Efficacy, Safety, and Pharmacokinetic Profiles of REGN3500 Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy, Safety, and Pharmacokinetic Profiles of REGN3500 Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis (NCT03738423), a randomized phase 2 study. The primary outcome is Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16.

2. Clinical Question

The clinical question is whether REGN3500 monotherapy, across the studied dose schedules, was associated with a different Week 16 change in atopic dermatitis severity than placebo, and how the observed response varied by dose. The registry describes efficacy and dose-response as the primary objectives, with safety, tolerability, pharmacokinetics, and immunogenicity as secondary objectives.

The primary outcome is a continuous measure: percent change from baseline in the Eczema Area and Severity Index (EASI) score. It is not a direct measure of every feature of atopic dermatitis or of how participants experienced their condition. EASI combines assessments of erythema, induration, excoriation, and lichenification across four body regions. Because lower EASI scores indicate less severe disease, a negative percent change represents a decrease in the score from baseline.

The registry reports a randomized, parallel-group, placebo-controlled study and describes the study as Phase 2b. The posted primary results are descriptive because of premature discontinuation. Thus, the question addressed by the observed estimates is narrower than a definitive treatment comparison: they describe changes among participants evaluable for this outcome, under the stated handling of rescue treatment.

3. Trial Design

This was a randomized, parallel-group, placebo-controlled dose-ranging study of REGN3500 in adults with moderate-to-severe atopic dermatitis. The official title describes the study as double-blind, while the registry classifies masking as quadruple. The registry lists REGN3500 and a REGN3500-matching placebo as the interventions. The primary objective was to assess REGN3500 monotherapy efficacy and the dose-response relationship relative to placebo. Safety, tolerability, pharmacokinetics, and immunogenicity were secondary objectives.

The registry reports 129 participants enrolled. The overall enrollment figure should not be confused with the number evaluable for a particular outcome. For the primary endpoint, the posted groups contain 10 participants receiving placebo, 7 receiving REGN3500 30 mg Q8W, 7 receiving 100 mg Q4W, 7 receiving 300 mg Q4W, and 9 receiving 300 mg Q2W. The registry explains that the number analyzed for an outcome refers to participants evaluable for that outcome, within a full analysis set defined as all randomized participants analyzed according to allocated treatment.

The study status is terminated. Its start date is 2018-11-13 and its primary completion date is 2020-03-13. The reason for termination and whether it affected each treatment group differently are not reported in the registry record. The registry states that premature discontinuation led to descriptive statistical analyses. It does not report a sponsor-led inferential comparison for the primary endpoint.

Several Week 16 secondary outcomes assess EASI response thresholds, and others assess absolute EASI change. The record distinguishes outcomes where measurements after rescue treatment were set to missing from outcomes using observed values regardless of rescue treatment. Results and participant counts can differ across endpoints because the outcome definitions and evaluable populations differ. The protocol’s intended sample size, allocation ratio, and detailed analysis plan 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 were randomized in 1:1:1:1:1 ratio to 1 of the 5 treatment groups: Placebo every 2 weeks (Q2W); REGN3500 30 milligrams (mg) every 8 weeks (Q8W); REGN3500 100 mg every 4 weeks (Q4W); REGN3500 300 mg Q4W and REGN3500 300 mg Q2W.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

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 (FAS) included all randomized participants and was based on the treatment allocated (as randomized).

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16, measured over Week 16.

The primary endpoint is percent change from baseline in EASI score at Week 16. EASI assesses the severity and extent of atopic dermatitis using erythema, induration, excoriation, and lichenification in the head, trunk, upper extremities, and lower extremities. The score ranges from 0 to 72, with higher scores indicating worse severity. Percent change expresses how the score at follow-up compares with the participant’s baseline score. A negative value therefore indicates a reduction from baseline EASI.

EASI is used because it combines several disease signs and body regions into one continuous score. That makes it possible to describe the magnitude and direction of change, rather than only whether a participant crossed a selected response threshold. The registry also reports EASI-50, EASI-75, and EASI-90 outcomes, which classify participants according to whether their improvement reaches specified thresholds. Those binary outcomes answer a different question from the continuous primary endpoint: they count participants meeting a threshold rather than describing the distribution of score changes.

For the primary endpoint, values after the first rescue treatment were set to missing. This definition means that the reported Week 16 summary does not incorporate post-rescue measurements as observed outcomes. The registry does not report further details about how missing values were handled beyond this stated rule. As a result, the estimate describes observed evaluable outcomes under this endpoint definition, not a complete measurement of every randomized participant’s Week 16 status.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports the primary endpoint as a continuous outcome summarized by the mean and standard deviation. It also states that, because of premature discontinuation, all statistical analyses were descriptive. The registry record does not report a sponsor-led inferential method for the primary comparison, confidence intervals for primary group means, or a primary-endpoint p-value.

What the mean describes

For a continuous outcome, the mean is the arithmetic average of participant values in the group. Here, each value is percent change from baseline in EASI at Week 16 under the rule that measurements after first rescue treatment are missing. The mean conveys the average direction and magnitude of observed change for the evaluable participants. It does not say that every participant had a result close to that average. It also does not, by itself, compare randomized groups in a way that quantifies uncertainty.

The standard deviation describes how spread out individual outcomes are around the group mean. A smaller standard deviation indicates less spread in the observed values; a larger one indicates more. It should not be read as a confidence interval, standard error, or measure of treatment effect. The registry does not report a standard error or confidence interval for the primary endpoint estimates.

What a confidence interval would mean

General statistical explanation: a confidence interval expresses uncertainty about an estimated quantity under a specified statistical procedure. For a between-group effect, it can show which effect sizes are compatible with the data and the method used. It is not a range containing a stated proportion of individual participant outcomes. No primary-endpoint confidence interval is reported in the registry record, so the precision of the primary between-group contrasts cannot be assessed from a posted interval.

How to read the secondary binary results

The secondary EASI-50, EASI-75, and EASI-90 outcomes are binary response measures: a participant either meets the specified improvement threshold or does not. The posted percentages describe the share meeting each threshold among participants evaluated for that outcome. The accompanying secondary comparisons include unadjusted risk differences and confidence intervals. A risk difference expresses the difference between the observed response proportions in the two groups. General statistical explanation: an interval that includes zero is compatible with no difference under the interval method, as well as with effects in either direction; a wide interval indicates substantial uncertainty.

For example, the EASI-50 risk difference comparing REGN3500 30 mg Q8W with placebo is 0.35, with a confidence interval from -0.040 to 0.740 and an unadjusted p-value of 0.096. This is a recalculated, unadjusted comparison rather than a sponsor-reported analysis. The registry does not report analyses for the listed secondary comparisons. Because the study’s inferential analysis plan is not reported, these recalculated statistics should be interpreted as exploratory descriptions rather than as a substitute for a prespecified analysis.

Why small groups affect precision

General statistical explanation: estimates based on small groups tend to be less precise because each observation has more influence on the group summary. For binary outcomes, a small change in the number of participants meeting a threshold can shift the observed percentage notably. For continuous outcomes, unusually high or low values can influence the mean. This is relevant to the small endpoint-specific group counts in the primary results and to the small denominators in the secondary outcomes.

General statistical explanation: over-dispersion means that outcome variability exceeds what a statistical model assumes. If a model does not allow for that extra variability, its uncertainty estimates may be too narrow. The registry does not report an over-dispersion assessment or a model for the primary endpoint, so no claim about either can be made for this trial.

Planning illustrations are not trial results

The sample-size illustrations use the observed effect as a planning reference, not as the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of the stated fraction of the observed effect. The listed quantities are participants per arm for 80% power and participants per arm for 90% power. They are hypothetical planning values, not observed power and not evidence that the trial was designed to achieve those targets. The trial’s own sample-size assumptions and justification are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Placebo Q2W", "REGN3500 30 mg Q8W", "REGN3500 100 mg Q4W", "REGN3500 300 mg Q4W", "REGN3500 300 mg Q2W")
n   <- c(10, 7, 7, 7, 9)
m   <- c(-33.5, -57.9, -52.7, -80, -54)
sp  <- c(41.81, 31.65, 46.64, 10.54, 36.8)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Placebo Q2W  10  -33.500  41.810  -63.409  -3.591
CARM  REGN3500 30 mg Q8W  7  -57.900  31.650  -87.171  -28.629
CARM  REGN3500 100 mg Q4W  7  -52.700  46.640  -95.835  -9.565
CARM  REGN3500 300 mg Q4W  7  -80.000  10.540  -89.748  -70.252
CARM  REGN3500 300 mg Q2W  9  -54.000  36.800  -82.287  -25.713

11. Multiplicity, Missing Data and Analysis Populations

The registry gives a primary endpoint and a set of secondary endpoints, but it does not report a detailed statistical analysis plan, a hierarchy among endpoints, or a method for controlling multiplicity. It therefore is not possible to determine from the registry record whether any particular secondary comparison was intended to support a confirmatory claim. The posted secondary comparisons are unadjusted recalculations, not sponsor-reported inferential analyses.

General statistical explanation: multiplicity arises when several outcomes, doses, time points, or contrasts are examined. Without an adjustment or prespecified testing sequence, the probability of at least one apparently unusual result can rise. This does not mean that any one result is necessarily false; it means that isolated p-values and intervals need cautious interpretation when many comparisons are available. The record lists 25 outcome measures and reports 23 secondary outcome measures, but it does not explain the status of every unposted measure or provide a multiplicity procedure.

Missing-data handling differs by endpoint definition. For the primary EASI outcome, values after the first rescue treatment were set to missing. The registry also lists secondary EASI measures using observed values regardless of rescue treatment and measures with post-rescue values set to missing. The displayed secondary threshold comparisons described in the registry include the all-observed-values definition. The record does not report additional imputation procedures, sensitivity analyses for missing outcomes, or reasons for missingness by group.

The registry describes the full analysis set as including all randomized participants analyzed according to allocated treatment. It clarifies that the number analyzed for an outcome means the participants evaluable for that outcome. This definition does not mean that every randomized participant contributed an observed Week 16 value. Full reasons for the differences between enrollment, safety counts, and endpoint-specific counts are not reported in the registry record.

The registry explicitly states that premature discontinuation resulted in descriptive statistical analyses. It does not describe interim analyses, stopping boundaries, or the reason for termination. These details are important to interpretation but should not be inferred from the termination status alone.

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: breast cancer (4.2%), gastroenteritis norovirus (3.8%), road traffic accident (3.8%).

The registry reports serious adverse events by group among participants at risk. There were no serious adverse events reported for Placebo Q2W, REGN3500 30 mg Q8W, or REGN3500 100 mg Q4W. One participant in the REGN3500 300 mg Q4W group and two participants in the REGN3500 300 mg Q2W group were reported as affected by serious adverse events. The group sizes at risk were 25, 26, 26, 24, and 26, respectively. These safety denominators differ from the primary endpoint denominators.

The record reports one death in the REGN3500 300 mg Q2W group and none in the other groups. The registry does not report a causal relationship between the death or serious adverse events and study treatment in the registry record for this summary. The listed serious adverse event terms include breast cancer at 4.2%, gastroenteritis norovirus at 3.8%, and road traffic accident at 3.8%; the available information does not assign these terms to specific groups.

Serious adverse event counts are descriptive safety observations, not proof of cause or comparative risk. The group sizes are limited, and the registry record does not give enough detail to evaluate duration of exposure, event timing, or relatedness. The absence of a reported serious event in a group does not establish that risk is absent.

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

The posted primary results describe mean Week 16 changes in EASI among participants evaluable for the endpoint, using a rule that sets values after first rescue treatment to missing. The means are negative in each group, indicating decreases from baseline in the EASI score on average. The estimates also show variation in the observed mean change across dose schedules. These are descriptive findings from a study that the registry says was analyzed descriptively because of premature discontinuation.

The results do not establish that REGN3500 caused the observed changes or that one dose schedule is superior to another. The primary endpoint summaries do not include a reported between-group estimate, confidence interval, or p-value. Small group sizes and the absence of a reported primary inferential analysis limit the precision with which comparative effects can be understood. The record also does not give a reason for the trial’s termination.

The secondary outcomes provide additional descriptions of EASI threshold responses, but they do not resolve the limitations of the primary result. Their endpoint definitions differ, including whether observed measurements after rescue treatment are retained. The recalculated secondary comparisons are unadjusted, and the registry does not report a multiplicity plan or sponsor-reported analyses for those comparisons. They should not be treated as confirmatory evidence.

Safety findings are also descriptive. Serious adverse events and the reported death are recorded by group, but the registry information does not establish whether any event was caused by treatment. The number of participants at risk for safety outcomes differs from the number evaluable for the primary endpoint, so the two sets of counts should not be conflated.

General statistical explanation: a trial estimate is most informative when its definition, analysis population, missing-data handling, uncertainty, and analysis plan are all clear. Here, the record describes some of these elements, particularly the rescue-treatment rule and the descriptive nature of the analyses, but does not report all the details needed for a definitive comparative interpretation. The numerical results should therefore be read as observations from this trial, not as a stand-alone determination of treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its randomized, placebo-controlled dose-ranging design is paired with a registry statement that the analyses were descriptive after premature discontinuation. Randomization is a design feature intended to support fair comparisons, but its presence does not by itself supply an inferential estimate or make a small, incomplete set of outcome observations precise. The posted primary summaries should be interpreted according to what was analyzed and reported.

The distinction between overall enrollment and outcome-specific evaluable counts is especially important. The registry reports 129 participants enrolled, while the primary endpoint summaries include groups of 7 to 10 participants. Those figures answer different questions. Enrollment describes the overall trial; the endpoint results describe the participants evaluable for that measure under the stated handling of rescue treatment. This distinction prevents the overall enrollment from being mistaken for the denominator behind each primary estimate.

The trial also illustrates why endpoint definitions matter. Mean percent EASI change and EASI threshold responses are related but not equivalent summaries. Rescue treatment is handled differently by the primary and some secondary outcomes, so their results cannot be compared as if they used the same estimand and observation rules. The registry does not provide enough detail to reconstruct every analysis decision.

Finally, sample-size planning illustrations based on observed effects can be useful for considering future study sizes, but they are not evidence of the trial’s original design or observed power. Their assumptions are stated separately from the trial’s own undocumented sample-size justification. Taken together, the record highlights the need to distinguish design, observed data, analysis population, and inferential certainty rather than treating one favorable-looking number as a complete trial conclusion.

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.

Several limitations are specific to interpreting this registry record. First, the trial is terminated, and the reason for termination is not reported. The record states that premature discontinuation led to descriptive statistical analyses, but does not explain the circumstances or how termination affected follow-up and data availability. That context could matter when judging whether the observed participants represent the randomized population.

Second, the primary endpoint groups are small, with 7 to 10 evaluable participants per group. The overall enrollment of 129 does not change the smaller endpoint-specific denominators. The registry does not provide primary confidence intervals, a primary between-group effect estimate, or a primary p-value, making precision and comparative uncertainty difficult to assess.

Third, rescue treatment is handled by setting post-rescue values to missing for the primary outcome. The record does not provide further missing-data methods, reasons for missingness by group, or sensitivity analyses. The secondary outcomes using all observed values regardless of rescue treatment answer a related but different question. This endpoint variation complicates direct comparisons across results.

Fourth, details of the analysis plan are not reported, including the planned sample-size justification, any interim analyses, and multiplicity control. The listed recalculated secondary comparisons are unadjusted and should not be mistaken for the sponsor’s own statistical analyses. The study’s termination reason, detailed protocol-level analysis decisions, and the relationship of serious adverse events to treatment are also not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy, Safety, and Pharmacokinetic Profiles of REGN3500 Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis — NCT03738423.
• Registry record last updated 2022-06-10; status last verified 2022-05.
• Results first posted 2022-06-10.
• 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 record describes a randomized, parallel-group, placebo-controlled Phase 2b dose-ranging study of REGN3500 monotherapy in adults with moderate-to-severe atopic dermatitis. It reports quadruple masking and an official title that describes the study as double-blind. There were 129 participants enrolled. The study is terminated, with a start date of 2018-11-13 and primary completion date of 2020-03-13.

The primary outcome was percent change from baseline in EASI at Week 16, with values after first rescue treatment set to missing. The registry reports group means and standard deviations for the participants evaluable for this outcome. It states that analyses were descriptive because of premature discontinuation. Secondary EASI response outcomes and safety results are also posted, but detailed inferential methods, multiplicity handling, the sample-size justification, and the reason for termination are not reported in the registry record.