Persica 002 Phase 1b PP353 vs Placebo in the Treatment of Low Back Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Persica 002 Phase 1b PP353 vs Placebo in the Treatment of Low Back Pain (NCT04238676), a randomized phase 1, phase 2 study. The primary outcome is Incidence of Adverse Events.

2. Clinical Question

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group study of PP353 and placebo. Its title identifies the study as Phase 1b, while the registry phase listing includes PHASE1 and PHASE2. Enrollment is recorded as 43, and the study status is completed. The registry lists Persica Pharmaceuticals Ltd as sponsor.

The stated study population had chronic low back pain associated with vertebral body endplate bone oedema (Modic 1). The brief description says the study investigated PP353 compared with placebo. The posted primary outcome is incidence of adverse events, with a timeframe of 0 to 12 months. The primary outcome population is described as the Full Analysis Set: enrolled subjects who received at least one dose of PP353 or placebo and had a valid post-baseline measurement for at least one efficacy variable.

The primary outcome results list a Part A PP353 group with 3 participants, a PP353 group with 20, and a placebo group with 20. The primary comparison is between PP353 and placebo; Part A is not part of that posted comparison. The record also lists disability outcomes at 12 months: change from baseline in Roland Morris Disability Questionnaire-23 and Oswestry Disability Index scores. Their posted group counts are 18 for PP353 and 19 for placebo.

The registry record does not report the original sample-size justification, the planned statistical analysis details, or whether interim analyses were planned. The arm descriptions are blank for PP353 and identify “Sham injection” for the other arm, despite the intervention and outcome listings referring to placebo. The registry record does not explain this labeling.

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: In Part A, 9 participants were screened, 3 of whom were included in the study. No summary analyses were conducted for efficacy in Part A. In Part B, 136 participants were screened, 40 of whom were randomised and met the criteria to be included in the Full Analysis Set (FAS).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) consisted of all enrolled subjects who received at least one dose of PP353 or placebo and had a valid post-baseline measurement for at least one efficacy variable.

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 Incidence of Adverse Events, measured over 0 to 12 months.

The primary endpoint is incidence of adverse events, expressed as the count of participants with an event. The timeframe is 0 to 12 months. Its description defines treatment-emergent adverse events as events not present before treatment began, or events already present that increased in intensity or frequency after treatment initiation. The description specifies “All causality” treatment-emergent adverse events, so the outcome is not restricted to events judged related to treatment.

Counting participants with an event gives a binary outcome for each participant: an event was recorded or it was not. This measure is used to describe the proportion of participants who experienced at least one event during the stated timeframe. It does not show how many events each affected participant experienced, how severe each event was, or whether events were judged treatment-related. Serious adverse events are reported separately in the registry record.

The posted primary outcome counts are 15 of 20 participants in the PP353 group and 18 of 20 in the placebo group. These counts describe the observed safety outcome in the groups. They do not establish that any difference was caused by treatment. The registry record’s primary outcome description defines the Full Analysis Set as enrolled subjects who received at least one dose of PP353 or placebo and had a valid post-baseline measurement for at least one efficacy variable. The record does not provide additional detail about how missing primary outcome measurements were handled.

7. Results Posted in the Registry

• PP353: 75.0% (15/20) versus 90.0% (18/20) on control; risk difference -15.0 percentage points (95% CI -38.1 to 8.1), risk ratio 0.83 (0.62–1.12); unadjusted two-proportion z-test p = 0.212.

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 From Baseline in Roland Morris Disability Questionnaire-23 Score

• 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 errors.
• Result:
  • PP353: mean -9.43 versus -5.54 on control; difference -3.89 (95% CI -7.56 to -0.22), standardized effect d = -0.68; z-test p = 0.038.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for PP353 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Oswestry Disability Index

• 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 errors.
• Result:
  • PP353: mean -16.91 versus -8.28 on control; difference -8.63 (95% CI -16.76 to -0.50), standardized effect d = -0.68; z-test p = 0.038.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for PP353 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry reports two secondary disability outcomes at 12 months: change from baseline in the Roland Morris Disability Questionnaire-23 and change from baseline in the Oswestry Disability Index. Their posted mixed-model analyses both estimate a larger reduction in the PP353 group than in the placebo group, and both reported confidence intervals reach or approach the no-difference value. The results therefore form a directionally similar pattern across the two measures, but the estimates remain uncertain.

These outcomes address disability and change from baseline, whereas the primary endpoint counts participants with treatment-emergent adverse events. They answer different questions and should not be collapsed into one result. The primary comparison does not establish a disability effect, and the secondary findings do not change the interpretation of the primary safety endpoint.

The registry record reports a total of 6 outcome measures and 5 analyses, but posts results for 3 secondary outcomes. The posted outcomes include a measure of clinically relevant improvement in RMDQ-23, but no result for that outcome appears in the available record. The reason for the absent result is not reported in the registry record.

Secondary outcomes are often interpreted with caution because testing multiple outcomes increases the chance that at least one result will appear notable by chance. The registry record does not report whether a multiplicity adjustment was used or which secondary outcomes were designated as confirmatory. Their p-values are therefore unadjusted as posted and carry less evidential weight than a prespecified, multiplicity-controlled primary analysis. The shared direction across the two posted disability measures may be informative, but it does not remove the uncertainty or the potential consequences of multiple testing.

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

• Change From Baseline in Roland Morris Disability Questionnaire-23 Score
• Clinically Relevant Improvement (≥30%) in RMDQ-23
• Change From Baseline in Oswestry Disability Index

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome: whether a participant had at least one treatment-emergent adverse event during the stated timeframe. For a binary outcome, a risk is the proportion of participants in a group who experienced the event. A risk difference compares the two risks by subtracting the comparator risk from the intervention risk. In this record, the reported risk difference is -0.15 for PP353 relative to placebo. A negative value indicates that the observed event risk was lower in the PP353 group in this comparison; it does not by itself show that treatment caused the difference.

A confidence interval describes the range of values reasonably compatible with the data under the method used. The primary risk-difference interval, from -0.381 to 0.081, includes zero. Zero represents no difference in the risks. The interval therefore includes both a possible lower event risk with PP353 and a possible higher event risk with PP353. Its width reflects limited precision. A p-value addresses how unusual data at least as incompatible with the no-difference hypothesis would be under that hypothesis and the analysis assumptions. The unadjusted p-value is 0.212. It should not be read as the probability that the null hypothesis is true, or as a measure of clinical importance.

The registry also reports a risk ratio and an odds ratio with confidence intervals. These are alternative ways to express a binary-outcome comparison. A risk ratio compares the risks directly, while an odds ratio compares the odds of an event. They can communicate the same underlying group counts on different scales; they do not constitute independent evidence. When event risks are common, an odds ratio can appear more extreme than a risk ratio, so the measure’s scale matters when interpreting a result.

The secondary disability analyses use least-squares means from mixed-model analyses. A least-squares mean is a model-based estimate of a group mean, rather than simply a raw arithmetic average. The reported mean difference compares the estimated changes between groups. The Roland Morris Disability Questionnaire-23 analysis reports a difference of -3.88 and the Oswestry Disability Index analysis reports -8.6. Each analysis has a confidence interval and p-value reported in the registry. These model-based results are distinct from simple unadjusted calculations using posted group summaries. The latter are approximate and do not capture all features of the mixed model.

A standard error describes the estimated sampling variability of an estimate. The registry lists standard errors for the group least-squares means. A standard error is not a measure of how widely individual participants’ scores vary; it describes precision of an estimated mean. The secondary summary-statistic recalculations use approximate standard deviations derived from the standard errors and group sizes. Because this conversion is approximate and does not reconstruct the original model, the recalculated intervals and p-values can differ from the posted mixed-model analyses.

The study is described as randomized, quadruple-masked, and parallel-group. Randomization is intended to reduce systematic differences between groups at allocation, while masking is intended to reduce the influence of knowledge of assigned treatment on behavior, assessment, and reporting. These design features do not eliminate uncertainty, missing data, or bias in every stage of a trial. The registry record does not explain the exact masking roles or allocation procedures.

The primary outcome counts are 15 of 20 for PP353 and 18 of 20 for placebo; the listed Part A PP353 group has 3 participants and is not in the primary comparison. The primary endpoint is a participant count, not a count of all adverse-event episodes. A participant with multiple events still contributes as a participant with an event in a participant-level incidence measure. The record does not provide event-level counts or enough detail to describe recurrence.

General statistical context: over-dispersion occurs when variability in count data is greater than a model assumes. It can make standard errors too small if the model does not account for that extra variability. The primary endpoint is reported as participants with an event, rather than as a repeated event count, and the registry does not report an over-dispersion model for it. No such modeling approach should be inferred from the posted results.

The registry reports an unadjusted primary comparison and mixed-model analyses for the secondary disability outcomes. It does not report a complete statistical analysis plan, details of any multiplicity adjustment, or an analysis of interim data. Those features cannot be reconstructed from the posted summary statistics.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.15, with a confidence interval from -0.381 to 0.081. Because the interval includes zero, the data do not pin down whether the underlying difference favors a lower or higher event risk in the PP353 group. The interval also spans effects that may differ meaningfully in magnitude. The point estimate alone should not be treated as a precise estimate of the underlying difference.

For the Roland Morris Disability Questionnaire-23, the registry’s mixed-model estimate is -3.88, with a 95% confidence interval from -7.69 to -0.07. For the Oswestry Disability Index, the estimate is -8.6, with a 95% confidence interval from -17.3 to -0.0. These intervals indicate uncertainty around the model-based mean differences. The endpoint scales differ, so the numerical estimates should not be directly compared with each other as if they measured the same quantity.

A confidence interval is not a guarantee that the true effect lies within its limits. It is a procedure that, under its assumptions, produces intervals that cover the underlying value at the stated rate over repeated applications. In practice, readers can use an interval to assess both the direction and the range of effects compatible with the data. The small group counts contributing to these analyses make precision an important consideration. The registry record does not report a clinical threshold for interpreting the disability-score differences, so their clinical importance cannot be determined from these results alone.

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

For planning based on 100% of the observed effect, the estimate is 100 participants per arm for 80% power and 133 participants per arm for 90% power. For planning based on 75% of the observed effect, the estimates are 163 participants per arm for 80% power and 217 participants per arm for 90% power. For planning based on 50% of the observed effect, the estimates are 330 participants per arm for 80% power and 441 participants per arm for 90% power.

In plain terms, 80% power means that, if the assumed effect and analysis conditions were correct, a study of the stated size would have an 80% chance of detecting an effect at the specified significance level. The 90% column describes a higher chance under the same planning assumptions, and therefore requires a larger planned group size. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants. These are prospective planning illustrations, not observed power for this completed trial.

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 = 0.900; treatment proportion p₁ = 0.750; average p̄ = 0.825.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5374 = 1.0532.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5268 = 0.4434.
4. n = (1.0532 + 0.4434)² / (-0.1500)² = 99.5, rounded up to 100 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 <- 0.9                          # control proportion
p1 <- 0.75                          # 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(4238676)
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 = 100 (80% power), 133 (90% power)
 75% of observed effect: n per arm = 163 (80% power), 217 (90% power)
 50% of observed effect: n per arm = 330 (80% power), 441 (90% power)
power.prop.test: 99.5 
Simulated power at n = 100 per arm: 0.814 (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 record identifies incidence of adverse events as the primary outcome and lists several secondary outcomes, including disability measures. It does not report a complete statistical analysis plan, the hierarchy in which outcomes were to be tested, or whether a correction for multiple comparisons was planned or applied. Without that information, the results cannot be classified confidently as confirmatory or exploratory beyond their registry labels.

Multiplicity matters when several outcomes or comparisons are tested. As the number of tests grows, the chance of at least one apparently unusual result under a no-effect situation can increase. An adjustment can help control that risk, but the appropriate approach depends on the planned testing strategy. The registry record does not report such an adjustment for the posted secondary p-values. Their values should therefore be treated as unadjusted evidence, not as proof that the stated thresholds account for testing across outcomes.

The primary outcome population is described as enrolled subjects who received at least one dose and had a valid post-baseline measurement for at least one efficacy variable. The record does not report detailed participant flow, outcome-specific missing-data counts, or the method used to handle missing primary safety measurements. The secondary analyses have different posted group counts from the primary endpoint, but the reason for the differences is not reported in the registry record. The record also does not explain whether missing data were assumed to be random or how sensitivity to missingness was assessed.

These omissions limit assessment of analysis-population consistency and the robustness of the results. They do not establish that an inappropriate method was used; they mean the registry record does not include enough detail to evaluate these aspects fully. Interim analyses and any associated decision rules are also not reported in the registry record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: encephalitis viral (nos) (5.0%).

The serious adverse event results list 0 of 20 participants in the PP353 group and 1 of 20 in the placebo group. The Part A PP353 group lists 0 of 3. These counts are distinct from the primary outcome counts, which cover all-causality treatment-emergent adverse events rather than only serious events. No deaths are listed for any of the three groups.

The registry lists “Encephalitis viral (NOS)” among the top serious adverse event terms, with 5.0%. The record does not identify the group associated with that term in the information posted, so it should not be assigned to a particular arm. The serious-event counts are small and cannot, on their own, provide a precise comparison of serious-event risks. A zero count in a group does not demonstrate that the risk is zero.

Serious adverse events and all treatment-emergent adverse events have different definitions and should not be combined. The counts describe what was recorded in the trial groups; they do not establish causation. The registry record does not provide further detail on event narratives or how seriousness and causality were adjudicated.

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

The posted primary result describes a lower observed incidence of treatment-emergent adverse events in the PP353 group than in the placebo group, with a risk difference of -0.15. Its confidence interval includes zero and extends in both directions around that value. The unadjusted p-value is 0.212. Together, these statistics indicate that the primary comparison is uncertain and does not provide strong evidence of a difference under the unadjusted analysis. They do not show that the groups are equivalent, and they do not establish that PP353 caused a lower event rate.

The study also reports model-based secondary results for two disability measures. Both estimates favor a larger reduction from baseline in the PP353 group, but they are secondary outcomes with unadjusted results, and the registry record does not report a multiplicity strategy. Their pattern may merit attention, but it is not a substitute for a larger, adequately planned confirmation or for complete reporting of analysis methods. The record does not provide a clinically meaningful threshold for interpreting these score changes.

The available results apply to the participants and outcome measurements recorded in this trial. The primary comparison includes 20 participants in each of the PP353 and placebo groups, while the secondary analyses list 18 and 19, respectively. The record’s enrollment is 43, with a separate Part A PP353 group in the primary results. These group-specific counts do not establish how representative participants were of the broader intended population.

Statistical significance is not the same as clinical importance, and a non-significant result is not proof of no effect. The confidence intervals describe uncertainty under their analysis assumptions, while the registry record’s limited information on missing data, multiplicity, and analysis planning constrains interpretation. These results alone cannot establish overall benefit or harm, nor can they support individual treatment decisions.

17. Why This Trial Matters Statistically

This trial illustrates why an endpoint’s meaning matters as much as its numerical result. The primary outcome counts participants with at least one treatment-emergent adverse event. It is a safety measure, not a direct measure of pain or disability. The secondary outcomes concern changes in disability scores and should be interpreted separately from the primary safety comparison.

The primary risk difference is accompanied by a confidence interval that includes zero and allows a range of possible effects. That illustrates how a point estimate can appear to favor one group while the available data remain compatible with no difference or an effect in the opposite direction. Reading the interval alongside the estimate and p-value gives a more complete account of uncertainty than focusing on a single statistic.

The secondary disability analyses offer a directionally similar pattern across two measures, but multiple testing and incomplete reporting of the analysis plan affect how much weight those findings can carry. Model-based analyses also cannot be reconstructed fully from group summaries alone. The small groups contributing to the comparisons make these issues especially relevant to precision and interpretation.

Finally, the registry record includes both observed results and planning illustrations based on an observed effect. Those planning calculations answer a prospective design question under stated assumptions; they do not describe the power of the completed trial. Keeping that distinction clear helps prevent retrospective planning figures from being mistaken for evidence that the trial was or was not adequately powered.

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.

The primary comparison has limited precision: its confidence interval spans values on both sides of no difference. The trial’s registry enrollment is 43, and the primary comparison lists 20 participants in each of the PP353 and placebo groups, with a separate Part A PP353 group. The available record does not establish whether every enrolled participant contributed to every endpoint or explain the differences between primary and secondary analysis counts.

The registry does not report detailed outcome-specific missingness, participant flow, or sensitivity analyses for missing data. It also does not report the original sample-size justification, a complete statistical analysis plan, a multiplicity adjustment for the secondary outcomes, or whether interim analyses were planned. These absences limit assessment of how closely the posted analyses followed a prespecified plan.

The registry lists “Sham injection” in an arm description while naming placebo in the intervention and outcome listings. It does not explain this discrepancy in terminology. The serious adverse event term “Encephalitis viral (NOS)” is listed with 5.0%, but the posted information does not identify its group. No group attribution should be inferred from that listing.

Only two secondary disability outcomes have posted analysis results in the record, although a clinically relevant improvement outcome is also listed. The reason that result is not posted is not reported. The registry also does not provide a clinical threshold for interpreting the disability-score differences. Together, these reporting gaps and the uncertainty in the estimates limit the strength and scope of conclusions from the trial results.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Persica 002 Phase 1b PP353 vs Placebo in the Treatment of Low Back Pain — NCT04238676.
• Registry record last updated 2026-03-27; status last verified 2026-02.
• Results first posted 2026-03-27.
• 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

The registry record describes a completed randomized, quadruple-masked, parallel-group study of PP353 and placebo for chronic low back pain associated with vertebral body endplate bone oedema (Modic 1). It lists enrollment of 43 and identifies incidence of adverse events from 0 to 12 months as the primary outcome.

The primary comparison records treatment-emergent adverse events in 15 of 20 participants in the PP353 group and 18 of 20 in the placebo group. The risk difference is -0.15, with a confidence interval from -0.381 to 0.081 and an unadjusted p-value of 0.212. Secondary 12-month disability analyses report mixed-model comparisons for the Roland Morris Disability Questionnaire-23 and Oswestry Disability Index.

The primary result is uncertain, and the secondary results require caution because they are unadjusted and the registry does not report a complete analysis plan or multiplicity approach. Missing-data handling and the reasons for differing analysis counts are also not reported in the registry record.