whether most participants changed in that direction, whether a small number of observations drove the average, or how the individual values were distributed.

The standard deviation describes the spread of observations around a group mean. It is not the uncertainty interval for the mean and does not directly give the range of individual responses. The large standard deviation in the 10mgs mild-SLE cohort, alongside its mean of 987.7, signals substantial dispersion in that small group. General statistical principle: when observations vary widely, a group average may be a poor description of a typical participant, and estimates based on a small group can be especially sensitive to individual values.

Why are confidence intervals useful?

A confidence interval communicates the precision of an estimated quantity by giving a range of values compatible with the data and the method used. General statistical principle: wider intervals indicate less precision, while narrower intervals indicate greater precision, conditional on the analysis assumptions. The registry record does not report confidence intervals for the IL-6 summaries or for comparisons with placebo. Without them, readers cannot assess the uncertainty around a treatment contrast from the posted results. Standard deviations cannot be substituted for confidence intervals because they describe variation among observations rather than precision of an estimated mean or contrast.

What is missing from the inferential analysis?

No statistical analyses are listed for this continuous endpoint. In particular, the record does not give a model, an estimated contrast against placebo, a standard error, a confidence interval, or a significance test. It does not report adjustment for baseline IL-6 or other participant characteristics. Randomization is a design feature, but the fact of randomization does not supply the missing analysis or make the descriptive summaries equivalent to a treatment-effect estimate.

General statistical principle: a comparison of several active dose and severity cohorts with a placebo group can be affected by variability, small group sizes, and the number of comparisons. A prespecified model can define how those comparisons are made and how uncertainty is quantified. The statistical plan, including any planned covariate adjustment, handling of repeated measurements, or multiplicity strategy, is not reported in the registry record. No particular method should therefore be assumed to have been used.

How should planning calculations be understood?

The registry record describes a sample-size 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 describes non-time-to-event results as participants per arm for 80% power or other stated planning targets when applicable. Such calculations are planning illustrations, not observed power and not evidence that the trial had a particular chance of finding an effect. No calculated planning estimates are included in the available record, so no required sample size can be stated from it.

General statistical principle: planning estimates depend on assumptions about the effect to detect, variability, allocation, and analysis method. If an observed effect from a small, noisy study is used as the planning input, the resulting illustration may be unstable. It should not be confused with the precision or strength of evidence in the completed trial. The record also does not report a sample-size justification for the trial’s actual design, and that rationale should not be inferred from the planning assumptions.

Why does over-dispersion matter?

Over-dispersion is a general term for variability greater than a chosen statistical model expects. The endpoint summaries are means and standard deviations, and the 10mgs mild-SLE cohort has a particularly large reported spread. This does not establish a specific statistical distribution or prove over-dispersion under a model, since no model is reported. It does make clear that a single average may conceal markedly different values. General statistical principle: a model that underestimates variability can produce intervals that are too narrow and tests that are too optimistic. Examining individual observations and using an analysis suited to the data would help evaluate this issue, but those materials and details are not reported in the registry record.

The moderate-SLE active cohort has only one endpoint observation, so its standard deviation is recorded as 0.0. With a single observation, there is no within-cohort information to estimate participant-to-participant variation. That reported value is a consequence of the available summary and should not be interpreted as a meaningful estimate of population variability. Overall, the registry offers descriptive endpoint statistics but does not report the inferential methods needed to quantify treatment contrasts or their precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry record describes one primary outcome measure and lists no secondary outcomes. It does not report a statistical analysis for the primary outcome or a multiplicity strategy. Because the posted endpoint is divided across several active dose-and-severity cohorts and placebo, readers should not assume that a prespecified plan determined which comparisons were primary, how multiple comparisons were handled, or whether any analyses were exploratory. Those details are not reported in the registry record.

The endpoint population is defined as participants for whom adequate analyzable samples were collected. The record lists endpoint counts by cohort, but does not explain why the outcome counts differ from one cohort to another, how many participants lacked adequate samples, or whether missingness was related to treatment, severity, baseline IL-6, or clinical status. It also does not describe an imputation method, a sensitivity analysis, or a rule for excluding incomplete measurements. The posted group summaries therefore apply to the analyzable samples and cannot be assumed to represent every enrolled participant.

The record does not explain whether the outcome analysis followed an intention-to-treat principle, a per-protocol approach, or another analysis population definition beyond the analyzable-sample description. It does not report whether participants who stopped treatment or missed visits were included in the endpoint analysis. Such choices can affect interpretation, particularly when the available endpoint groups are small. The reasons for missing data and the methods used to address them are not reported in the registry record, limiting assessment of potential bias.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypotension (4.5%).

The safety summaries use at-risk counts of 8 for placebo and 22 for Ala-Cpn10. Serious adverse events are reported for 0 of 8 in the placebo group and 1 of 22 in the Ala-Cpn10 group. Other adverse events are reported for 4 of 8 in the placebo group and 6 of 22 in the Ala-Cpn10 group. These are descriptive counts as posted; they do not establish that an event was caused by the intervention or that the groups are meaningfully different.

The registry lists Hypotension at 4.5% as a top serious term, but does not state in the available record which group the term belongs to or provide event-level details. Death counts are not reported in the registry record. The record also does not give the seriousness criteria, timing, duration, outcome, or attribution of individual events, nor does it provide detailed exposure-adjusted rates. The at-risk group counts should not be confused with the smaller endpoint analysis counts: they describe the safety summaries, while the IL-6 summaries use the separately listed analyzable-sample populations.

General statistical principle: in a small study, adverse-event counts are imprecise, and absence of a recorded event in a group does not establish absence of risk. These safety figures are useful for describing what the registry reports, but they are not sufficient to characterize uncommon harms or compare risks precisely.

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

The results establish that the registry contains descriptive summaries of mean percentage change in serum IL-6 from baseline at 4 weeks for placebo and several Ala-Cpn10 dose-and-severity cohorts. Those summaries include means, standard deviations, and the number of analyzable observations in each cohort. They show marked variation in the reported group means and spread, including a very large mean and standard deviation for 10mgs in mild SLE and a single-observation summary for 30mgs in moderate SLE.

The posted results do not establish that Ala-Cpn10 changed IL-6 relative to placebo. No treatment contrast, confidence interval, or significance test is reported, and the small endpoint groups and variability limit precision. The data also do not establish whether a change in IL-6 corresponds to a change in SLE symptoms, disease activity, functioning, or longer-term health outcomes. The registry record does not report results for those outcomes in the information available for this analysis.

The record’s description of a randomized, double-blinded, placebo-controlled design matters because those design features are intended to support fair comparisons. But design alone is not enough to interpret the effect: the allocation details, analysis plan, missing-data handling, and inferential results are not reported. Nor can a result from the analyzable samples be automatically generalized to all participants enrolled in the trial.

The safety summaries report one serious adverse event among 22 at risk in the Ala-Cpn10 group and none among 8 at risk in the placebo group, alongside the posted counts for other adverse events. These counts do not demonstrate cause, comparative safety, or the frequency of rare events in a broader population. Taken together, the record supports a cautious description of what was measured and recorded, not a definitive conclusion about efficacy or safety.

13. Why This Trial Matters Statistically

This study is statistically instructive because a randomized design and a numerical biomarker result do not by themselves provide a precise treatment-effect estimate. The registry separates the IL-6 outcome into several active cohorts defined by dose and SLE severity, with limited analyzable counts in each. The means vary greatly, and the spread is substantial in at least one cohort. Those features make it important to distinguish descriptive statistics from a planned comparison and to ask how much uncertainty surrounds each estimate.

It also illustrates why analysis populations matter. The endpoint is defined for people with adequate analyzable samples, while safety summaries use different at-risk counts. Without an account of missing samples and the relation between these populations, readers cannot tell whether the endpoint summaries represent the full randomized groups or a selected subset. The record’s lack of an inferential analysis means no reported statistical framework connects the cohort summaries to a comparison against placebo.

Finally, a biomarker endpoint can answer a focused biochemical question without resolving broader clinical questions. The posted outcome concerns serum IL-6 change over 4 weeks; it is not, by itself, evidence about symptoms, disease control, or longer-term outcomes. The study therefore highlights the value of transparent reporting of estimates, uncertainty, analysis populations, missing-data methods, and prespecified comparisons alongside the raw descriptive summaries.

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 endpoint analysis groups are small, with reported counts of 5 for placebo, 5 for 10mgs in mild SLE, 4 for 30mgs in mild SLE, 3 for 100mgs in mild SLE, and 1 for 30mgs in moderate SLE. The summary for the moderate-SLE cohort cannot estimate between-participant variability from a single observation. Small groups also make means sensitive to individual measurements, a concern given the large standard deviation reported for 10mgs in mild SLE.

The record does not report individual IL-6 values, baseline distributions, assay performance, or the handling of extreme measurements. It is therefore not possible to determine from the summaries whether the very large means reflect a pattern across participants or are driven by particular observations. No confidence intervals or treatment comparisons are posted, and the statistical model and analysis plan are not reported.

The description of the endpoint population indicates that only participants with adequate analyzable samples contribute, but the reasons for unavailable or inadequate samples are not reported in the registry record. The record does not explain the relation between endpoint counts and randomized allocation, or report whether the analysis used all randomized participants. The safety record also lacks event-level information and does not report deaths. These limitations restrict interpretation of both the biochemical endpoint and the adverse-event summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Double-Blinded, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Biochemical Activity of Intravenous Cpn10 Administration in Subjects With Mild to Moderate SLE. — NCT01838694.
• Registry record last updated 2017-01-30; status last verified 2016-12.
• Results first posted 2017-01-30.
• 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

NCT01838694 is a completed randomized, double-blinded, parallel, placebo-controlled study recorded as PHASE1 and PHASE2. It evaluated intravenous Ala-Cpn10 in participants with mild to moderate active SLE. The registry records a start of 2013-07, primary completion of 2015-08, and overall enrollment of 30.

The primary outcome was mean percentage change from baseline in serum IL-6 at 4 weeks, with standard deviation reported for each listed cohort. The endpoint population comprised participants for whom adequate analyzable samples were collected. Results are descriptive, and no statistical analyses are listed. The safety record reports serious and other adverse-event counts by group, but does not report deaths. The registry record does not provide the inferential analysis, missing-data methods, or fuller safety details needed for a definitive assessment of comparative outcomes.