A Study of the Safety, Tolerability and Efficacy of Treatment With AP1189 in Early RA Patients With Active Joint Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Safety, Tolerability and Efficacy of Treatment With AP1189 in Early RA Patients With Active Joint Disease (NCT04004429), a randomized phase 2 study. The primary outcome is Change in Clinical Disease Activity Index (CDAI).

2. Clinical Question

This is a short-term comparison of two doses against placebo in a defined early-RA population. It is not a comparison of AP1189 against methotrexate: the registry summary says participants were to start methotrexate up-titration, but the stated randomized comparator was placebo. The primary endpoint therefore concerns a threshold transition in disease activity during the trial period, rather than long-term disease control or a comparison of treatment strategies. The registry record does not report additional eligibility details or the full rationale for the selected threshold.

3. Trial Design

This completed phase 2 study was randomized, triple-masked, parallel-group, multicenter, and placebo-controlled. Its official title describes a two-part study of four weeks of AP1189 treatment. The registry reports enrollment of 105 participants. The study population was described as newly diagnosed participants with severe active rheumatoid arthritis, defined in the summary as CDAI > 22, who were to start up-titration with methotrexate.

The three groups were 50 mg AP1189, 100 mg AP1189, and placebo. Each arm description specifies four weeks of daily treatment, administered as a suspension. The primary outcome analysis included 29 participants in the 50 mg group, 33 in the 100 mg group, and 30 in the placebo group. The record explicitly notes that the number analyzed differs from the overall number enrolled because participants who received rescue medication during treatment were excluded from the primary analyses. These analysis counts should not be treated as the full enrollment or as the safety-group sizes.

The primary outcome was a participant count for a change from severe to moderate CDAI activity after four weeks. ACR response was also recorded as a secondary outcome. The registry lists five outcome measures and three ACR response entries, but does not give distinct ACR response definitions in the material reported. The trial is marked completed. The registry record does not report details of the two-part structure, the randomization procedure, allocation concealment, the masking procedures, or the original sample-size justification. It also does not list inferential analyses under reported analyses. These omissions limit what can be concluded about the planned analysis beyond the posted outcome descriptions and group counts.

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: The number of participants analyzed differs from the overall number of participants. Participants that received rescue medication during the treatment period was excluded from the analyses.

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 in Clinical Disease Activity Index (CDAI), measured over 4 weeks.

The primary endpoint counts participants who moved from severe to moderate clinical disease activity after four weeks, compared with baseline. The registry defines severe activity as CDAI > 22 and moderate activity as CDAI <= 22. It reports counts of participants meeting this transition rather than a group mean change in the CDAI score. The outcome is therefore binary at the participant level: a participant either met the stated transition or did not.

CDAI is calculated as the sum of four components: the swollen 28-joint count, the tender 28-joint count, the patient global assessment, and the physician global assessment. The joint counts cover the specified shoulders, elbows, wrists, hand joints, and knees. The patient and physician global assessments each use a scale from 0 to 100, with 100 indicating maximal activity. This combination brings joint findings together with patient and clinician assessments rather than relying on a single measure.

In general, a threshold-based endpoint can make a clinically defined category transition easy to describe, while losing information about the extent of change within each category. Participants whose CDAI changes but remains on the same side of the threshold do not count as having made the reported transition. The registry record does not report a separate continuous CDAI analysis or the rationale for choosing this specific threshold as the primary endpoint. The endpoint describes a short-term category change; it does not, by itself, characterize the full course of rheumatoid arthritis or longer-term outcomes.

7. Results Posted in the Registry

• 50 mg AP1189: 62.1% (18/29) versus 40.0% (12/30) on control; risk difference 22.1 percentage points (95% CI -2.8 to 47.0), risk ratio 1.55 (0.92–2.62); unadjusted two-proportion z-test p = 0.090.
• 100 mg AP1189: 51.5% (17/33) versus 40.0% (12/30) on control; risk difference 11.5 percentage points (95% CI -12.9 to 36.0), risk ratio 1.29 (0.74–2.23); unadjusted two-proportion z-test p = 0.360.

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.

ACR (American College of Rheumatology) Response

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • 50 mg AP1189: 37.9% (11/29) versus 33.3% (10/30) on control; risk difference 4.6 percentage points (95% CI -19.8 to 29.0), risk ratio 1.14 (0.57–2.26); unadjusted two-proportion z-test p = 0.712.
  • 100 mg AP1189: 60.6% (20/33) versus 33.3% (10/30) on control; risk difference 27.3 percentage points (95% CI 3.6 to 51.0), risk ratio 1.82 (1.02–3.23); unadjusted two-proportion z-test p = 0.030.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 50 mg AP1189 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for 100 mg AP1189 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

ACR response is the secondary outcome listed in the registry at four weeks. The results do not follow a uniform pattern across the two AP1189 comparisons: the posted estimate for one dose differs more from placebo than the estimate for the other, and the uncertainty intervals also differ. This contrast is not the same as the primary CDAI threshold transition. ACR response is a separate outcome construct, and the record does not report distinct definitions for the repeated ACR entries or explain whether they represent different response criteria.

The secondary findings should be read alongside, but not substituted for, the primary result. The primary endpoint estimates are positive, with intervals that include zero; the secondary comparisons vary in their estimated size and precision. Such variation can arise when outcomes measure different aspects of response and when estimates are based on limited participant counts. It does not, by itself, establish that one dose has a reproducible advantage or that the secondary endpoint confirms the primary finding.

The secondary p-values are unadjusted, and the registry record does not report a multiplicity strategy. In general, evaluating several outcomes and comparisons increases the chance that at least one result appears notable by chance, particularly when no adjustment or hierarchy is specified. The secondary estimates can be useful for describing the pattern observed and for motivating future questions, but they carry less inferential weight than a clearly prespecified primary analysis with a documented plan. ACR results also do not resolve the uncertainties arising from rescue-medication exclusions or from the short follow-up period. The registry record does not report adjusted secondary analyses or further details that would support a stronger confirmatory interpretation.

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

• ACR (American College of Rheumatology) Response
• ACR (American College of Rheumatology) Response
• ACR (American College of Rheumatology) Response

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary because it records whether each participant crossed from the severe CDAI category at baseline to the moderate category after four weeks. The reported arm values are counts of participants meeting that definition, and the analysis denominator is the number analyzed in each group. In general, binary outcomes are commonly compared by expressing the event frequency in each group and then contrasting those frequencies. The registry presents risk differences for the AP1189-versus-placebo comparisons.

What does a risk difference express?

A risk difference is the difference between the observed event proportions in two groups. Here, the event is the stated CDAI category transition, and the comparison is each AP1189 group against placebo. A positive estimate indicates a higher observed proportion meeting the transition in the AP1189 group than in placebo, based on the posted counts. It is an absolute contrast, not a relative measure. The estimates are 0.221 for 50 mg and 0.115 for 100 mg. These are observed comparisons, not proof that the assigned treatment caused the difference.

Relative measures answer a different question. A risk ratio compares the event proportions as a ratio, while an odds ratio compares the odds of the event. The record also gives these measures and their intervals: for 50 mg, the risk ratio is 1.552 with an interval from 0.920 to 2.617, and the odds ratio is 2.455 with an interval from 0.862 to 6.993. For 100 mg, the risk ratio is 1.288 with an interval from 0.744 to 2.23, and the odds ratio is 1.594 with an interval from 0.586 to 4.331. Relative estimates can sound larger or smaller depending on the scale; interpretation should remain connected to the event counts and the risk difference.

How should confidence intervals be read?

In general, a confidence interval expresses uncertainty around an estimated effect under the assumptions of the method used to construct it. A narrower interval indicates greater precision; a wider interval indicates more uncertainty. If an interval for a risk difference includes zero, the values in that interval include no absolute difference. Both primary risk-difference intervals include zero. The registry record does not report the confidence level or the method used to calculate these intervals, so those details should not be inferred.

The p-values reported for the primary comparisons are unadjusted: 0.09 for 50 mg and 0.36 for 100 mg. A p-value describes how compatible the observed data are with a specified null hypothesis under the test assumptions; it is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. In general, p-values do not replace estimates and intervals. The registry record does not report the test method, any covariate adjustment, or an analysis plan that would establish whether these comparisons were prespecified.

What does the analysis population mean?

The primary outcome counts are 18 of 29, 17 of 33, and 12 of 30 for the 50 mg, 100 mg, and placebo groups, respectively. The registry states that participants who received rescue medication during treatment were excluded from these analyses, and that the number analyzed differs from overall enrollment. Excluding participants after randomization can affect how well the randomized groups remain comparable, depending on who is excluded and why. The record does not report the number excluded from each arm, the handling of missing outcome data, or an alternative analysis retaining those participants.

The reported analysis count is distinct from enrollment and from the numbers at risk in the adverse-event summaries. The record lists safety group sizes of 35, 36, and 34, whereas the primary endpoint denominators are 29, 33, and 30. Different analysis populations can be appropriate for different outcomes, but the registry record does not describe the population definition for each analysis beyond the rescue-medication exclusion for the primary endpoint.

What is and is not an inferential analysis?

The registry reports estimates, confidence intervals, and unadjusted p-values for the comparisons, but its reported-analyses listing is empty. The record therefore does not identify a fuller sponsor analysis, an adjusted model, or the statistical procedure behind the posted comparisons. The posted estimates should be read as comparisons based on the reported group counts, not as evidence that an unreported model was used. The discrepancy flag is false, so no conflicting sponsor result is identified in the record.

In general, randomization supports comparison by balancing groups on average, but interpretation also depends on the conduct of the trial and the analysis population. Triple masking and placebo control are features of the design; the registry does not describe the procedures used to maintain masking or the allocation sequence. The four-week endpoint and the rescue-medication exclusion are especially relevant when deciding how far to generalize the numerical comparisons. Statistical significance, precision, outcome definition, missing-data handling, and multiplicity all contribute to a careful reading; none can be settled by a point estimate alone.

11. Confidence Intervals and Precision

The primary risk-difference intervals are wide and include zero. For the 50 mg comparison, the estimate is 0.221, with an interval from -0.028 to 0.469. For the 100 mg comparison, the estimate is 0.115, with an interval from -0.129 to 0.360. In general, an interval shows a range of effect values compatible with the data under the calculation method. These intervals allow for both no difference and contrasts in either direction, so the point estimates should not be treated as precise descriptions of the underlying effect.

The record does not state the confidence level or the interval-construction method. Without that information, it is not appropriate to attach an unreported coverage level or make assumptions about whether the method was exact, approximate, or adjusted. The group counts also show that the primary comparisons use fewer participants than the overall enrollment, because rescue-medication recipients were excluded. The record does not give the number excluded by group or explain the effect of those exclusions on precision.

Secondary ACR comparisons have their own uncertainty intervals, and those should be considered separately from the primary endpoint. In general, a secondary estimate with an interval that excludes zero can still be uncertain, especially when several outcomes or comparisons are examined without a stated multiplicity approach. Precision is not the same as clinical importance: the registry record does not report a minimum important difference or a threshold for a meaningful risk difference. The intervals quantify uncertainty on the reported statistical scale, not the importance of an outcome to an individual participant.

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 sample-size figures are planning illustrations based on the observed effect, not the trial's original design calculations. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect. The original sample-size assumptions and justification are not reported in the registry record.

The figures are participants per arm for these binary outcomes, not total events. The 80% power column describes the planned number per arm for a design that would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and those assumptions were correct. The 90% power column describes the corresponding number per arm for a higher probability of detecting that same specified effect. These are prospective planning quantities, not evidence that the completed trial had a particular probability of detecting an effect.

Each row uses a different fraction of the observed effect: 100%, 75%, or 50%. Planning for a smaller effect requires more participants per arm than planning for a larger effect, because smaller differences are harder to distinguish from random variation. The figures are recalculations using the posted results and stated assumptions; they are not the trial's observed power. They should be treated as illustrations of how assumptions about the effect size influence planning, not as proof of adequacy or inadequacy of the original design. The registry record does not report whether the trial's initial sample-size calculation used these assumptions or another approach.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.400; treatment proportion p₁ = 0.621; average p̄ = 0.510.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7070 = 1.3856.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6895 = 0.5803.
4. n = (1.3856 + 0.5803)² / (0.2207)² = 79.4, rounded up to 80 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
p0 <- 0.4                          # control proportion
p1 <- 0.620689655172414                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4004429)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 80 (80% power), 106 (90% power)
 75% of observed effect: n per arm = 142 (80% power), 190 (90% power)
 50% of observed effect: n per arm = 319 (80% power), 426 (90% power)
power.prop.test: 79.4 
Simulated power at n = 80 per arm: 0.801 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary CDAI outcome and three ACR response entries, but it does not report a statistical analysis plan explaining how these outcomes were prioritized or how repeated comparisons were to be handled. The record identifies the CDAI transition as the primary outcome. It does not say whether the ACR entries correspond to distinct response thresholds, whether any secondary outcome was formally ordered, or whether a multiplicity adjustment was planned.

In general, when many outcomes or comparisons are tested, the chance of obtaining at least one apparently unusual result by chance can rise. Multiplicity methods can control that risk or define a testing hierarchy, but the appropriate approach depends on the prespecified objectives. Because no such approach is reported, the unadjusted secondary p-values should be interpreted cautiously and should not be treated as confirmatory evidence on their own. The primary comparison p-values are also reported as unadjusted; the registry record does not clarify whether they were the only primary tests intended by the protocol.

The primary outcome population excludes participants who received rescue medication during the treatment period. This is a stated analysis-population rule, but the record does not report the number excluded in each arm, the timing or reasons for rescue use, or the outcome status of excluded participants. It also does not describe other missing-data handling, such as imputation, sensitivity analyses, or an analysis based on all randomized participants. Those details matter because excluding participants after randomization can alter the composition of the groups being compared.

The record lists no reported analyses and does not provide the original sample-size assumptions, a prespecified model, or analysis details for the posted estimates. The absence of these details does not show that no plan existed; it means the plan is not reported in the registry record. Without that information, it is difficult to distinguish confirmatory tests from exploratory comparisons or to assess whether the posted analyses follow the original plan. These limitations apply to interpretation of both the primary and secondary results.

15. 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 non-serious adverse event terms

The adverse-event summaries list the numbers at risk as 35 for 50 mg AP1189, 36 for 100 mg AP1189, and 34 for placebo. The recorded number of participants affected by serious adverse events is 0 in each group. Deaths are also recorded as 0 in each group. These are counts in the registry record; they do not establish that an event is impossible or characterize risks beyond the participants and follow-up recorded in this study.

The summaries also report other adverse events affecting 14 participants in the 50 mg group, 16 in the 100 mg group, and 12 in the placebo group. Those counts are separate from the serious adverse-event counts. The registry record does not list serious-event terms, and it does not report event-level descriptions, severity, timing, duration, or attribution details in the posted summary. It therefore supports a descriptive reading of the recorded counts, not a detailed comparison of event types or causes.

The safety-group sizes differ from the primary-outcome analysis denominators. The registry record does not explain in detail how safety follow-up was defined or why the group sizes differ. These brief summaries should not be interpreted as a comprehensive assessment of safety or as a comparison adjusted for duration or exposure.

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

The registry record describes a randomized, placebo-controlled comparison of two AP1189 doses over four weeks in newly diagnosed participants with severe active rheumatoid arthritis. For the primary endpoint, the posted participant counts and risk differences provide a short-term comparison of the proportion meeting a specified CDAI category transition. Both point estimates favor a higher observed transition proportion in the AP1189 groups than in placebo, but both intervals include zero and extend across values in either direction. The results are therefore uncertain, rather than a precise estimate of the difference between groups.

The findings do not establish that AP1189 works or does not work. A point estimate is a summary of the observed data, and its interpretation depends on uncertainty, design, analysis populations, and the prespecified plan. The rescue-medication exclusion changes the primary outcome analysis population from overall enrollment, while the record does not describe the excluded participants or provide alternative analyses. The posted p-values are unadjusted, and the inferential analysis plan is not reported.

The study also does not answer whether the observed outcomes persist beyond four weeks, whether they apply to people outside the described early-RA population, or how AP1189 compares with other active treatments. The randomized comparator was placebo; the summary's mention of methotrexate up-titration does not make methotrexate the comparator. The registry does not report continuous CDAI change, long-term outcomes, or additional subgroup results in the material summarized.

Safety counts are descriptive and show no participants recorded with serious adverse events and no deaths in the listed groups, alongside counts for other adverse events. Those summaries cannot rule out uncommon events or determine comparative safety with precision. Overall, the record offers a snapshot of short-term outcomes and uncertainty, not a complete account of efficacy, safety, or longer-term clinical value.

17. Why This Trial Matters Statistically

This trial illustrates why a binary endpoint requires attention to its definition and analysis population. The primary result is not a mean reduction in CDAI; it is a count of participants crossing from the severe category to the moderate category. That distinction changes what the estimate represents. A participant can have a CDAI change without crossing the threshold, and that change would not be counted as the primary event under the registry definition.

The results also show why estimates should be read with their intervals. Both primary risk-difference intervals include zero and are broad, so the observed point estimates do not give a precise account of the underlying contrast. Reporting the event counts, absolute differences, and relative measures gives readers several ways to understand the observed comparisons, but those measures do not eliminate uncertainty or substitute for a documented analysis plan.

Another important statistical feature is the difference between the enrolled population and the primary analysis population. Participants who received rescue medication were excluded, and the registry notes that the numbers analyzed differ from overall enrollment. That rule has direct relevance to interpretation because the primary comparisons are based on the analyzed participants, not everyone enrolled. The record does not report enough detail to assess the consequences of that exclusion.

Finally, the secondary ACR results and safety counts need different kinds of interpretation. Unadjusted secondary comparisons raise multiplicity concerns, while adverse-event summaries are descriptive counts rather than detailed risk analyses. The registry leaves important methodological details unreported, including original sample-size assumptions, interval methods, and analysis plans. The trial is therefore useful as an example of how endpoint construction, precision, missing-data reporting, and multiplicity shape the meaning of posted clinical trial results.

18. 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 limitations affect how far the registry results can be interpreted. The primary outcome analysis excludes participants who received rescue medication during treatment, and the registry says that analysis counts differ from overall enrollment. The number excluded from each group and the outcomes among those participants are not reported in the registry record. Without that information, the effect of the exclusion on the group comparisons cannot be evaluated from the record.

The follow-up for the stated primary outcome is four weeks. The registry record does not report longer-term CDAI results or whether the observed category changes persisted. The endpoint uses a severe-to-moderate threshold transition, and the record does not report a continuous CDAI analysis to describe changes that did not cross the threshold. The available results therefore provide limited information about the amount and durability of change.

The registry lists repeated ACR response entries but does not provide separate definitions for them in the reported material. It also does not report a multiplicity plan, original sample-size justification, confidence-interval level or method, or detailed inferential analysis plan. These omissions limit assessment of which comparisons were confirmatory and how the estimates were calculated. The trial's two-part structure is named, but details of its parts are not reported in the registry record.

The adverse-event summary provides group counts but not detailed event descriptions, exposure-adjusted rates, or additional context for comparing event patterns. The record does not report detailed eligibility criteria, randomization procedures, or masking procedures. These are limits of the registry information and should not be taken as evidence that such procedures or analyses were absent from the trial itself.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of the Safety, Tolerability and Efficacy of Treatment With AP1189 in Early RA Patients With Active Joint Disease — NCT04004429.
• Registry record last updated 2024-07-10; status last verified 2024-07.
• Results first posted 2024-07-10.
• 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.

22. Record Summary

This completed phase 2 study randomized participants with early rheumatoid arthritis to 50 mg AP1189, 100 mg AP1189, or placebo for four weeks. It was described as multicenter, parallel-group, triple-masked, and placebo-controlled, with enrollment of 105. The primary outcome counted participants moving from severe to moderate CDAI activity. Its analyzed groups were 29, 33, and 30 participants, respectively; participants receiving rescue medication were excluded from these analyses.

The primary risk-difference estimates were 0.221 for 50 mg and 0.115 for 100 mg, with both confidence intervals including zero. ACR response was also recorded as a secondary outcome, and the registry listed adverse-event counts, including 0 serious adverse events and 0 deaths in each group. The original sample-size rationale, analysis plan, multiplicity approach, and several outcome-analysis details are not reported in the registry record.