Study of ALXN1820 in Healthy Adult Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of ALXN1820 in Healthy Adult Participants (NCT04631562), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, double-blind, placebo-controlled study of ALXN1820 in healthy participants. The registry describes a sequential study of single and multiple ascending doses administered subcutaneously or intravenously. The listed enrollment was 66, and the study status is completed. The start date was 2021-01-13, with primary completion on 2022-09-01.

The active-treatment cohorts were not all evaluating the same regimen. Cohorts 1 to 4 assessed single-dose SC groups, Cohort 5 assessed a single IV dose, and Cohort 6 assessed another single-dose SC group. Cohorts 8 and 9 are both described as 150 mg SC (QW*5). The registry record describes SC as having single- and multiple-dose cohorts, while IV was evaluated in a single-dose cohort only. It does not explain the sequence in which cohorts were opened or the reason for the cohort numbering.

The registry lists placebo SC and placebo IV as interventions and states that placebo participants received the formulation assigned to their cohort. However, the primary-outcome results are displayed as separate active-treatment cohorts plus one All Placebo group. That structure matters: the posted data do not show a matched placebo group beside every active cohort. The results should therefore be read as cohort-level counts, not as a set of dose-specific randomized contrasts.

The study was designed to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. The registry lists concentration and properdin outcomes among the secondary outcomes. The posted results concern adverse events. The protocol details for cohort progression, allocation ratios, and any statistical 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.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Set included all participants who received at least 1 dose of study drug.

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 Safety Set included all participants who received at least 1 dose of study drug.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV, measured over Cohorts 1 to 6: Baseline up to Day 127; Cohorts 8 to 9: Baseline up to Day 155.

The primary endpoint counts participants with treatment-related treatment-emergent adverse events (TEAEs) for the ALXN1820 SC and IV cohorts. A TEAE is an adverse event that begins after study intervention administration starts. The registry’s general adverse-event definition includes an unfavorable and unintended sign, symptom, or disease that occurs in temporal association with a medicinal product or procedure, whether or not the event is considered related. The primary endpoint narrows that broader category to events judged treatment-related.

This kind of count is useful in a Phase 1 safety assessment because it summarizes how many participants experienced an event meeting the stated criteria during follow-up. It is an event-participant count, not a measure of event severity, duration, or recurrence. A participant with more than one event is still counted as a participant for this endpoint; the registry record does not provide a separate event count.

The stated observation windows differ by cohort: baseline up to Day 127 for Cohorts 1 to 6, and baseline up to Day 155 for Cohorts 8 to 9. The primary-outcome population is the Safety Set, defined as all participants who received at least one dose of study drug. The endpoint is relevant to safety and tolerability, but by itself does not summarize pharmacokinetics, pharmacodynamics, or immunogenicity, which are also named study objectives.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted results use participant counts for the primary endpoint. Each cohort is described by the number of participants in the group and the number counted as having a treatment-related TEAE. This is a straightforward descriptive presentation: it records how many participants met the endpoint definition within each displayed group. The tables and plots present these results; this explanation does not recalculate or replace them.

What does a participant count show?

A participant count answers whether participants met the endpoint definition during the stated observation window. It does not, by itself, tell us how many total events occurred, how long an event lasted, how severe it was, or whether the same participant experienced more than one event. Those questions require different summaries. The primary outcome is specifically the number of participants with treatment-related TEAEs, not the total number of all adverse events.

The denominator also matters. The primary outcome population is the Safety Set, consisting of participants who received at least one dose of study drug. A count should be interpreted alongside the number of participants in its displayed group. Counts from groups of different sizes are not directly comparable by inspection alone, and even a proportion would not address differences in cohort design or follow-up. The registry record presents the group counts but does not post a formal comparison for this endpoint.

Why are the cohorts not one simple dose comparison?

In general, a dose-response interpretation depends on comparing groups that differ in dose while otherwise having a suitable, clearly described design. Here, the posted cohorts vary by dose, route, and single versus multiple dosing. Cohorts 1 to 6 have a stated primary-outcome timeframe of baseline up to Day 127, while Cohorts 8 to 9 have a timeframe of baseline up to Day 155. The registry record does not report an analysis that standardizes for these differences or tests a dose trend.

The cohort structure is sequential. In general, sequential dose studies can be designed to evaluate successive dose levels rather than to estimate a single pooled treatment contrast. The available registry description calls the model sequential, but details of cohort progression and the decision rules for moving between cohorts are not reported in the registry record. It would be inappropriate to infer those procedures from the cohort labels.

What is missing from the inferential results?

The registry reports no analyses for this record’s posted results summary. For the primary endpoint, it does not report a confidence interval, a p-value, a model-based estimate, or an adjusted comparison. A confidence interval, in general, expresses uncertainty around an estimate under a specified method; it does not make a small study precise merely by being calculated. A p-value, in general, assesses data under a stated null hypothesis and analysis, but it cannot be reconstructed from the counts without choosing assumptions and a method. No such analysis should be attributed to the registry record.

The sample-size section is a planning illustration based on an observed effect, not an observed-power calculation. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those are planning assumptions, not evidence about the trial’s original design. The registry record does not report the trial’s own sample-size justification. Because values are missing or not estimable for a two-arm comparison of this binary outcome, the posted primary endpoint does not support that comparison-based illustration.

How should uncertainty be understood?

In general, sparse counts can be compatible with a wide range of underlying event frequencies. Small groups make each participant’s outcome consequential to the displayed count, so apparent differences can reflect uncertainty as well as any underlying difference. A formal uncertainty interval can help communicate that imprecision when the analysis method and assumptions are specified. No such interval is reported for this endpoint, so the counts should remain descriptive.

Randomization and masking are features of the study design, but they do not automatically make every displayed group contrast valid. The analysis must correspond to the actual allocation and comparison structure. Here, active cohorts are listed separately and placebo is combined as All Placebo in the primary results. The registry record does not report the allocation details needed to reconstruct cohort-specific comparisons or an analysis plan that would justify combining or contrasting groups.

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("Cohort 1: ALXN1820 12.5 mg SC", "Cohort 2: ALXN1820 50 mg SC", "Cohort 3: ALXN1820 150 mg SC", "Cohort 4: ALXN1820 450 mg SC", "Cohort 5: ALXN1820 450 mg IV", "Cohort 6: ALXN1820 1200 mg SC")
n      <- c(5, 6, 5, 5, 5, 6)
events <- c(1, 0, 0, 4, 2, 0)
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  Cohort 1: ALXN1820 12.5 mg SC  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1
ARM  Cohort 2: ALXN1820 50 mg SC  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Cohort 3: ALXN1820 150 mg SC  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Cohort 4: ALXN1820 450 mg SC  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7
ARM  Cohort 5: ALXN1820 450 mg IV  5  2  40.0  5.3  85.3  11.8  76.9  11.8  77.7
ARM  Cohort 6: ALXN1820 1200 mg SC  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The study lists multiple objectives and outcomes, including safety, pharmacokinetics, pharmacodynamics, and immunogenicity. The registry record lists concentration measures and changes in total and free properdin among the secondary outcomes. When a study examines many outcomes or comparisons, multiplicity can affect how inferential findings are interpreted. In general, multiplicity procedures may control the chance of false-positive findings across a defined family of tests. The registry record does not report whether any such procedure was planned or used.

No statistical analyses are posted for the primary outcome, and the record does not report a multiplicity strategy, hierarchy of hypotheses, or prespecified family of comparisons. It is therefore not possible to determine how the study would treat multiple dose, route, or outcome comparisons in formal inference. The descriptive counts do not require an inferential multiplicity adjustment, but they also do not answer whether any broader collection of tests would have been adjusted.

The primary-outcome population is the Safety Set: all participants who received at least one dose of study drug. That definition is reported. The registry record does not report how missing endpoint status, incomplete follow-up, or participants without evaluable adverse-event data were handled. It also does not report imputation methods or sensitivity analyses for missing data. No assumption about complete follow-up or missingness should be made from the displayed counts alone.

The record names the number of participants enrolled, but it does not provide the trial’s sample-size justification or a statistical power calculation for the primary endpoint. The planning illustrations elsewhere on the page are not the trial’s design justification and are not observed power. The registry record also does not report a detailed analysis population beyond the Safety Set definition for this endpoint.

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 non-serious adverse event terms

The serious adverse-event summary reports zero serious adverse events in every displayed group. The groups are Cohorts 1 to 6, Cohorts 8 to 9, and All Placebo; the corresponding numbers at risk are 5, 6, 5, 5, 5, 6, 7, 6, and 15. The deaths column reports zero for each group. These figures describe what was recorded in the posted results for the groups and follow-up shown.

The registry defines a serious adverse event as an untoward medical occurrence meeting at least one serious criterion, such as resulting in death, being life-threatening, requiring inpatient hospitalization or prolongation of existing hospitalization, causing persistent or significant disability or incapacity, being a congenital anomaly or birth defect, or constituting another medically important serious event. The serious-event summary is distinct from the primary treatment-related TEAE endpoint: serious events are classified by seriousness, while the primary endpoint counts TEAEs assessed as treatment-related.

Zero recorded serious events does not establish that serious events cannot occur, nor does it provide a precise estimate of their frequency beyond these study groups and observation periods. The registry also reports nonserious adverse-event counts regardless of causality; those are a separate category and should not be conflated with the serious-event figures.

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

The registry results document the number of participants with treatment-related TEAEs in each displayed cohort, alongside separate serious and other adverse-event summaries. Those counts are the central descriptive findings for the primary endpoint. They allow readers to see how many participants met the endpoint definition during the specified follow-up in the Safety Set.

They do not, on their own, establish a causal difference between ALXN1820 and placebo. The active-treatment results are split across cohorts that differ by route, dose, and dosing schedule, whereas placebo is presented as one combined group. No formal two-arm comparison is reported. The counts also do not establish a dose-response relationship, particularly because the registry record does not report a statistical trend analysis or a prespecified comparison framework.

Nor do these results provide a complete account of safety. The primary outcome focuses on treatment-related TEAEs; the adverse-event summary separately reports serious and other events regardless of causality. Counts do not convey event severity, duration, recurrence, or clinical course. The registry record points readers to the reported adverse-event section for summaries, but the counts should not be expanded into claims that are not recorded.

The study was conducted in healthy participants and is described as a Phase 1 dose study. Its posted results therefore characterize the participants, regimens, event definitions, and follow-up represented in this record. They do not establish what would happen in another population or under other treatment conditions. The registry record does not report statistical uncertainty intervals for the primary endpoint, so the precision of any underlying event frequency cannot be quantified from a posted inferential analysis.

In short, the results are useful as a transparent descriptive record, with substantial limits on comparative interpretation. They should be read as counts in small, distinct cohorts rather than as proof of a treatment benefit, lack of benefit, or a definitive safety ranking.

14. Why This Trial Matters Statistically

This trial illustrates an important statistical distinction: a randomized and double-blind design does not mean every result displayed in a registry is a randomized comparison. The primary results are organized by separate dose cohorts, while placebo is shown as an All Placebo group. Without a posted analysis matching the comparison to the allocation structure, the counts remain descriptive rather than a dose-specific estimate of difference from placebo.

The study also shows why denominators and endpoint definitions matter. The primary endpoint is the number of participants with treatment-related TEAEs, whereas the other adverse-event summary includes nonserious events regardless of causality and separately records serious events. Those categories answer distinct questions. A reader who treats all event counts as interchangeable would misread the evidence.

Small cohort counts require restraint. In general, a count based on a small group can change noticeably when a participant’s status differs, and descriptive variation alone does not establish a systematic dose effect. Formal uncertainty estimates and a prespecified analysis can help frame comparisons, but neither is posted for this endpoint.

Finally, the record identifies the Safety Set and observation windows, which are essential to interpreting the outcome, while leaving important analytic details unreported. The trial’s own sample-size justification, missing-data handling, multiplicity plan, and detailed statistical analysis plan are not reported in the registry record. Distinguishing recorded results from undocumented procedures is part of sound statistical reading.

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 features limit interpretation of the posted primary endpoint. The active-treatment results are separated by cohort, and the regimens vary by dose, route, and single or multiple administration. The registry’s primary results place placebo in one All Placebo group rather than alongside each active cohort. The record does not report a cohort-specific comparison or an analysis addressing those structural differences.

The group sizes are small, and the endpoint is a count of participants with treatment-related TEAEs. The registry does not post confidence intervals or other measures of uncertainty for these counts. Consequently, the precision of the underlying event frequencies is not quantified by an inferential analysis. Counts should not be treated as definitive evidence of a difference or similarity among cohorts.

The observation windows differ: baseline up to Day 127 for Cohorts 1 to 6 and baseline up to Day 155 for Cohorts 8 to 9. The registry record does not report an analysis adjusting for differing follow-up or detail the handling of participants with incomplete observation. It also does not report event-level information in the primary count, such as duration or recurrence.

The registry record does not report the trial’s own sample-size justification, a detailed statistical analysis plan, a multiplicity approach, or missing-data methods. It does not report formal analyses for the primary endpoint. These absences mean the posted counts can be summarized, but the rationale and inferential framework behind any planned comparison cannot be reconstructed from this record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of ALXN1820 in Healthy Adult Participants — NCT04631562.
• Registry record last updated 2024-08-20; status last verified 2024-07.
• Results first posted 2024-03-15.
• 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

This is the completed Phase 1 randomized, double-blind, placebo-controlled study of ALXN1820 in healthy participants, listed as NCT04631562. The study evaluated single and multiple ascending SC doses and a single IV dose, with placebo administered SC or IV according to assigned cohort. Enrollment was 66; the study started on 2021-01-13 and had primary completion on 2022-09-01.

The primary outcome counts participants with treatment-related TEAEs in the Safety Set. Posted results are organized by active-treatment cohort and All Placebo, with separate serious and other adverse-event summaries. No statistical analyses are posted for the primary endpoint. The registry record does not report the trial’s sample-size justification, detailed statistical plan, missing-data methods, or multiplicity strategy.