Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants (NCT03881696), a randomized phase 3 study. The primary outcome is Number of Participants by Stage 1 Treatment Assignment, Omalizumab Versus Placebo, Who Successfully Consume a Single Dose of ≥600 mg of Peanut Protein Without Dose-Limiting Symptoms During the DBPCFC Conducted at the End of Treatment Stage 1.

2. Clinical Question

3. Trial Design

CoFAR-11 is a Phase 3, randomized, triple-masked, sequential-model study. The registry describes it as multi-center, double-blind, and placebo-controlled. Enrollment is listed as 458, and the study status is completed. The overall study population included children and adults aged 1 to less than 56 years with peanut allergy and allergy to at least two other specified foods.

Stage 1 randomized participants to omalizumab or placebo for omalizumab. Treatment was given by subcutaneous injection every 2 weeks or every 4 weeks for 16 to 20 weeks, with the dose and interval determined from serum total IgE and body weight. The primary food challenge was conducted at the end of Stage 1 treatment. The primary outcome population is narrower than the full age range described for study eligibility: it is identified as the pediatric Stage 1 Full Analysis Set.

The record also describes an open-label extension after Stage 1, with 24 weeks of omalizumab for participants following the described extension pathway. Stage 2 included pathways involving omalizumab-facilitated multi-allergen oral immunotherapy or omalizumab with placebo oral immunotherapy. In the facilitated pathway, omalizumab and multi-allergen oral immunotherapy were given together for eight weeks, followed by placebo for omalizumab alongside oral immunotherapy for 44 weeks. In another pathway, open-label omalizumab was given with placebo oral immunotherapy for eight weeks, followed by omalizumab with placebo oral immunotherapy for 44 weeks.

Stage 3 is described as a treatment plan following food challenges, with separate plans for peanut and each of two other participant-specific foods. The registry describes these as sequential stages and pathways; it does not report enough detail to reconstruct every participant’s progression through them. The study started on 2019-07-22, and primary completion is listed as 2023-03-13.

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: 458 unique participants were enrolled during the recruitment period. 13 participants were re-screened. 276 of the participants that enrolled did not meet the required eligibility criteria and therefore were considered trial screen failures. 180 participants went on to randomize in Stage 1. 2 participants met eligibility criteria after Stage 1 was completed and were randomized directly into Stage 2.

Only the first 6 of 9 groups are shown.

Stage 1

Reasons for not completing this period:

Stage 1 OLE

Stage 2

Reasons for not completing this period:

Start of stage 3 through 6 months

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pediatric Full Analysis Set - Stage 1 (PFA-S1): All participants aged less than 18 years at randomization who have been randomized to either omalizumab or placebo for omalizumab in Stage 1. Participants will be analyzed according to the treatment arm to which they were randomized in Stage 1, regardless of the treatment actually received in Stage 1.

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: Full Analysis Set - Stage 1 (FA-S1): All participants who have been randomized to receive either omalizumab or placebo for omalizumab in Stage 1. Participants will be analyzed according to the treatment arm to which they were randomized in Stage 1, regardless of the treatment actually received in Stage 1.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants by Stage 1 Treatment Assignment, Omalizumab Versus Placebo, Who Successfully Consume a Single Dose of ≥600 mg of Peanut Protein Without Dose-Limiting Symptoms During the DBPCFC Conducted at the End of Treatment Stage 1, measured over During the DBPCFC at the end of Stage 1: 16 to 20 weeks after Stage 1 treatment initiation.

The primary endpoint counts participants who successfully consume a single dose of at least 600 mg of peanut protein without dose-limiting symptoms during a double-blind placebo-controlled oral food challenge. The challenge took place in a controlled clinic setting at the end of Stage 1, 16 to 20 weeks after Stage 1 treatment initiation. The registry defines dose-limiting symptoms as symptoms that, in the principal investigator’s view, indicate a true allergic reaction.

This is a binary outcome at the participant level: each participant either meets the specified challenge criterion or does not. The count is intended to compare the Stage 1 omalizumab and placebo groups on a concrete, prespecified food-challenge threshold, rather than to describe a continuous change in a laboratory measurement or symptom score. The registry’s broader objective concerns the ability to consume foods without dose-limiting symptoms during a challenge.

The endpoint has a defined scope. It concerns one specified peanut-protein dose, one challenge time, and the stated pediatric Stage 1 analysis population. While participants could have allergies to more than two other foods, the primary endpoint and related assessment were limited to peanut and two other participant-specific foods. The registry record does not report the primary endpoint result or a treatment-effect estimate, so the endpoint definition alone cannot establish how the randomized groups compared.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint, the underlying observation is whether each participant meets a stated criterion. In this trial, the criterion is successful consumption of the specified peanut-protein dose without dose-limiting symptoms during the challenge. A group count is the number of participants meeting that criterion. To interpret a count as a rate, the number assessed in that group is also needed. A comparison then summarizes how the outcome frequency differs between randomized groups, with an uncertainty measure describing how much the estimate could vary because of sampling.

What would an effect estimate describe?

General statistical explanation: a difference in proportions describes the absolute separation between group outcome frequencies. A ratio compares those frequencies relative to one another. Each answers a different question, and neither replaces the underlying counts and denominators. Confidence intervals express uncertainty around an estimate; they do not identify a range in which every individual participant’s outcome will fall. A narrow interval indicates greater precision for the estimated group contrast than a wide interval, while the interval’s position relative to a null value is relevant to statistical interpretation.

No primary group counts, effect estimate, or confidence interval are reported in the registry record. Consequently, the size and precision of the primary contrast cannot be described. No recalculated estimate is available to compare with a sponsor analysis, and no significance test result should be inferred from the endpoint definition or study design alone.

Why does the randomized comparison matter?

General statistical explanation: random assignment is intended to make the groups comparable on average at the start of a trial, including for characteristics that were not measured. A comparison based on the randomized assignment can preserve that design feature when participants are analyzed according to their assigned group. The registry identifies the pediatric Stage 1 Full Analysis Set and says participants were randomized to omalizumab or placebo for omalizumab. The available description does not fully state the analysis rules for every participant or how missing challenge assessments were handled, so those details cannot be assumed.

Masking can help limit differences in participant, clinician, or assessor expectations from affecting treatment delivery or outcome assessment. The registry lists triple masking and describes Stage 1 as double-blind and placebo-controlled. The record does not specify the roles covered by each masking label, so the exact implementation should not be inferred from those labels.

What does the sample-size illustration mean?

General statistical explanation: a sample-size calculation estimates how many participants would be needed under stated assumptions to detect a chosen effect with a specified statistical procedure. The record describes an illustration using a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of the observed effect. Such planning illustrations are not observed power and do not show that a trial had a particular probability of detecting its result after the data were collected. The record does not give the trial’s own sample-size justification or enough information to interpret particular illustration values.

Planning estimates depend on assumptions about the outcome frequency, target effect, allocation, and statistical method. If the assumed effect is smaller, detecting it generally requires more information; this is a general relationship, not a calculation for this trial. Any planning illustration based on an observed effect is especially distinct from a prospective design justification because the illustration uses an effect estimate as an input. It cannot establish the original investigators’ rationale. The trial’s protocol-based sample-size justification is not reported in the registry record.

How should multiple outcomes be considered?

General statistical explanation: when many outcomes or analyses are examined, the chance of at least one apparently unusual result can increase if each is assessed independently without an adjustment or hierarchy. Multiplicity procedures can control particular error rates, but they need to be specified and interpreted in the context of the analysis plan. The registry lists 97 outcome measures and 104 analyses. It does not report the multiplicity strategy, a primary-to-secondary testing hierarchy, or whether particular analyses were exploratory. Counts of measures and analyses alone do not show whether a statistical correction was used.

Several secondary outcomes concern successful consumption of specified doses of milk, egg, wheat, cashew, or hazelnut protein during food challenges. These are distinct endpoints, not substitutes for the primary peanut endpoint. Their presence increases the importance of knowing which analyses were prespecified and how results were intended to be interpreted together. The relevant analysis plan is not reported in the registry record.

What role does over-dispersion play?

General statistical explanation: over-dispersion is a concern for some count-data models when observed variation exceeds what a model assumes. It is not the defining issue for this primary endpoint, which is described as a participant count meeting a binary criterion. Methods for binary outcomes instead depend on the treatment contrast, group denominators, and assumptions of the chosen model. The registry does not report the statistical model used for the primary comparison, so no model-specific assumptions can be evaluated.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 97 outcome measures and 104 analyses. These counts indicate a broad set of planned or recorded assessments, but they do not specify how the primary endpoint was prioritized relative to secondary outcomes, whether testing was hierarchical, or whether any multiplicity adjustment was used. The multiplicity strategy is not reported in the registry record. Without it, a reader cannot determine how the investigators intended to control the risk of false-positive findings across analyses or distinguish confirmatory from exploratory comparisons.

The primary outcome has not been reduced to one reported comparison in the registry record. The record does identify the pediatric Stage 1 Full Analysis Set, including participants aged less than 18 years at randomization who were randomized to Stage 1 omalizumab or placebo. It does not fully report the analysis population rules, the handling of participants who did not complete a challenge, or the handling of missing outcome data. Missing-data methods and the number of missing primary assessments are not reported in the registry record.

These omissions matter because a binary challenge outcome depends on both the outcome classification and the set of participants included in the analysis. Excluding participants without an observed challenge result, treating them as not meeting the criterion, or using another approach can lead to different estimates. These are general possibilities, not claims about what the investigators did. The analysis plan, any interim analyses, and the protocol-based sample-size justification are not reported in the registry record. The available record therefore does not support a detailed assessment of multiplicity control, missing-data sensitivity, or the complete analysis-population strategy.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypersensitivity (30.5%), enterovirus infection (3.3%), rhinovirus infection (3.3%), status asthmaticus (3.3%), subchorionic haemorrhage (2.0%).

The registry reports serious adverse-event figures for groups identified by treatment stage or pathway. In Stage 1, the omalizumab group lists 4 participants affected among 120 at risk, and the placebo-for-omalizumab group lists 1 among 60. The open-label extension groups list 0 among 39 and 0 among 21, respectively. Stage 2 lists 18 among 59 for omalizumab-facilitated oral immunotherapy and 0 among 58 for omalizumab with placebo oral immunotherapy. Stage 3 lists 8 among 60 from the extension pathway, 3 among 30 from the Stage 2 facilitated pathway, and 5 among 51 from the Stage 2 placebo oral immunotherapy pathway. The registry lists 0 deaths in each group.

The record also lists other adverse events separately from serious adverse events. These are counts of participants affected, not a measure of severity equivalent to the serious-event count. The reported most frequent serious-event terms include Hypersensitivity at 30.5%, Enterovirus infection at 3.3%, Rhinovirus infection at 3.3%, Status asthmaticus at 3.3%, Subchorionic haemorrhage at 2.0%, and Nausea at 1.7%. The denominator for these term percentages is not reported in the registry record.

These figures are descriptive and span different stages and pathways. They should be read with their listed group sizes and treatment histories, not combined into a single randomized safety comparison. The registry record does not provide the context needed to attribute an event to treatment.

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

The registry record establishes a specific primary question: whether participants in the pediatric Stage 1 analysis population met a defined peanut food-challenge threshold after randomization to omalizumab or placebo for omalizumab. It also establishes the timing and setting of that assessment. Those design details clarify what the trial intended to measure, but they are not a substitute for the observed outcome data.

The primary outcome comparison is not reported in the registry record. As a result, the record does not support a conclusion about which Stage 1 group had more participants meeting the challenge criterion, the magnitude of any group difference, or the precision of that difference. It also does not support a statement that the treatment did or did not work. Such conclusions would require the primary outcome results and their statistical analysis.

Even if a primary challenge result were available, its meaning would be bounded by the endpoint. It would describe performance at the specified dose during a controlled clinic challenge at the end of Stage 1. It would not automatically describe response to every food allergen, outcomes beyond the assessed foods, or outcomes at other times. The study enrolled participants with peanut allergy and at least two other food allergies, but the primary endpoint was assessed for peanut and two participant-specific additional foods.

The safety counts answer a different descriptive question: how many participants in the listed stage or pathway groups were recorded as affected by serious or other adverse events. They do not supply the missing primary efficacy comparison, and the different stage groups should not be interpreted as though all arose from one simple parallel-group comparison. The sequential structure and the later groups’ treatment histories need to remain part of the interpretation.

Overall, the record documents the trial design, endpoint definition, and several safety counts, but leaves the main randomized outcome comparison unavailable. Statistical conclusions about the primary endpoint, its uncertainty, and the importance of any secondary findings are therefore not established by the reported information.

13. Why This Trial Matters Statistically

CoFAR-11 illustrates why a clearly defined endpoint and a reported result are both necessary for statistical interpretation. The primary endpoint is concrete: a participant either does or does not consume the specified peanut-protein dose without dose-limiting symptoms during a controlled challenge. Its definition makes the intended measurement understandable, while its timing identifies the assessment point after Stage 1 treatment.

The study also illustrates the difference between the overall eligible population and the population used for a particular analysis. Eligibility covered children and adults aged 1 to less than 56 years, whereas the stated primary analysis population is pediatric and limited to participants randomized in Stage 1. That distinction matters when judging the scope to which a result would apply. A result for a specified analysis population should not be described as though it necessarily represents every participant covered by the broader eligibility criteria.

The sequential design makes context important. The record describes Stage 1 randomization, an open-label extension, later Stage 2 pathways, and Stage 3 treatment plans following challenges. Stage-specific adverse-event counts belong to those different contexts. Readers need the treatment history and group definition alongside the count, rather than assuming every listed group is a direct randomized comparison.

Finally, the registry lists many outcome measures and analyses but does not report the multiplicity strategy or the primary outcome comparison. This combination highlights why a result requires more than a p-value or a list of outcomes: the estimate, uncertainty, analysis population, missing-data approach, and testing plan all contribute to its interpretation. Here, the endpoint and design are described, but the missing primary comparison prevents assessment of the central statistical question.

14. 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.

A principal limitation of the registry record is that it does not report the primary endpoint comparison. Without the group outcome counts and denominators, a treatment-effect estimate and its uncertainty cannot be assessed. The record’s primary endpoint description is also specific to the pediatric Stage 1 Full Analysis Set, while eligibility covers a broader age range; conclusions about the wider eligible population would require relevant results for that population.

The endpoint is bounded by a food challenge at the end of Stage 1 and by a single specified peanut-protein dose. The study includes participants who could be allergic to several foods, but the primary assessment is limited to peanut and two other participant-specific foods. The outcome therefore does not represent every possible food allergy or every possible challenge dose. The registry does not report the primary outcome comparison for those assessments either.

The sequential structure complicates any simple reading across all reported groups. Some safety groups are defined by prior Stage 1 treatment, open-label extension, or Stage 2 pathway. They should not be treated as one common randomized contrast. The registry does not provide enough information to reconstruct every participant’s pathway or to determine how transitions between stages relate to the reported safety figures.

Other specific limitations are the absence of reported details on missing primary assessments, analysis rules beyond the stated population, multiplicity handling, interim analyses, and the protocol-based sample-size justification. The denominator for the listed serious-event term percentages is not reported in the registry record. These gaps limit assessment of precision, robustness, and the intended interpretation of multiple analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants — NCT03881696.
• Registry record last updated 2026-09-22; status last verified 2026-09.
• Results first posted 2024-06-04.
• 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.

18. Record Summary

CoFAR-11, titled “Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants,” is a Phase 3 randomized, triple-masked, sequential-model study. The registry describes a multi-center, double-blind, placebo-controlled trial of participants aged 1 to less than 56 years with peanut allergy and allergy to at least two other foods. Enrollment is listed as 458, and the study status is completed.

The primary endpoint concerns successful consumption of a single dose of at least 600 mg of peanut protein without dose-limiting symptoms during a food challenge at the end of Stage 1. The stated primary analysis population is pediatric. The primary outcome comparison is not reported in the registry record. Safety counts are listed for groups across Stage 1 and later pathways, with 0 deaths recorded in every listed group.

The study started on 2019-07-22, with primary completion on 2023-03-13. The sponsor is the National Institute of Allergy and Infectious Diseases (NIAID).