Efficacy and Safety of Clesrovimab (MK-1654) in Infants (MK-1654-004): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Clesrovimab (MK-1654) in Infants (MK-1654-004) (NCT04767373), a randomized phase 2, phase 3 study. The primary outcome is RSV Season 1: Number of Participants With Respiratory Syncytial Virus (RSV)-Associated Medically Attended Lower Respiratory Infection (MALRI).

2. Clinical Question

The question concerns a defined clinical event rather than all RSV infections. The endpoint required respiratory symptoms and signs assessed in a clinical setting, together with an RSV-positive nasopharyngeal sample by reverse transcriptase polymerase chain reaction. Outpatient and inpatient cases were combined for the Season 1 primary endpoint. The registry describes the study’s hypothesis as a reduction in this event with clesrovimab compared with placebo.

The comparison is between randomized groups, but the primary analysis population was further limited to participants who received a dose and were protocol compliant. The registry record does not report additional details about how protocol compliance was determined or how participants with missing endpoint information were handled.

3. Trial Design

This was a randomized, double-blind, parallel-group, placebo-controlled Phase 2b/3 study sponsored by Merck Sharp & Dohme LLC. The registry lists 3632 participants as enrolled. The study began on 2021-04-07, reached primary completion on 2024-07-09, and is recorded as completed.

Participants in the clesrovimab arm received one 105 mg intramuscular dose on Day 1; participants in the comparator arm received a single intramuscular placebo dose on Day 1. The registry says an eligible subset from RSV Season 1 would enter RSV Season 2. The Season 1 primary efficacy results use analysis denominators of 2398 for clesrovimab and 1201 for placebo. Those denominators are not the same as the total enrollment and should be read as the posted group sizes for this endpoint, not as the enrollment total.

The primary endpoint covers RSV Season 1 from Day 1 postdose through Day 150. The analysis population is described as all randomized participants who received a dose of study treatment and were protocol compliant. The registry also posts a safety population for RSV Season 1 with 2409 participants at risk in the clesrovimab group and 1202 in the placebo group. The different denominators reflect the populations used for the respective posted results; the record does not give further detail about their construction.

The registry lists 10 outcome measures and 8 analyses. It also reports two secondary outcomes for RSV Season 1: RSV-associated hospitalization and RSV-associated MALRI. Specific details of the original sample-size justification, the planned statistical analysis protocol, and any interim analyses 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: Per protocol, participants received one dose of study treatment on Day 1 during RSV Season 1. Participants did not receive study treatment during RSV Season 2. Study disposition data were not collected separately for RSV season 1 and RSV Season 2.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received a dose of study treatment and were protocol compliant.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All randomized participants

6. Primary Endpoint

The registry lists the primary outcome as RSV Season 1: Number of Participants With Respiratory Syncytial Virus (RSV)-Associated Medically Attended Lower Respiratory Infection (MALRI), measured over From Day 1 (postdose) to Day 150.

The primary endpoint is the number of participants with RSV-associated medically attended lower respiratory infection (MALRI) during RSV Season 1, from Day 1 postdose to Day 150. It is a binary participant-level outcome: each participant is counted according to whether the defined event occurred, rather than according to the number of episodes or the duration of illness.

For a case to meet the registry definition, the participant had to have cough or difficulty breathing in a clinical setting; at least one listed sign or symptom, such as wheezing, chest wall in-drawing or retraction, rales or crackles, hypoxemia, tachypnea, or dehydration due to respiratory symptoms; and an RSV-positive nasopharyngeal sample by reverse transcriptase polymerase chain reaction. Outpatient and inpatient RSV-associated MALRI cases were reported together for Season 1.

This endpoint focuses on medically attended lower respiratory illness associated with laboratory-confirmed RSV, rather than any infection detected without lower respiratory symptoms or signs. It is used to compare the occurrence of a clinically defined event between the randomized groups over a specified follow-up period. The endpoint description does not report separate primary counts for outpatient and inpatient cases.

7. Results Posted in the Registry

• RSV Season 1: Clesrovimab 105 mg: 2.5% (60/2398) versus 6.2% (74/1201) on control; risk difference -3.7 percentage points (95% CI -5.2 to -2.2), risk ratio 0.41 (0.29–0.57); unadjusted two-proportion z-test p = <0.001.

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.

RSV Season 1: Number of Participants With RSV-Associated Hospitalization

• 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:
  • RSV Season 1: Clesrovimab 105 mg: 0.4% (9/2398) versus 2.3% (28/1201) on control; risk difference -2.0 percentage points (95% CI -2.8 to -1.1), risk ratio 0.16 (0.08–0.34); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for RSV Season 1: Clesrovimab 105 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

RSV Season 1: Number of Participants With RSV-Associated MALRI

• 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:
  • RSV Season 1: Clesrovimab 105 mg: 2.7% (64/2398) versus 6.4% (77/1201) on control; risk difference -3.7 percentage points (95% CI -5.3 to -2.2), risk ratio 0.42 (0.30–0.58); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for RSV Season 1: Clesrovimab 105 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The two posted secondary outcomes cover RSV-associated hospitalization and RSV-associated MALRI in RSV Season 1. For both outcomes, the posted comparisons favor a lower observed event proportion in the clesrovimab group, and both recalculated unadjusted comparisons report p < 0.001. The registry also reports efficacy estimates for these outcomes, with a 95% confidence interval for each. These results are directionally consistent with the primary endpoint’s posted comparison.

The secondary outcomes add information about other clinically relevant expressions of RSV-associated illness, but they are not substitutes for the primary endpoint. Hospitalization is a distinct outcome, and the MALRI secondary outcome is listed with a follow-up period through Day 180, whereas the primary endpoint covers Day 1 to Day 150. Differences in definitions and follow-up windows mean that their estimates should not be treated as repetitions of the primary result.

The secondary comparisons carry less inferential weight when no adjustment for multiple testing is reported. Examining several outcomes creates more opportunities for apparently strong findings to occur by chance. The registry record does not report a multiplicity procedure, a testing hierarchy, or an adjustment to the secondary p-values. Accordingly, the unadjusted results are best read as supportive descriptions of the overall pattern, rather than as independent confirmatory evidence.

The record lists two secondary outcomes and posts analyses for both. It does not report further details about whether the outcomes were prespecified in a hierarchy, how missing observations were treated, or whether any additional multiplicity strategy was used. The coherent direction across endpoints is informative as a pattern, but it does not remove those uncertainties or establish that every secondary comparison was independently confirmatory.

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

• RSV Season 1: Number of Participants With RSV-Associated Hospitalization
• RSV Season 1: Number of Participants With RSV-Associated MALRI

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a binary count: the registry reports how many participants in each group experienced RSV-associated MALRI during the specified follow-up. For this type of outcome, the event count is interpreted against the number of participants in the relevant group. The posted primary counts are 60 events among 2398 clesrovimab participants and 74 among 1201 placebo participants.

What does the risk difference describe?

The risk difference compares the event proportions by subtracting the placebo-group proportion from the clesrovimab-group proportion. A value below zero means that the observed proportion was lower in the clesrovimab group. The recalculated primary risk difference is -0.037, with a 95% confidence interval from -0.052 to -0.022. This is an absolute measure: it expresses the gap between group proportions, rather than a ratio of one group’s proportion to the other.

Other comparative measures can describe the same binary outcome on a relative scale. For example, a risk ratio compares the two proportions as a ratio, while an odds ratio compares event odds. These measures answer related but not identical questions, and their values are not interchangeable with an absolute risk difference. The posted primary results include the risk difference, risk ratio, and odds ratio calculations; the interpretation in this analysis emphasizes the risk difference because it directly describes the absolute group contrast.

What does a confidence interval mean?

A confidence interval describes uncertainty in an estimated quantity under the method’s assumptions. In general, a 95% confidence interval is produced by a procedure that would cover the underlying quantity in 95% of repeated applications under the same assumptions. It is not a statement that 95% of individual outcomes fall within the interval, nor does it mean that every value within the interval is equally plausible. For the recalculated risk difference, the interval is entirely below zero. The registry-reported efficacy estimate also has a 95% confidence interval, from 44.1 to 71.9.

Why are two analyses reported?

The registry reports an efficacy estimate using an exact method, with a value of 60.4, a 95% confidence interval from 44.1 to 71.9, and p < 0.001. Separately, the posted group counts allow a simple unadjusted comparison of proportions. Its risk difference is -0.037, with a 95% confidence interval from -0.052 to -0.022 and unadjusted p < 0.001. The latter is labeled a recalculation because it is derived from the posted summary counts without adjustment. The record does not report enough detail to identify all features of the sponsor’s efficacy method, so these analyses should be kept distinct.

A p-value quantifies how unusual results at least as extreme as those observed would be under a specified null model, assuming the analysis assumptions hold. It is not an effect size, a measure of precision, or the probability that the treatment is ineffective. The p-values reported for these primary comparisons are less than 0.001. Their interpretation does not eliminate the need to consider the size of the estimated difference, its interval, the endpoint definition, and the analysis population.

What does “over-dispersion” mean for this outcome?

Over-dispersion is a general issue for outcomes modeled as counts when their variability exceeds what the assumed count distribution allows. It can make standard errors too small if ignored. The primary endpoint is posted as a count of participants with an event, a binary outcome, rather than a repeated-event count for each participant. The registry record does not report an over-dispersion parameter for this endpoint.

These calculations are summaries of group-level data, not individual-level modeling. They do not adjust for covariates, and no covariate-adjusted result is reported in the registry record. The stated analysis population and time window matter: these results concern the participants included in the primary analysis and events meeting the specific RSV-associated MALRI definition during the stated period.

11. Confidence Intervals and Precision

The primary efficacy estimate reported by the registry is 60.4, with a 95% confidence interval from 44.1 to 71.9. The interval communicates uncertainty around that estimate under the registry-reported exact method. Because the record does not give a further description of the measure’s construction, it is best interpreted as the posted efficacy estimate rather than re-labeled as an absolute or relative effect.

The recalculated, unadjusted risk difference is -0.037, with a 95% confidence interval from -0.052 to -0.022. This interval expresses uncertainty in the absolute difference between the two posted event proportions. It lies below zero, in the direction of fewer observed events in the clesrovimab group. Its width reflects that the estimate is not exact; a point estimate alone would conceal that uncertainty. The interval does not account for limitations that are not captured by the calculation, such as unreported missing-data handling or possible departures from the analysis assumptions.

The registry-reported estimate and the recalculated risk difference use different scales and methods. Their numerical intervals therefore should not be compared as if they measured the same quantity. The p-value of <0.001 for each reported primary analysis does not replace the confidence intervals: a p-value addresses compatibility with a null comparison, while an interval shows the range of effect estimates compatible with the respective method.

Precision is also shaped by the observed event counts and the analysis denominators. The registry does not report a separate precision analysis or additional uncertainty measures beyond the posted confidence intervals. Interpretation should focus on the endpoint and analysis population actually reported, rather than extrapolating these intervals to other populations, time periods, or definitions of RSV-related illness.

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 planning figures are for a binary outcome and are expressed as participants per arm, not total events. The illustration uses the primary observed effect as its reference and considers planning for 100%, 75%, or 50% of that observed effect. Under these assumptions, the primary endpoint figures are 485 participants per arm for 80% power and 649 participants per arm for 90% power when planning for 100% of the observed effect; 950 and 1,271 participants per arm for 75%; and 2,330 and 3,119 participants per arm for 50%.

These are planning illustrations computed from 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. The original trial’s sample-size assumptions and justification are not reported in the registry record.

In plain terms, the 80% power column gives the estimated number of participants needed in each arm for a design to have an 80% chance of detecting the specified effect under the planning assumptions, if that effect is real. The 90% column uses a higher target chance of detection and therefore gives larger participant requirements for the same effect. Planning for a smaller effect requires more participants because a smaller separation between groups is harder to distinguish from random variation.

These figures are not observed power. They are prospective illustrations based on the observed effect and stated assumptions, not a measure of how much power the completed trial actually had.

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 = 0.062; treatment proportion p₁ = 0.025; average p̄ = 0.043.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.2879 = 0.5643.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.2867 = 0.2413.
4. n = (0.5643 + 0.2413)² / (-0.0366)² = 484.6, rounded up to 485 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 <- 0.0616153205661948                          # control proportion
p1 <- 0.0250208507089241                          # 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(4767373)
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 = 485 (80% power), 649 (90% power)
 75% of observed effect: n per arm = 950 (80% power), 1,271 (90% power)
 50% of observed effect: n per arm = 2,330 (80% power), 3,119 (90% power)
power.prop.test: 484.6 
Simulated power at n = 485 per arm: 0.812 (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. Analyses Reported by the Sponsor

The registry-reported primary analysis gives an efficacy estimate of 60.4, with a 95% confidence interval from 44.1 to 71.9, using an exact method; the reported p-value is <0.001. The simple unadjusted recalculation from the posted counts gives a risk difference of -0.037, with a 95% confidence interval from -0.052 to -0.022 and p < 0.001.

These are not competing versions of one identical statistic. The registry-reported efficacy estimate is the sponsor-reported analysis recorded for the outcome, while the recalculation is an unadjusted absolute difference derived from the event counts and denominators. Different measures and methods can yield different numerical values even when they summarize the same group comparison. The registry record does not describe enough detail to reconstruct every feature of the efficacy analysis.

The recalculation is useful as a transparent check of the group counts on an absolute scale, but it does not supersede the registry-reported analysis. The posted record does not identify a discrepancy between the results. Both analyses indicate a lower observed event proportion in the clesrovimab group, and both report p < 0.001. Their estimates and confidence intervals should nevertheless be interpreted on their respective scales.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when statistical tests are conducted across several outcomes, time points, subgroups, or other comparisons. Even when each test uses a conventional threshold, the chance of at least one false-positive result can increase as more tests are considered. The registry lists 10 outcome measures and 8 analyses, including two posted secondary outcomes. It does not report a multiplicity adjustment, a testing hierarchy, or a family-wise error strategy. The primary result and the secondary results should therefore be distinguished, and the unadjusted secondary p-values should be interpreted cautiously.

The registry identifies the primary analysis population as randomized participants who received a dose and were protocol compliant. It does not report how protocol compliance was defined, whether any participants were excluded after randomization, or the exact number excluded for each reason. It also does not describe how missing endpoint information was handled, whether imputation was used, or whether sensitivity analyses addressed missing data. These details are not reported in the registry record.

Missing data can affect a binary outcome comparison if participants without observed endpoint status differ from those whose outcomes are known. The impact depends on the amount, pattern, and handling of missing information. Without those details, the posted group counts and confidence intervals can be described as reported, but the possible influence of missingness cannot be assessed from the registry record alone.

The record names an exact method for the reported primary efficacy analysis but does not report the full statistical analysis plan, all model specifications, or any interim-analysis procedures. It is therefore not possible to infer whether other planned analyses or adjustments were undertaken. The posted results should be interpreted according to the stated endpoint, population, and methods, with unreported analysis details treated as unknown rather than assumed.

16. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.5%), bronchiolitis (1.6%), respiratory syncytial virus bronchiolitis (1.1%), gastroenteritis (0.8%), pneumonia respiratory syncytial viral (0.7%).

For RSV Season 1, the registry reports serious adverse events in 282 of 2409 participants at risk in the clesrovimab group and 151 of 1202 in the placebo group. The listed percentages for the most frequent serious-event terms include pneumonia at 2.5%, bronchiolitis at 1.6%, RSV bronchiolitis at 1.1%, gastroenteritis at 0.8%, pneumonia respiratory syncytial viral at 0.7%, and bronchitis at 0.7%. These term frequencies describe recorded serious adverse events; they are not treatment-effect estimates.

Other adverse events were reported for 1432 of 2409 participants at risk in the Season 1 clesrovimab group and 724 of 1202 in the Season 1 placebo group. The record lists 7 deaths in the Season 1 clesrovimab group and 3 in the Season 1 placebo group. It does not provide information in these figures about cause, timing, or attribution, so the counts alone do not establish whether an event was caused by study treatment.

For the eligible subset entering RSV Season 2, serious adverse events were reported for 32 of 1017 clesrovimab participants and 20 of 501 placebo participants; no other adverse-event denominator or count is posted for that season in these results. Season 2 involved a subset from Season 1, so its risk sets should not be treated as independent of the earlier season. These summaries are descriptive and do not, by themselves, establish comparative safety.

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

The posted data show that fewer participants in the clesrovimab group than in the placebo group met the defined RSV-associated MALRI endpoint during RSV Season 1, within the stated primary analysis population and follow-up period. The registry-reported efficacy estimate is 60.4, with a 95% confidence interval from 44.1 to 71.9. The unadjusted recalculation of the absolute difference is -0.037, with a 95% confidence interval from -0.052 to -0.022. These summaries describe the observed trial comparison and its statistical uncertainty.

The result does not describe every RSV infection or every respiratory illness. It concerns an event requiring the specified symptoms and signs in a clinical setting and a positive RSV test, with outpatient and inpatient cases combined. Nor does it cover time beyond the stated primary follow-up period. The secondary MALRI analysis uses a different follow-up window, and the hospitalization endpoint is a distinct outcome.

The comparison does not establish that the same effect would occur in populations outside the healthy pre-term and full-term infants studied, or under different care settings and follow-up conditions. The registry record does not report enough detail about missing data, the complete statistical plan, or multiplicity handling to resolve all methodological uncertainties. The posted p-value is not a measure of clinical importance and is not the probability that a treatment effect is absent.

Safety counts also require careful interpretation. Serious adverse events and deaths are recorded counts with denominators, not proof of cause. The registry summary does not supply attribution details for the deaths or serious events. Overall, the results support a statistical comparison for the defined trial endpoint; they should not be expanded into claims about outcomes, mechanisms, or populations not assessed by these posted data.

18. Why This Trial Matters Statistically

This trial is statistically informative because it uses random allocation and a placebo comparator to evaluate a clearly defined event in a specified population and follow-up period. The primary outcome is not simply RSV detection: it requires clinical symptoms and signs together with a positive RSV test. That definition makes the estimand more specific, while also limiting conclusions to illnesses meeting those criteria.

The results illustrate why effect measures should be read on their own scales. The registry-reported efficacy estimate and the recalculated absolute risk difference both summarize the primary comparison, but their numerical values are not directly comparable. The counts and denominators make the absolute difference interpretable, while the registry-reported exact-method analysis gives the sponsor’s recorded efficacy summary. Confidence intervals add information about precision that a p-value alone does not provide.

The study also shows why analysis populations and follow-up windows matter. The primary analysis excludes randomized participants who did not receive a dose or were not protocol compliant, according to the stated population definition. The registry reports separate safety denominators, and the secondary MALRI outcome has a longer follow-up window than the primary endpoint. These distinctions affect which participants and events each result represents.

Finally, interpretation depends on reporting completeness. The record contains primary and secondary results and safety summaries, but does not report the original sample-size justification, multiplicity procedures, missing-data handling, or full statistical plan. Recognizing both the strengths of a randomized comparison and the limits of available analysis detail is central to a careful statistical reading.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary analysis population is described as randomized participants who received treatment and were protocol compliant, rather than all enrolled participants. The registry does not provide the number or characteristics of participants omitted from this population, the reasons for any exclusions, or the operational definition of protocol compliance. This limits assessment of how the analysis population relates to all randomized participants.

The registry record does not report the amount or pattern of missing endpoint data, the method used to handle missing outcomes, or sensitivity analyses for missingness. It also does not provide the original sample-size justification, full statistical analysis plan, or interim-analysis details. The planning illustrations are not a substitute for the trial’s own design rationale.

The primary outcome combines outpatient and inpatient cases. Separate primary counts by care setting are not reported. The endpoint requires a clinical definition and RSV-positive testing, so conclusions apply to cases meeting those criteria, not to all RSV infections or respiratory symptoms. The primary period is Day 1 to Day 150; the secondary MALRI outcome extends to Day 180, complicating direct comparison across those results.

The registry lists multiple outcomes but does not report multiplicity control. The secondary p-values are unadjusted, so they carry less confirmatory weight. Safety summaries are descriptive; the posted counts do not include causal attribution for serious events or deaths. The Season 2 results concern an eligible subset from Season 1 and should not be interpreted as an independent cohort comparison. These limitations do not erase the posted findings, but they define what can be concluded from the registry information.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Clesrovimab (MK-1654) in Infants (MK-1654-004) — NCT04767373.
• Registry record last updated 2026-02-11; status last verified 2026-01.
• Results first posted 2025-02-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT04767373 is a completed randomized, double-blind, parallel-group, placebo-controlled Phase 2b/3 study of clesrovimab in healthy pre-term and full-term infants. The registry lists 3632 participants enrolled. The primary endpoint was the number of participants with RSV-associated MALRI in RSV Season 1 from Day 1 postdose to Day 150.

The primary analysis included 60 of 2398 participants in the clesrovimab group and 74 of 1201 in the placebo group. The registry-reported efficacy estimate was 60.4, with a 95% confidence interval from 44.1 to 71.9 and p < 0.001. The unadjusted recalculated risk difference was -0.037, with a 95% confidence interval from -0.052 to -0.022.

The record also posts Season 1 hospitalization and MALRI secondary results and adverse-event summaries for Season 1 and Season 2. Multiplicity procedures, missing-data handling, the original sample-size justification, and full statistical-plan details are not reported in the registry record.