Efficacy and Safety of Intravenous and Subcutaneous Secukinumab in Moderate to Severe Chronic Plaque-type Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Intravenous and Subcutaneous Secukinumab in Moderate to Severe Chronic Plaque-type Psoriasis (NCT01412944), a randomized phase 3 study. The primary outcome is Percentage of Participants (Who Achieved a Partial Response Defined as ≥ 50% But < 75% Improvement in Psoriasis Area and Severity Index (PASI) After 12 Weeks of Treatment in Study AIN457A2304) With 75% Improvement From Baseline in PASI.

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase 3 trial of secukinumab in moderate to severe chronic plaque-type psoriasis. The registry lists an enrollment of 43. The primary endpoint results are reported for 21 participants in each treatment group, using the analysis population described in the registry record. These enrollment and analysis figures should be kept distinct: the registry does not explain the difference between the total enrollment figure and the group counts used for this outcome.

The trial focused on people who had already received secukinumab and had a partial response in study AIN457A2304. The qualifying partial response was at least 50% but below 75% improvement in PASI after 12 weeks of treatment in that study. The current trial's primary endpoint was evaluated at week 8. The registry lists the trial status as completed, with a start of 2011-12 and primary completion of 2013-04.

During the intravenous period, one group received 10mg/kg AIN457 intravenously at randomization, week 2 and week 4, and subcutaneous placebo at randomization and week 4. The other group received two 150 mg subcutaneous AIN457 injections at randomization and week 4, and intravenous placebo at randomization, week 2 and week 4. The registry describes the dosing as double-dummy, so each group had active treatment by one route and placebo by the other during that period. During maintenance, both groups received open-label AIN457 300 mg subcutaneously.

The stated design supports a randomized comparison of the two initial regimens in this selected group of partial responders. The later maintenance period is described as open-label and uses the same subcutaneous dose in both groups; the registry record does not provide a randomized comparison for that maintenance treatment. Further details about randomization procedures, allocation concealment, treatment adherence, or the original design assumptions are not reported in the registry record.

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: Participants of the CAIN457A2304 150 mg or AIN457 300 mg treatment groups, who were partial responders at week 12 of CAIN457A2304, were randomized in a 1:1 ratio to the AIN457 300 mg s.c. or AIN457 10 mg/kg I.V. treatment groups of CAIN457A2307.

IV: Per Previous CAIN457A2304 Treatment

Reasons for not completing this period:

IV: Per CAIN457A2307

Reasons for not completing this period:

Entire: IV + Maintenance

Reasons for not completing this period:

Entire: IV + Maintenance

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The full analysis set (FAS) population was used for this analysis. The FAS included all participants to whom treatment was assigned. Only participants from the FAS, who had week 8 values, were included in the analysis.

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 Percentage of Participants (Who Achieved a Partial Response Defined as ≥ 50% But < 75% Improvement in Psoriasis Area and Severity Index (PASI) After 12 Weeks of Treatment in Study AIN457A2304) With 75% Improvement From Baseline in PASI, measured over Week 8.

The primary endpoint is the percentage of participants achieving at least 75% improvement from baseline in PASI at week 8. PASI combines the severity of psoriasis lesions and the area of affected skin into a score. The registry describes a scale from 0, indicating no disease, to 72, indicating maximal disease. It assesses the head, arms, trunk and legs separately, considering the estimated affected area and clinical signs including erythema, induration and desquamation.

A response threshold turns the continuous PASI score into a binary outcome for this endpoint: each participant either meets the specified improvement threshold or does not. Reporting the percentage meeting the threshold gives an interpretable summary of how many participants achieved a substantial change by the defined assessment time. It does not show the full distribution of individual PASI changes, and it does not describe how far above the threshold responding participants improved.

The endpoint is clinically interpretable because it combines affected area and lesion severity, rather than focusing on only one component. But interpretation depends on the stated population and time point. These participants had been selected for a partial response to secukinumab in an earlier study, and this outcome concerns week 8 in the current trial. The registry says that only participants in the full analysis set with week 8 values were included in the analysis. The exact handling of participants without week 8 values, and any additional endpoint conventions, are not reported in the registry record.

7. Results Posted in the Registry

• AIN457 I.V.: 90.5% (19/21) versus 66.7% (14/21) on control; risk difference 23.8 percentage points (95% CI 0.1 to 47.6), risk ratio 1.36 (0.97–1.89); unadjusted two-proportion z-test p = 0.060.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the percentage measure?

The primary endpoint is binary at the participant level. Each person is classified according to whether they achieved at least 75% improvement in PASI by week 8. The group percentage is the number meeting that criterion relative to the participants included in the outcome analysis. The registry reports the full analysis set as the population assigned to treatment, with only those who had week 8 values included in this particular analysis. Thus, the analysis description contains both an assigned-treatment population and a week 8 availability condition.

A binary endpoint is easy to interpret as a response proportion, but it discards detail within each category. It does not distinguish a participant who just crossed the threshold from one with a much larger PASI improvement. It also does not show the extent of improvement among those who did not cross the threshold. Other listed PASI outcomes could provide complementary views, but their numerical results are not reported in the registry record for this account.

How should the group comparison be understood?

The reported group percentages are 66.7% for subcutaneous treatment and 90.5% for intravenous treatment. The unadjusted recalculated risk difference is 0.238, with a confidence interval from 0.001 to 0.476. A risk difference expresses the contrast in response proportions on the proportion scale. A value above zero indicates a higher observed response proportion in the intravenous group. The estimate summarizes the observed contrast; its interval communicates the uncertainty around that estimate under the calculation's assumptions.

The unadjusted p-value is 0.06. A p-value describes how unusual data at least as incompatible with a null comparison would be under the assumptions of the specified test, if the null model were correct. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The registry record does not report the formal test method for a sponsor analysis. The interval and p-value have different threshold implications at 0.05, so neither should be treated as a definitive standalone verdict. The methods behind a sponsor-level comparison are not reported in the registry record.

What does randomization contribute?

Random allocation is intended to make the assigned groups comparable on average at the start of a study, including with respect to factors that were not measured. It supports interpreting between-group differences as related to assigned treatment, subject to issues such as chance imbalance, adherence, missing outcome data and the conduct of the trial. It does not ensure that two small groups will have identical baseline characteristics, nor does it eliminate uncertainty in the estimated treatment contrast.

The record identifies the study as randomized, parallel-group and quadruple-masked. It also describes a double-dummy approach during the intravenous period, with active treatment by one route and placebo by the other. The registry does not give details about the randomization sequence, allocation concealment, or which roles were included in quadruple masking. Those implementation details are not reported in the registry record.

Why does the analysis population matter?

The stated full analysis set includes all participants to whom treatment was assigned, but this primary endpoint analysis includes only members of that set with week 8 values. This means the outcome result is not described as including every assigned participant regardless of whether the week 8 measurement was available. The registry record does not state how many week 8 values were unavailable, why any were unavailable, or whether missing outcomes were imputed or otherwise handled. Those details matter because the observed response percentages could be affected if outcome availability is related to treatment or response.

The registry uses the term full analysis set, but the explicit endpoint description adds the week 8 values condition. Readers should retain that qualification rather than assume that every assigned participant contributed a measured outcome. The exact statistical approach for handling missing data is not reported in the registry record.

What role do secondary outcomes play?

The record lists secondary measures including PASI 50/75/90/100 responses, IGA 0 or 1 response, mean PASI change, IGA categories, DLQI outcomes, EQ-5D health-state assessment, anti-secukinumab antibodies, and response in relation to failed previous biologic therapy. These outcomes cover clinical response, quality of life, immunogenicity and a relationship with prior treatment history. The record lists 8 secondary outcomes and 10 outcome measures overall.

When several outcomes or thresholds are examined, the chance of at least one apparently unusual result can increase if each is tested separately at a conventional threshold. Statistical methods may address that issue through a prespecified hierarchy or adjustment, but such an approach cannot be assumed. Multiplicity procedures, endpoint hierarchy and the secondary outcome analysis methods are not reported in the registry record. The listed outcomes therefore provide context for the intended breadth of assessment, but do not establish which analyses were confirmatory or how results should be combined.

What can be said about precision and planning?

Confidence intervals are a way of expressing uncertainty around an estimate: they show a range of values compatible with the observed data under the calculation's assumptions. A wide interval indicates that the data are consistent with a broad range of effect sizes. The risk-difference interval is notably broad relative to its lower endpoint, so the observed contrast is not estimated with high precision. The trial's original sample-size justification and any interim analysis plan are not reported in the registry record.

A separate planning illustration uses the observed effect as a reference and considers smaller fractions of it. It assumes a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation. Those are assumptions for the illustration, not evidence of the original protocol's design choices. Planning numbers describe hypothetical future study sizes under stated assumptions. They are not observed power for this trial, and they do not change the uncertainty in the current results.

10. Confidence Intervals and Precision

The primary response proportions are 66.7% in the subcutaneous group and 90.5% in the intravenous group. The unadjusted recalculated risk difference is 0.238, with a confidence interval from 0.001 to 0.476. This interval indicates substantial uncertainty around the size of the group contrast. It extends from a value very close to no difference to a considerably larger positive difference, so the point estimate should not be read as a precisely established effect size.

A confidence interval is a range generated by a statistical procedure that, under its assumptions, reflects uncertainty in estimating a quantity from a sample. It is not a range containing a known fixed proportion of individual outcomes, nor is it a direct statement about the probability that the true difference lies inside this particular interval. Its interpretation also depends on the method used to construct it. The registry record does not report a sponsor-level interval method for the comparison.

The unadjusted p-value is 0.06, while the interval's lower endpoint is above zero. These summaries do not align at the 0.05 threshold if interpreted using the usual matching-test and matching-interval convention. The registry record does not describe enough about the methods to explain that difference. Consequently, the interval and p-value should be reported as they are, without forcing them into a single binary conclusion.

Precision is limited by the small endpoint groups, each of which contains 21 participants. Even a large observed percentage contrast can have a wide interval when the available data are limited. The interval is more informative than the point estimate alone because it shows that the plausible magnitude remains uncertain. It does not resolve questions about generalizability beyond partial responders, outcomes after week 8, or missing week 8 measurements.

11. 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 for a hypothetical comparison with equal allocation between two arms. They are participants per arm, not total events. The calculation assumes a two-sided significance level of 0.05 and a normal approximation. It uses the observed effect as a reference and considers planning for 100% of that effect, 75% of the observed effect, and 50% of the observed effect. These are planning assumptions, not the original trial's reported design justification; that justification is not reported in the registry record.

The 80% power column gives the number of participants per arm that the illustration estimates would be needed for an 80% chance of detecting the assumed effect, if the assumptions and effect size were correct. The 90% power column gives the corresponding planning number for a 90% chance. These percentages describe long-run properties of the hypothetical design under its assumptions; they are not probabilities that the observed trial result is true.

For planning based on 100% of the observed effect, the illustration gives 46 participants per arm for 80% power and 61 participants per arm for 90% power. Planning for 75% of the observed effect gives 90 participants per arm for 80% power and 120 participants per arm for 90% power. Planning for 50% of the observed effect gives 220 participants per arm for 80% power and 293 participants per arm for 90% power. The pattern reflects a general statistical principle: smaller effects are harder to distinguish from random variation, so detecting them with the same planned power requires more participants.

These calculations are not observed power. They are planning illustrations based on the observed effect, which is itself uncertain, and they do not show that the trial was designed using these assumptions. The original trial's sample-size assumptions, including any prespecified target effect or power, are not reported in the registry record.

12. 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 = 0.667; treatment proportion p₁ = 0.905; average p̄ = 0.786.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5803 = 1.1373.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5553 = 0.4674.
4. n = (1.1373 + 0.4674)² / (0.2381)² = 45.4, rounded up to 46 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 <- 0.666666666666667                          # control proportion
p1 <- 0.904761904761905                          # 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(1412944)
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 = 46 (80% power), 61 (90% power)
 75% of observed effect: n per arm = 90 (80% power), 120 (90% power)
 50% of observed effect: n per arm = 220 (80% power), 293 (90% power)
power.prop.test: 45.4 
Simulated power at n = 46 per arm: 0.820 (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.

13. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is one result among a broader set of outcomes. The registry lists 10 outcome measures, including 8 secondary outcomes. The secondary measures cover additional PASI response thresholds and mean change, investigator global assessment, quality of life measures, anti-secukinumab antibodies and the relationship between response and failed previous biologic psoriasis therapy. Examining multiple outcomes can increase the chance of finding an apparently notable result by chance when each is assessed separately.

Multiplicity can be addressed with prespecified procedures such as a testing hierarchy or adjustments to significance thresholds. The registry record does not report whether the study used such procedures, whether the primary endpoint was tested within a prespecified sequence, or how the secondary outcomes were to be interpreted. The record does not provide enough information to determine which comparisons were confirmatory rather than exploratory. Therefore, the primary outcome should be distinguished from the wider set of listed measures, and unreported multiplicity procedures should not be presumed.

The primary endpoint population is described as the full analysis set, defined as participants to whom treatment was assigned, restricted to those with week 8 values for this analysis. The registry record does not state how many participants lacked week 8 values, the reasons for missingness, or the methods used to handle missing observations. It also does not report sensitivity analyses that might assess how different assumptions about missing outcomes affect the result. This makes it difficult to assess whether the observed response percentages could be influenced by outcome availability.

The record does not describe any interim analyses, stopping boundaries, or a data-monitoring plan for the primary outcome. Such details are not reported in the registry record and cannot be inferred from the completed status. Nor are the original sample-size justification, the full statistical analysis plan, or detailed analysis methods reported. These omissions limit assessment of whether the analysis followed a prespecified plan and how the family of outcomes was managed.

Randomization and masking are listed, but implementation details are limited. The registry identifies quadruple masking and describes double-dummy administration in the intravenous period; it does not specify which participant, investigator or assessor roles were masked or when masking ended. These missing details do not negate the posted result, but they constrain a full appraisal of analysis populations, missing data, multiplicity and conduct.

14. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dermatitis allergic (7.1%).

The registry reports serious adverse event figures across distinct treatment periods and group labels. During the intravenous period, the listed groups have zero serious adverse events among the respective participants at risk: 15, 6, 14 and 8. For the entire period, one group, labeled AIN457 150 mg to AIN457 10 mg/kg intravenous, has 1 serious adverse event among 14 participants at risk. The other entire-period groups list zero serious adverse events among 15, 6 and 8 participants at risk. These are period-specific counts; the groups and periods should not be combined into a single total.

For follow-up, the listed groups have zero serious adverse events among 1, 0, 2 and 2 participants at risk. A group with zero participants at risk does not provide an opportunity to observe an event in that period. The registry also lists DERMATITIS ALLERGIC at 7.1% among the top serious terms. The record does not provide enough detail to connect that term to a particular period or to infer its relationship to the primary endpoint.

These figures count serious adverse events, not all adverse events. Separate other-adverse-event counts are listed in the registry, but they are not substitutes for serious-event counts. Deaths are not reported in the registry record. The safety figures are descriptive and should be read with their group labels, periods and at-risk counts intact; they do not establish comparative safety from these small groups alone.

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

The primary result describes the percentage meeting a specific PASI response threshold at week 8 among participants selected for a partial response to secukinumab in an earlier study. The observed percentage was higher in the intravenous group than in the subcutaneous group. The unadjusted recalculated risk difference and its interval add a quantitative comparison, but the interval is broad and the p-value is 0.06. Taken together, the data show a higher observed response proportion in the intravenous group, while leaving uncertainty about the size and precision of the contrast.

The result does not establish what would happen for people who had not previously received secukinumab, for those with a different response to prior treatment, or for people outside the trial's eligibility group. It also does not answer whether one route is preferable for an individual. The trial's selected population and specified regimens matter: conclusions should not be extended automatically to other doses, schedules or treatment settings.

The endpoint is a threshold response at one assessment time. It does not describe the full distribution of PASI changes, the durability of response, or the quality-of-life outcomes listed as secondary measures. The registry describes open-label subcutaneous maintenance for both groups, but the primary result is at week 8 and does not supply a later randomized comparison of the original routes. Numerical results for the listed secondary outcomes are not reported in the registry record in the registry record used for this analysis.

The comparison also does not settle the uncertainty around missing week 8 values, because the registry does not state how many values were unavailable or how they were handled. The limited group sizes and broad confidence interval mean that the numerical difference should not be treated as a precise estimate. The statistical evidence is not a statement about an individual's expected response, and it does not support medical advice. It is a record of group-level results under the trial's stated conditions.

16. Why This Trial Matters Statistically

Statistically, this trial is notable for asking a focused question in a population defined by prior response. The participants were partial responders to secukinumab in study AIN457A2304, and the current endpoint asked whether they achieved at least 75% PASI improvement at week 8. This makes the interpretation population-specific: the comparison is about two routes and schedules in people selected by their earlier response, rather than a broad comparison across all psoriasis treatment settings.

The double-dummy design is also relevant. During the intravenous period, active treatment was administered by one route and placebo by the other, while masking is listed as quadruple. This design feature is intended to support masking despite different administration routes. The registry record does not describe the operational details of masking, so the extent to which each role remained masked cannot be assessed from the recorded information.

The trial also illustrates why point estimates, uncertainty intervals and p-values should be read together. The observed response percentages differ, but the unadjusted recalculated risk-difference interval is broad and the p-value is 0.06. The result is neither well described by the point estimate alone nor reduced to a yes-or-no conclusion based on a single threshold. The modest endpoint group sizes are important to that precision.

Finally, the registry lists several additional outcomes, including quality of life and immunogenicity, but numerical results and multiplicity methods are not reported in the record available for this analysis. This gap matters statistically because a primary outcome sits within a wider measurement program, and interpretation of multiple outcomes depends on prespecification and analysis methods. The example highlights how trial design, selected populations, endpoint timing, uncertainty and completeness of reporting jointly shape what can be concluded.

17. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint analysis includes only full-analysis-set participants with week 8 values. The registry does not report how many assigned participants lacked those values, why they were unavailable, or how missing outcomes were handled. Without that information, the effect of outcome availability on the reported percentages cannot be assessed. The record also does not describe sensitivity analyses for missing data.

The reported endpoint groups each contain 21 participants, and the registry's total enrollment is 43. The record does not explain the relation between the enrollment figure and the endpoint group counts. The comparison interval is broad, so the observed risk difference is not a precise estimate. The sample-size illustration is based on the observed effect and does not document the trial's original design justification.

The population is restricted to people with moderate to severe chronic plaque-type psoriasis who were partial responders after earlier secukinumab treatment. This limits direct generalization to people with other treatment histories or response patterns. The primary endpoint is measured at week 8, so it does not establish longer-term comparative results. Both groups received open-label AIN457 300 mg subcutaneously during maintenance, and the record does not report a later randomized comparison of the initial routes.

The registry lists secondary measures, but their numerical results and the handling of multiplicity are not reported in the registry record. The formal methods behind a sponsor-level comparison, the full statistical analysis plan, original sample-size assumptions, interim analyses and detailed masking procedures are also not reported. Safety figures are divided by treatment period and group, with small at-risk counts; they should not be collapsed into an overall comparative safety claim. These constraints limit the breadth and precision of interpretation from the posted results.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy and Safety of Intravenous and Subcutaneous Secukinumab in Moderate to Severe Chronic Plaque-type Psoriasis — NCT01412944.
• Registry record last updated 2015-03-18; status last verified 2015-03.
• Results first posted 2015-03-18.
• 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.

21. Record Summary

NCT01412944 is a completed randomized, quadruple-masked, parallel-group phase 3 trial sponsored by Novartis Pharmaceuticals. It enrolled participants with moderate to severe chronic plaque-type psoriasis who had been partial responders to secukinumab in an earlier study. The trial compared an intravenous AIN457 10mg/kg regimen with a subcutaneous AIN457 150 mg regimen during the intravenous period; both groups received open-label AIN457 300 mg subcutaneously during maintenance.

The primary outcome was the percentage achieving at least 75% improvement in PASI at week 8. The registry reports 66.7% for the subcutaneous group and 90.5% for the intravenous group, with 21 participants in each endpoint group. The unadjusted recalculated risk difference is 0.238, with a confidence interval from 0.001 to 0.476 and p = 0.06. These results indicate a higher observed response proportion in the intravenous group, with uncertainty about the size of the difference. Missing-data handling, multiplicity procedures, the original sample-size justification and full analysis methods are not reported in the registry record.