A Trial to Test if Fremanezumab is Effective in Preventing Migraine in Children and Adolescents: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Test if Fremanezumab is Effective in Preventing Migraine in Children and Adolescents (NCT04530110), a na phase 3 study. The primary outcome is Number of Participants With Adverse Events (AEs).

2. Clinical Question

In practical terms, the registry describes a study of safety and tolerability during ongoing preventive treatment, with additional planned assessment of migraine outcomes and antidrug antibodies. The outcome list includes changes in monthly average headache days of at least moderate severity, migraine days, use of acute headache medication, and migraine-related disability measured by the PedMIDAS questionnaire. It also includes the proportions reaching at least 50% reductions in migraine days or headache days of at least moderate severity.

The record does not establish a comparison with placebo, usual care, or another preventive treatment. It therefore supports a descriptive reading of outcomes among participants who received fremanezumab, not a randomized estimate of the difference treatment would make relative to a control. The posted adverse-event figures can be read as safety counts within the dose groups, while the registry record does not report efficacy estimates or a full analysis of the primary endpoint.

3. Trial Design

This is a Phase 3, open-label study with a single-group model and no randomized allocation. The intervention is fremanezumab administered monthly by subcutaneous injection. According to the arm description, dose confirmation or adjustment was to be based on participant weight every 3 months. The registry lists two dose groups, Fremanezumab 120 mg and Fremanezumab 225 mg, but their presence does not make the study a randomized comparison: allocation is recorded as not applicable, and the record identifies the arms as unsuitable for a like-for-like control comparison.

The registry lists an enrollment of 499. The safety analysis set included all participants who received at least 1 dose of investigational medicinal product. The posted safety groups give their own numbers at risk; those group figures should be interpreted as reported rather than treated as evidence of a randomized allocation. The record does not explain how participants entered each dose group beyond the weight-based dose description.

The study status is completed. The listed start date is 2020-09-16, and the listed primary completion date is 2025-08-15. The brief summary describes the total study duration as planned to be up to 84 months. That planned duration is not the same as the primary endpoint timeframe, which is Day 1 up to Day 393.

The primary objective was to evaluate long-term safety and tolerability. Secondary objectives were to evaluate efficacy and immunogenicity, including the impact of antidrug antibodies on clinical outcomes. The sponsor is Teva Branded Pharmaceutical Products R&D LLC. The registry record does not report the detailed protocol, the rationale for the sample size, the planned statistical methods, or whether interim analyses were conducted. It also does not report a concurrent comparator or masking; masking is listed as none.

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: A total of 499 participants were enrolled and evaluated in the trial.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety analysis set included all participants who received at least 1 dose of IMP.

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: The intent-to-treat (ITT) analysis set included all enrolled participants, regardless of whether a participant took investigational medicinal product (IMP).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), measured over Day 1 up to Day 393.

The primary endpoint is the number of participants with adverse events, reported as a participant count, over the timeframe from Day 1 up to Day 393. The registry defines an adverse event as any untoward medical occurrence in a participant who received study drug, without regard to whether a causal relationship to the drug was considered possible. This definition is broad: it records medical occurrences, not only events judged to be caused by treatment.

A participant count is a way to describe how many people experienced an event during the specified period. It is different from a count of all event episodes, because a participant may experience more than one event. The endpoint, as named, is about participants with adverse events, and the stated safety analysis set includes participants who received at least 1 dose of study drug.

Safety endpoints of this kind are used to summarize the types and frequency of medical occurrences observed during exposure. In general, including events without requiring a causal link can help avoid excluding an occurrence merely because its relationship to treatment is uncertain. It does not, by itself, show that treatment caused an event.

The registry also directs readers to the reported adverse-event section for other non-serious adverse events and all serious adverse events, regardless of causality. The posted group figures distinguish serious events and other events, but the registry record does not give a single overall primary-endpoint count of participants with any adverse event in the material. Nor does it report a comparative estimate against a control group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies this as a Phase 3, open-label, single-group study. These design features determine what statistical conclusions the posted information can support. An open-label study does not mask treatment assignment from participants or study staff, and this record lists masking as none. A single-group model does not provide a randomized control arm. Although the record presents two fremanezumab dose groups, it says allocation is not applicable and identifies the arms as not a like-for-like control comparison. Any difference between their reported counts would therefore be descriptive rather than a randomized estimate of a dose effect.

What does a participant count tell us?

The primary endpoint is a count of participants with adverse events during Day 1 up to Day 393. The safety analysis set includes all participants who received at least 1 dose of study drug. The registry’s safety table gives numbers at risk and counts affected for serious adverse events and other adverse events within each dose group. A count of participants affected answers how many people are represented in that category; it is not necessarily a count of every event episode. One participant could have more than one medical occurrence, and the endpoint definition focuses on participants rather than event totals.

The broad adverse-event definition includes any untoward medical occurrence after receipt of study drug, without requiring a judgment that the drug could have caused it. This approach is useful for descriptive safety monitoring because events can be recorded before their causal relationship is clear. Causality and occurrence are separate questions: an event may occur during a study without being caused by the intervention. The posted counts should therefore be read as events observed in participants exposed to treatment, not as counts of events established to be treatment-related.

Why does the absence of a control group matter?

In general, a concurrent control group helps distinguish outcomes observed under treatment from outcomes that might also occur without that treatment. Random allocation can make groups more comparable on average, supporting a causal comparison when the analysis is appropriate. Here, there is no randomized control group. The registry’s two dose groups do not replace one: the record describes weight-based dose confirmation or adjustment and does not describe random allocation between doses. The study can report what was observed among participants receiving fremanezumab, but it cannot use the posted design to estimate a randomized treatment-versus-control contrast.

Open-label status is also relevant when outcomes require judgment or participant reporting. Knowledge of treatment can influence reporting, assessment, or study conduct. This is a general methodological concern, not evidence that bias occurred in this particular study. The registry record does not report masking procedures beyond listing none, or details that would allow the size or direction of any such influence to be assessed.

How should uncertainty be assessed?

In general, a point estimate summarizes the observed data, while a confidence interval describes statistical uncertainty under a stated model and assumptions. A p-value addresses compatibility with a specified null hypothesis under those assumptions; it is not a measure of clinical importance. For simple counts, the uncertainty depends on the number of participants and the analysis method. For comparisons, it also depends on the design and the contrast being estimated. The registry record lists no analysis results, estimates, confidence intervals, or p-values for the outcomes. It is therefore not possible to assess the precision of the posted safety counts through reported inferential statistics.

The count of 0 deaths in each group is the count posted for this study. It does not, by itself, establish that the risk of death is zero, nor does it provide a comparison with another population. In general, a zero observed count can still be compatible with a range of underlying risks; the width of that range depends on the amount of information and the method used. No uncertainty interval for deaths is reported in the registry record.

What do the planning illustrations represent?

Any sample-size illustrations on the page are planning illustrations, not the trial’s own design calculation and not observed power. The described assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm; time-to-event illustrations, where relevant, use a total event count. These assumptions describe a hypothetical planning exercise. They do not establish that the trial was randomized, equally allocated, or designed around the illustrated effect.

Observed power is not a substitute for estimates and uncertainty intervals after a study is complete. In general, planning calculations answer a prospective question about the sample size associated with chosen assumptions. They do not summarize the precision of the trial’s actual findings. The registry record does not report the trial’s sample-size justification or enough outcome analyses to assess how well the observed data estimate effects.

What is not available for independent interpretation?

The record lists 14 outcome measures and no analysis results. It names secondary measures but does not give their estimates or statistical tests. The detailed analysis plan, methods for handling missing observations, any covariate adjustments, and any interim analyses are not reported in the registry record. Those omissions limit assessment of how the planned outcomes were analyzed and whether the posted counts represent all relevant observations. They also prevent reconstruction of a more detailed statistical interpretation from the registry alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Fremanezumab 120 mg", "Fremanezumab 225 mg")
n      <- c(100, 398)
events <- c(78, 294)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Fremanezumab 120 mg  100  78  78.0  68.6  85.7  68.9  85.0  68.9  85.0
ARM  Fremanezumab 225 mg  398  294  73.9  69.3  78.1  69.3  77.9  69.3  77.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, including the primary safety endpoint and multiple secondary measures of migraine symptoms, medication use, disability, and immunogenicity. When a study evaluates several outcomes, multiplicity can arise because repeated statistical testing increases the chance of at least one apparently notable result by chance. In general, a prespecified hierarchy or adjustment can address this issue, but the approach depends on the study’s objectives and analysis plan. The statistical plan and any multiplicity adjustment are not reported in the registry record. No outcome analysis results are listed, so the effect of multiplicity on reported conclusions cannot be assessed.

Missing data also matter for changes from baseline and response outcomes. In general, the interpretation can depend on why observations are missing and how the analysis handles them. Methods might use different assumptions about unavailable measurements, and those assumptions can affect estimates. The registry record does not report missing-data methods, the extent of missingness, or sensitivity analyses. It is therefore not possible to determine from this record how incomplete follow-up was handled for the secondary outcomes.

The primary safety population is described as all participants who received at least 1 dose of investigational medicinal product. That definition identifies who was eligible for the safety analysis set, but the registry record does not provide a full account of participant flow, exposure duration, or the analysis populations used for each secondary outcome. The analysis population for efficacy measures and the handling of participants with no follow-up measurements are not reported in the registry record.

These are limits on interpretation, not evidence that a particular method was or was not used. The registry record does not report the statistical analysis plan, the treatment of multiplicity, or the procedures for missing data and outcome-specific populations. Without those details and the analysis results, the outcome list should not be treated as evidence that each planned measure produced a reported finding.

12. 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: appendicitis (1.0%), covid-19 (1.0%), influenza (1.0%), migraine (1.0%), gastritis (0.5%).

The registry lists serious adverse events and other adverse events separately for the two fremanezumab groups. For Fremanezumab 120 mg, the serious-event count is 4 among 100 at risk and the other-event count is 56 among 100 at risk. For Fremanezumab 225 mg, the corresponding counts are 17 among 398 at risk and 229 among 398 at risk. The death count is 0 for each group. These are the posted figures; they are not a randomized comparison between doses.

The registry defines an adverse event broadly as an untoward medical occurrence after a participant received study drug, regardless of whether a causal relationship was considered possible. Thus, these counts describe events recorded during the study and do not establish that fremanezumab caused them. The record directs readers to the reported adverse-event section for other non-serious events and all serious events, regardless of causality.

The listed serious-event terms include Appendicitis, COVID-19, Influenza, and Migraine at 1.0% each, and Gastritis and Pyelonephritis at 0.5% each. The excerpt does not show the counts or denominators for these term-level percentages. The registry record also does not provide a comparative risk estimate or uncertainty interval for these safety figures. Read the counts as descriptive observations within the study groups, not as proof of causation or as a comparison with an untreated group.

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

The record describes a long-term, open-label study of fremanezumab in pediatric participants with migraine, with safety and tolerability as the primary objective. It gives counts for serious and other adverse events in two dose groups and lists several serious-event terms. Those data show what was recorded in the study groups over the reported safety period. They do not, on their own, determine whether an event was caused by treatment or how the event rate compares with what would have occurred without treatment.

The study’s design is central to that distinction. The registry lists a single-group model, no masking, and allocation as not applicable. The dose groups are not described as randomized controls. As a result, the posted information does not estimate a treatment effect relative to placebo, usual care, or another preventive treatment. Nor does it establish that differences between the dose groups are caused by dose; participants’ dose could be confirmed or adjusted based on weight every 3 months.

The registry also names secondary efficacy outcomes, including migraine days, headache days, acute medication use, disability, and response proportions. It does not provide analysis results for those outcomes in the record. The outcome list indicates what was to be assessed, not what was observed or how precisely it was estimated. No efficacy estimate, confidence interval, or p-value is reported in the registry record.

In general, an observed count is most informative when read alongside the population observed, the time period, the outcome definition, and uncertainty. Here, the safety analysis set is described, the primary endpoint timeframe is stated, and adverse events are defined. However, a complete overall count for the primary endpoint and inferential analyses are not reported in the registry record. This limits conclusions about precision and comparative risk.

The study therefore contributes descriptive safety information for participants who received fremanezumab, along with a record of the outcomes planned for evaluation. It does not provide a randomized comparison or the posted efficacy analyses needed to quantify comparative benefit. These boundaries are about what the registry record can support; they are not a recommendation about treatment or an assessment of an individual participant’s care.

14. Why This Trial Matters Statistically

This study is statistically informative in part because its design and endpoint make the limits of safety interpretation visible. The primary endpoint counts participants with adverse events, using a broad definition that does not require a causal link. That is a clear descriptive safety question: what medical occurrences were recorded among participants who received study drug during the stated period? It is different from asking how many events were caused by treatment or whether treatment changed risk compared with an alternative.

The distinction between a single-group study and a controlled comparison is especially important when a record lists multiple dose groups. Two groups can look like a comparison in a table, but a causal interpretation depends on how participants were assigned and whether the groups are comparable. Here, the registry lists allocation as not applicable, describes a single-group model, and notes that the arms are not a like-for-like control comparison. Those features mean the counts should remain descriptive.

The outcome list also illustrates why planned outcomes and analyzed results must be distinguished. Migraine days, headache days, medication use, disability, and antidrug antibodies are named as secondary measures. But without reported estimates, uncertainty intervals, or analysis methods, readers cannot judge the magnitude or precision of any efficacy finding from this record. Multiple outcomes also raise general questions about prespecification and multiplicity, whose handling is not reported in the registry record.

Finally, the safety population and event definitions provide useful context for interpreting the posted counts, while missing-data procedures and the detailed analysis plan remain unavailable. These features help readers identify what can be said and what remains uncertain. Statistical importance lies not in treating descriptive counts as a comparative result, but in matching the strength of the interpretation to the study design and the analyses actually reported.

15. 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 most important limitation for comparative interpretation is the absence of a randomized control group. The study is listed as open-label and single-group, with allocation recorded as not applicable. The two listed dose groups do not provide a like-for-like control comparison. Consequently, the registry’s adverse-event counts cannot establish the difference in risk between fremanezumab and no treatment or another intervention. They also cannot establish a causal dose contrast.

The primary endpoint is defined as the number of participants with adverse events, but the posted figures separate serious adverse events and other adverse events. A single overall primary-endpoint result is not reported in the registry record. The safety table gives counts at risk and affected for the listed categories, but no confidence intervals or comparative estimates. The registry record lists no analysis results, limiting assessment of precision beyond the descriptive counts.

The study is open-label, and masking is listed as none. In general, knowledge of treatment may influence reporting or assessment, particularly for outcomes involving participant reports or clinical judgment. This is a possible design consideration, not evidence that an influence occurred. The registry record does not provide further details that would allow its impact to be evaluated.

The record does not report the detailed statistical analysis plan, sample-size justification, multiplicity approach, missing-data methods, or interim analyses. It also does not report the analysis results for the named secondary efficacy and immunogenicity outcomes. The dose description notes weight-based confirmation or adjustment every 3 months, but further details about group assignment and exposure are not reported in the registry record.

These limitations do not invalidate the posted observations, but they narrow what can be concluded from them. They support a descriptive account of the safety data shown, not a controlled estimate of treatment effect or a complete assessment of efficacy.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Trial to Test if Fremanezumab is Effective in Preventing Migraine in Children and Adolescents — NCT04530110.
• Registry record last updated 2026-07-24; status last verified 2026-06.
• Results first posted 2026-07-24.
• 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.

19. Record Summary

The registry describes a completed Phase 3, open-label, single-group study of monthly subcutaneous fremanezumab in pediatric participants with migraine. The official title covers episodic and chronic migraine in participants aged 6 to 17 years. Enrollment is listed as 499; the dose was to be confirmed or adjusted based on weight every 3 months. The primary objective was long-term safety and tolerability, with efficacy and immunogenicity as secondary objectives.

The primary endpoint was the number of participants with adverse events from Day 1 up to Day 393. The posted safety figures distinguish serious and other adverse events across the Fremanezumab 120 mg and Fremanezumab 225 mg groups. The study has no randomized control group, and the registry lists no analysis results. Detailed statistical methods, missing-data handling, and results for secondary outcomes are not reported in the registry record.