A Study to Evaluate Safety of Three Intra-articular Injections of Ampion in the Knee of Adults With Osteoarthritis Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Safety of Three Intra-articular Injections of Ampion in the Knee of Adults With Osteoarthritis Pain (NCT02184156), a randomized phase 1, phase 2 study. The primary outcome is Change in Knee Pain (Phase 2).

2. Clinical Question

3. Trial Design

This was a prospective Phase 1/2 study, described as randomized, double-masked, and parallel-group. Its stated focus was the safety and exploratory efficacy of three intra-articular Ampion injections administered two weeks apart to adults with pain due to osteoarthritis of the knee. The registry lists the study as completed, with a total enrollment of 47. The study start is listed as 2014-06 and primary completion as 2015-10.

The two phases had different stated roles. Phase 1 evaluated safety after three injections. The brief summary says Phase 2 enrollment would begin in the absence of serious drug-related adverse events or unanticipated drug-related adverse events in Phase 1. Phase 2 evaluated efficacy and safety. The registry record does not report the operational criteria used to determine whether Phase 2 enrollment could proceed, or how that decision was documented.

The Phase 2 primary outcome compared Ampion 4 mL injection with placebo 4 mL injection. The posted primary results list 20 participants in each arm and identify the analysis population as ITT. The record also lists a Phase 2 knee-function outcome. Phase 1 safety results are reported separately from Phase 2 safety results. The overall enrollment should not be read as the sample size for every outcome: the record provides outcome-specific group counts, and the safety groups include a separate Phase 1 group.

The registry lists three outcome measures and two analyses, while one secondary outcome is posted in the available results. The protocol, full inclusion and exclusion criteria, recruitment setting, and detailed participant flow are not reported in the registry record. The record also does not explain how the planned Phase 1 and Phase 2 portions were incorporated into one final analysis, beyond the phase-specific descriptions and posted group results.

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: No pharmacological or non-pharmacological treatment targeting osteoarthritis (OA) started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study.

Phase 1 Safety

Phase 2 20 Week Efficacy

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population

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: Phase 1 Safety Study Population; Phase 2 20 Week Efficacy Population

6. Primary Endpoint

The registry lists the primary outcome as Change in Knee Pain (Phase 2), measured over Scored at Baseline and 20 Weeks.

The primary endpoint is mean change in WOMAC A Pain score, a measure of knee pain. The registry describes the WOMAC scale as a 5-point Likert scale, ranging from 0 for none to 4 for extreme. The outcome is expressed as the change from baseline, with a negative difference indicating decreased pain and a more negative value indicating a greater reduction. The listed population is ITT.

Change from baseline is used to express how the score changed during follow-up relative to each participant’s starting score. Comparing the average change between randomized groups provides an estimate of the difference in average change associated with assignment to the two study arms, subject to the analysis and follow-up information available. It does not describe every participant’s experience: a group mean can conceal variation in individual changes, which is why the posted standard deviations are relevant alongside the means.

There is an inconsistency in the registry’s timing descriptions. The primary outcome timeframe says scores were assessed at baseline and 20 weeks, while the outcome description says the mean change was from baseline to 12 weeks. The registry record does not resolve which time point corresponds to the posted primary result. That ambiguity matters because an endpoint’s interpretation depends on when it was measured. No prespecified clinically important difference or other threshold for interpreting the size of the change is reported in the registry record.

7. Results Posted in the Registry

• Ampion 4 mL Injection: mean -1.41 versus -0.85 on control; difference -0.56 (95% CI -1.01 to -0.11), standardized effect d = -0.77; z-test p = 0.015.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in Knee Function (Phase 2)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ampion < 5 kDa Ultrafiltrate of 5% HSA: mean -1.27 versus -0.98 on control; difference -0.29 (95% CI -0.76 to 0.18), standardized effect d = -0.39; z-test p = 0.223.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ampion < 5 kDa Ultrafiltrate of 5% HSA and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts one secondary outcome, change in knee function, with results for the Phase 2 Ampion and placebo arms. Its recalculated mean difference is -0.29, and the confidence interval includes zero. The reported sponsor test gives p = 0.25, compared with an unadjusted recalculated p-value of 0.223. These findings are less conclusive statistically than the primary pain comparison, whose recalculated confidence interval lies below zero. The overall pattern therefore does not provide equally clear statistical evidence across the primary and posted secondary outcomes.

The knee-function outcome is related to the primary pain outcome because both concern changes in knee-related scores during the study. However, the secondary result is not a substitute for the primary result and should not be used to strengthen the primary finding as if it were an independent replication. The registry’s outcome list includes three outcome measures, but only one secondary outcome is posted in the results described by the record. The status and results of any other measures are not reported in the registry record.

Unadjusted secondary analyses carry less weight when multiple outcomes or comparisons are examined. Each additional test creates another opportunity to observe a result that appears notable by chance. A multiplicity adjustment can address that issue, but the registry record does not report whether any adjustment was planned or applied. Without that information, the secondary analysis is best read as exploratory. Its p-value should not be treated as though it were the sole prespecified test, and it does not establish that the groups had no difference.

The registry does not state a formal hierarchy for the outcomes, clarify whether the secondary analysis was prespecified in the final statistical plan, or report how missing data were handled for it. The posted pattern is therefore informative as a description of the available outcome results, but it cannot resolve questions about confirmatory status or multiplicity control.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in Knee Function (Phase 2)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a score measured on a scale, and the registry reports its mean and standard deviation for each arm. A mean gives the arithmetic average of the observed scores or changes. It is a useful summary of the group’s central result, but it does not imply that all participants had the same change. The standard deviation describes how dispersed the observations are around the mean. Larger dispersion means individual observations vary more widely, which can make a group mean less precise for a fixed sample size.

What does the mean difference represent?

The mean difference compares the Ampion group’s average change with the placebo group’s average change. For the primary outcome, the reported recalculation is -0.56, based on the group means -1.41 and -0.85. Because the registry defines more negative change as a greater reduction in pain, a negative difference points toward a larger average decrease in the Ampion arm. The estimate is on the WOMAC A Pain change scale; it is not a percentage, a risk ratio, or a count of participants who improved. The registry does not report a clinically important difference threshold that would give this score difference a separate clinical interpretation.

Why use a t-test?

A two-sided t-test assesses whether the observed difference in group means is sufficiently inconsistent with a null hypothesis of no difference, under the assumptions of the test. “Two-sided” means the test allows for a difference in either direction rather than testing only for a larger or smaller mean in one prespecified direction. The registry reports a two-sided t-test for the primary and secondary comparisons. The record does not report additional details such as diagnostics, adjustments, or a fuller specification of the test implementation.

The recalculated tests are unadjusted comparisons based on the posted group summary statistics. A t-test uses information about the mean difference and its uncertainty, which depends in part on the variability and number of observations in the groups. The registry reports 20 participants in each Phase 2 primary arm. The posted standard deviations are used in the recalculation; no individual participant data are available in the registry record. A summary-statistic recalculation cannot reproduce analysis choices that depend on individual records unless those choices are fully represented in the summaries.

What does a p-value say?

A p-value describes how compatible the observed data are with a specified null hypothesis under the statistical model used. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of a difference. The registry reports p = 0.02 for the primary analysis, while the unadjusted recalculation gives p = 0.015. For the secondary outcome, the reported value is p = 0.25 and the recalculated value is 0.223. The registry record does not explain the differences. A p-value should be read alongside the estimated difference, confidence interval, outcome definition, and limitations in the record.

Why report a confidence interval?

A confidence interval gives a range of values compatible with the data and the statistical method at the stated confidence level. It shows the uncertainty around an estimate more directly than a p-value alone. The primary recalculated interval lies below zero, whereas the secondary interval includes zero. An interval including zero indicates that the data do not rule out no mean difference at the corresponding level of confidence; it does not prove that there is no difference. The confidence level itself is not reported for the posted sponsor analysis, and the registry’s reported analysis does not include interval bounds.

What is the role of planning illustrations?

The planning figures are illustrations based on fractions of the observed effect, an equal allocation between two arms, a two-sided significance level of 0.05, and a normal approximation. They show the number of participants per arm associated with the stated power targets under those assumptions. They are not the trial’s original sample-size justification, and the registry record does not report the original design assumptions. Smaller effects require more participants to detect under otherwise comparable planning assumptions, because a smaller group difference is harder to distinguish from variation in the outcome.

These concepts are general statistical explanations. The registry record does not report whether the original trial used the same methods or assumptions as the recalculations and planning illustrations, except for the stated sponsor analyses and their two-sided t-test description. In particular, the original sample-size justification, missing-data procedures, interim analyses, and detailed statistical plan are not reported in the registry record.

11. Confidence Intervals and Precision

The primary recalculated mean difference is -0.56. Its confidence interval lies entirely below zero, which indicates that the interval is consistent with a negative difference in average change under the recalculation’s assumptions. It also gives a range of plausible values around the estimate rather than treating -0.56 as exact. The bounds are not repeated in text because their posted precision exceeds three decimal places. The registry’s own primary analysis reports a two-sided p-value but does not report a confidence interval.

Precision is distinct from direction. The point estimate describes the direction and magnitude of the average difference, while the interval conveys uncertainty about that estimate. An interval can exclude zero and still include effects of differing sizes. Without a prespecified threshold for a clinically important difference, the interval cannot by itself determine whether its values represent a meaningful benefit. The registry record does not report such a threshold.

For the secondary knee-function comparison, the recalculated confidence interval includes zero. That interval is compatible with a range of possible mean differences that includes no difference, as well as differences in either direction. This is not proof that the groups were identical. It indicates that the secondary estimate is imprecise enough that the posted summary statistics do not clearly distinguish it from zero under the recalculation.

The primary outcome’s timing is also uncertain in the registry description: one field names baseline and 20 weeks, while the outcome description says baseline to 12 weeks. Confidence intervals quantify statistical uncertainty under an analysis; they do not resolve uncertainty about which follow-up time the estimate represents, whether observations were missing, or whether the analysis followed the planned approach. Those details are not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect and the stated effect fractions, with equal allocation between the two arms, a two-sided significance level of 0.05, and a normal approximation. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

For the primary comparison, the listed planning figures are 27 participants per arm for 80% power and 36 participants per arm for 90% power when planning for 100% of the observed effect. Planning for 75% of the observed effect gives 48 participants per arm for 80% power and 64 participants per arm for 90% power. Planning for 50% of the observed effect gives 107 participants per arm for 80% power and 143 participants per arm for 90% power.

In plain terms, 80% power describes the probability of detecting an effect of the chosen size under the planning assumptions if that effect is present. The 90% column uses a higher detection probability target. Achieving that higher target generally calls for more participants under otherwise comparable assumptions. The rows illustrate that smaller effects need more participants: an effect set at a smaller fraction of the observed estimate is harder to distinguish from random variation.

These figures are planning illustrations, not observed power. They do not establish what the trial was designed to detect, whether its original design met a target, or how likely its findings are to be true. They depend on using the observed effect as a planning reference, which may not represent the effect in a future study. The registry record does not report the original sample-size justification or assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.560; pooled standard deviation σ = 0.730.
2. n = 2 × (1.96 + 0.842)² × 0.730² / -0.560² = 26.7, rounded up to 27 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.56                      # observed difference in means
sigma <- 0.729965752621313                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2184156)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 27 (80% power), 36 (90% power)
 75% of observed effect: n per arm = 48 (80% power), 64 (90% power)
 50% of observed effect: n per arm = 107 (80% power), 143 (90% power)
power.t.test: 27.7 
Simulated power at n = 27 per arm: 0.792 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary two-sided t-test as p = 0.02. A separate unadjusted recalculation from the posted group summary statistics gives a mean difference of -0.56 and p = 0.015. These values are not identical as displayed. The record does not report the sponsor’s test statistic, confidence interval, or further analytic details that would account for the difference. The registry’s reported result remains the sponsor’s own analysis; the recalculation is a separate summary-statistic calculation, not a replacement for it.

For knee function, the registry reports p = 0.25, while the recalculated unadjusted comparison gives p = 0.223 and a mean difference of -0.29. Again, the registry record does not explain the difference. The posted registry does not mark a discrepancy between sponsor and recalculated results. Neither comparison should be interpreted from the p-value alone: the estimated mean difference, variability, confidence interval, outcome timing, and limitations in reporting all matter.

The registry’s reported analyses identify the method as a two-sided t-test, but do not provide the underlying participant-level data or a full statistical analysis plan. The recalculation uses the posted means, standard deviations, and group counts. Without further analytic details, it is not possible to determine whether differences between the two sets of p-values reflect rounding, implementation, or other analysis choices.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and two analyses, and one secondary outcome is posted. It reports a primary pain outcome and a secondary knee-function outcome, but does not provide a complete account of the remaining outcome measures in the results described. The registry record does not report a multiplicity adjustment, a testing hierarchy, or whether the secondary comparisons were intended to support confirmatory claims. When several outcomes are tested, the chance of at least one apparently notable result can increase; adjustment or a prespecified hierarchy can help control that issue. Without those details, secondary findings should be interpreted cautiously.

The primary analysis population is identified as Intent to Treat (ITT). The registry record does not explain how ITT was implemented, which participants were included in each analysis, or whether any participants were excluded from the posted outcome results. Although the primary arm counts are reported, detailed participant flow and reasons for missing observations are not reported in the registry record.

Missing outcome data can affect group comparisons if the availability of measurements differs between groups or is related to participant outcomes. Statistical approaches may include assumptions about the missingness process or methods for handling incomplete observations, but the registry record does not report which approach was used. It also does not report sensitivity analyses examining alternative assumptions about missing data.

The registry’s primary outcome timing is described inconsistently: the timeframe names baseline and 20 weeks, while the outcome description gives change from baseline to 12 weeks. The record does not clarify the timing used in the analysis. The original statistical analysis plan, interim-analysis procedures, and sample-size justification are not reported in the registry record. These omissions limit assessment of prespecification and analytic robustness; they do not, by themselves, show that the analyses were conducted improperly.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: post procedural haemorrhage (5.0%), eczema (5.0%), embolic stroke (5.0%).

The registry reports serious adverse events by phase and treatment group. In Phase 1, the Ampion group had 0 serious adverse events among 7 participants at risk. In Phase 2, the Ampion group had 3 serious adverse events among 20 participants at risk, while the placebo group had 0 among 20 participants at risk. Deaths are listed as 0 in each of these three groups. These are reported counts, not estimates of comparative risk, and the Phase 1 and Phase 2 groups should be read separately.

The record also reports participants affected by other, non-serious adverse events: 6 of 7 in Phase 1 Ampion, 19 of 20 in Phase 2 Ampion, and 16 of 20 in Phase 2 placebo. Those counts are a different adverse-event category from serious events. The most frequent serious-event terms listed are Post Procedural Haemorrhage, Eczema, and Embolic stroke, each shown as 5.0%. The registry record does not provide further event details in the information or specify which group each listed term represents.

Adverse-event counts alone do not establish that an event was caused by a study injection. The registry record does not report event-level timing, duration, outcome, or a detailed causal assessment. The small group counts also mean that the safety figures describe the events recorded in this study, rather than resolving the range of possible event frequencies in a broader population.

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

The posted primary results describe a more negative average change in WOMAC A Pain score in the Ampion arm than in the placebo arm. The recalculated difference is -0.56, and its confidence interval lies below zero. The registry reports a two-sided p-value of 0.02. Taken together, these are statistical evidence of a difference in average change in the posted primary comparison, under the analyses reported. The outcome definition assigns more negative changes to larger reductions in pain.

That statistical finding does not, on its own, establish the practical importance of the difference. The registry record does not report a threshold for a clinically important change. It also does not show how many participants experienced a particular degree of improvement, and group means cannot describe each participant’s result. The result should therefore be understood as a comparison of average scores, not a guarantee of an individual outcome.

The secondary knee-function comparison is less definitive statistically: its recalculated confidence interval includes zero, and the sponsor reports p = 0.25. This does not prove that the groups were the same. It means the posted secondary result does not clearly distinguish the average changes under the reported comparison. Because no multiplicity procedure is reported, the secondary result should be regarded as exploratory.

The study record identifies a randomized, double-masked, parallel design, but does not provide full details of randomization, masking, missing-data handling, or the original statistical plan. The primary timing is also inconsistent between the outcome description and timeframe. These reporting limits should be considered when interpreting the estimate. The results describe the participants and outcomes recorded in this trial; they do not establish effects in populations or settings not described in the registry record. They are not medical advice or a recommendation about treatment.

18. Why This Trial Matters Statistically

This trial is statistically interesting because it reports both a randomized Phase 2 comparison and an unadjusted recalculation based on posted group summaries. The primary estimate, its uncertainty, and the sponsor’s reported test can be read together rather than relying on a single p-value. The posted means and standard deviations also make clear that the group-level average should be interpreted alongside variation among participants.

The record illustrates why an outcome’s definition and timing are essential parts of statistical interpretation. The primary pain score is defined as change from baseline to 12 weeks, yet the timeframe field refers to baseline and 20 weeks. That unresolved discrepancy is not a statistical technicality: it affects what period the estimated difference is intended to represent. Reporting a clear, consistent endpoint definition is necessary for readers to understand and assess a result.

The contrast between the primary pain finding and the less conclusive secondary knee-function finding also highlights the role of multiplicity. A result on one outcome should not automatically be treated as confirmation across related outcomes, particularly when no adjustment or hierarchy is reported. Likewise, the planning illustrations help distinguish a study’s observed result from future design questions: their assumptions are explicit, but they are not evidence about the trial’s original sample-size planning.

Finally, the registry separates safety by phase, making clear that Phase 1 and Phase 2 counts represent different groups and contexts. The record’s limited detail on event descriptions, missing data, and analysis procedures also shows why outcome summaries should be accompanied by transparent reporting of methods. These features make the trial useful for considering how estimates, uncertainty, endpoint definitions, and reporting completeness work together in clinical research interpretation.

19. 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 primary endpoint timing is inconsistent in the registry: its timeframe says scores were assessed at baseline and 20 weeks, while its description says the change was from baseline to 12 weeks. The record does not identify which timing applies to the posted primary result. This makes it harder to place the estimate in a clear follow-up context.

The registry identifies the primary analysis population as ITT but does not explain how that population was formed or how missing observations were handled. Detailed participant flow, reasons for missing outcome data, and sensitivity analyses are not reported in the registry record. These omissions limit assessment of whether incomplete data could have influenced the group comparisons.

The reported analyses are described as two-sided t-tests, but the registry does not provide a full statistical analysis plan, the sponsor’s confidence intervals, or further details about analysis implementation. The sponsor and recalculated p-values differ, and the registry record does not explain why. The recalculations use posted summary statistics and cannot address analytic details that are not represented in those summaries.

The registry lists three outcome measures and two analyses, but one secondary outcome is posted. It does not report whether multiplicity was addressed or how the outcomes were prioritized. It also does not report a clinically important difference threshold for the pain scale, limiting interpretation of the size of the estimated difference in practical terms.

Finally, the registry provides limited detail about the randomization and masking procedures, participant characteristics, event-level safety information, and the rationale for the overall enrollment. These matters are not reported in the registry record. The listed group results should therefore be interpreted as the posted trial evidence, with those reporting gaps in view.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Evaluate Safety of Three Intra-articular Injections of Ampion in the Knee of Adults With Osteoarthritis Pain — NCT02184156.
• Registry record last updated 2022-09-30; status last verified 2022-08.
• Results first posted 2022-09-30.
• 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.

23. Record Summary

The registry record describes a completed, randomized, double-masked, parallel-group Phase 1/2 study of three intra-articular injections of Ampion, compared with placebo in Phase 2, for adults with pain due to knee osteoarthritis. The overall enrollment is listed as 47. The primary Phase 2 outcome is mean change in WOMAC A Pain score, with negative values defined as a decrease in pain. Its timing is described inconsistently in the registry.

The posted primary comparison has mean changes of -1.41 for Ampion and -0.85 for placebo. The registry reports a two-sided t-test with p = 0.02; the unadjusted recalculation gives a mean difference of -0.56 and p = 0.015. The secondary knee-function result is less conclusive statistically, and no multiplicity adjustment is reported. Safety counts are listed separately for Phase 1 and Phase 2. Missing-data methods, the original sample-size justification, and a full statistical plan are not reported in the registry record.