A Study With TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study With TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc) (NCT04478994), a randomized phase 1 study. The primary outcome is Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE) Through Week 24.

2. Clinical Question

The trial asked whether TEPEZZA could be studied in participants with diffuse cutaneous systemic sclerosis (dcSSc), with objectives centered on safety and tolerability and on effects on IGF-1, inflammatory biomarkers, and fibrotic biomarkers. It also explored efficacy. The primary outcome counted participants experiencing a treatment-emergent adverse event (TEAE) from the first dose through Week 24.

3. Trial Design

The registry describes a phase 1, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Masking is listed as quadruple, but the registry record does not identify which parties were masked. The study title describes repeat dosing and safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy. The record lists Amgen as sponsor.

The study began on 2021-11-17, had a primary completion date of 2022-11-29, and is listed as terminated. A reason for termination is not reported in the registry record. The registry enrollment is 3. The primary outcome is specified for all randomized participants, and the posted arm counts for that outcome are 1 in the TEPEZZA group and 2 in the placebo group.

The arm descriptions are plans, not observed treatment exposure. The TEPEZZA arm is described as approximately 15 participants receiving eight infusions q3W, with 10 mg/kg on Day 1 and 20 mg/kg for the remaining seven infusions; the placebo arm is described as approximately 10 participants receiving eight placebo infusions q3W. Both descriptions give a total duration of 21 weeks. Separately, the brief summary describes TEPEZZA administration q3W for 24 weeks. The registry record does not explain the difference between these schedule descriptions. The posted outcome counts are much smaller than the approximate enrollment figures in the arm plans.

Randomization can help balance prognostic factors across groups in a sufficiently large study, while masking can reduce some forms of bias in treatment delivery and outcome assessment. These are general design principles; with the small posted group counts, balance and the practical effects of masking cannot be assessed from this record. Details such as the randomization procedure, allocation concealment, and specific masked roles 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE) Through Week 24, measured over From first dose of trial drug up to Week 24.

The primary endpoint is the number of participants experiencing a treatment-emergent adverse event (TEAE) from the first dose of trial drug up to Week 24. The registry defines an adverse event as an untoward medical occurrence that does not necessarily have a causal relationship with treatment. A TEAE is an event occurring after the first dose. Thus, the endpoint records occurrence after treatment begins, not proof that treatment caused the event.

This kind of endpoint is used to describe the safety experience during a specified observation period. Counting participants with an event gives a simple measure of how many people experienced at least one qualifying event; it does not count the total number of event episodes or distinguish event severity in the primary outcome. A participant with more than one event still contributes as a participant with an event for this count.

The posted outcome is 0 participants with a TEAE among 1 participant in the TEPEZZA group, and 2 among 2 in the placebo group. With so few observations, each participant has a substantial influence on the group count. The endpoint does not by itself establish comparative safety, explain the cause of an event, or describe all clinically relevant details. The registry lists serious and other adverse-event summaries separately, but does not post a comparative statistical analysis for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary outcome, each participant is classified according to whether the event occurred during the specified period. The primary endpoint is a count of participants with at least one TEAE. The posted count is 0 among 1 participant assigned to TEPEZZA 20 mg/kg and 2 among 2 assigned to placebo. These counts are not a model-based result: the registry record reports no analysis for the comparison. The record indicates that values were missing or not estimable for a two-arm binary comparison.

What does an event count capture?

An event count at the participant level answers whether a participant experienced at least one event, not how many separate events occurred. It also does not measure duration, severity, or the clinical relationship of an event to study treatment. The record’s definition is explicit that an adverse event does not necessarily have a causal relationship with treatment. “Treatment-emergent” describes when an event occurs relative to first dosing; it should not be read as an attribution of cause.

As a general statistical principle, binary outcomes can be compared using measures such as a difference in event proportions or a relative measure. Those estimates require sufficient information to support a meaningful comparison, and uncertainty is normally conveyed with a confidence interval. A confidence interval describes the range of effect values compatible with the data and the specified method; it is not a guarantee that the true effect lies within a particular interval. No comparative estimate or confidence interval is reported for this endpoint, and the registry indicates that the comparison is not estimable. No such result should be inferred from the raw counts.

Why does the small group size matter?

With very few participants, estimates of event frequency are unstable: the status of an individual can substantially affect the observed pattern. General statistical methods can quantify uncertainty, but any estimate based on these group counts would be imprecise. A lack of events in a small group is not evidence that the underlying event risk is zero. Conversely, events in a small group do not establish that the treatment caused them. The record does not provide a sponsor analysis to take precedence over a recalculation, and the binary comparison is explicitly not estimable.

Randomization is intended to support fair comparisons by allocating participants independently of expected outcomes. Its ability to balance participant characteristics is limited when groups are very small. The record says the study was randomized but does not report the sequence-generation method, allocation concealment, or baseline characteristics in the information available for this outcome. Masking is listed as quadruple; which individuals or roles were masked is not reported. The design labels alone cannot establish how well bias was controlled in practice.

What does a confidence interval add?

As a general concept, a confidence interval expresses statistical uncertainty around an estimate under a chosen method. Wider intervals indicate less precision, while narrower intervals indicate greater precision, all else equal. A confidence interval is not a test of clinical importance and cannot correct problems such as incomplete outcome reporting, selective availability of participants, or an unsuitable analysis. No confidence interval is posted for the TEAE comparison. Because the comparison is not estimable from the registry record, it is not appropriate to invent an interval or interpret the counts as a precise contrast.

The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those are assumptions for a planning illustration, not a reported trial design justification or an observed measure of power. The record also states that binary comparisons with missing or non-estimable values are skipped. Since the comparison is not estimable, no planning sample-size values should be inferred from the posted counts. The registry record does not report the trial’s own sample-size justification, a target effect, or an inferential analysis plan.

How should the other adverse-event summaries be read?

The registry separately reports serious adverse events and other adverse events by group. These summaries are also participant counts, with the group-specific numbers at risk shown in the safety reading. Seriousness is a classification distinct from whether an event was caused by treatment. The reported serious event term is Chronic lymphocytic leukaemia, listed at 50.0%; the record does not provide enough detail in the posted safety summary to establish attribution or to interpret that percentage as a comparative risk. These are descriptive safety observations, not a tested contrast.

Multiplicity concerns arise when investigators test several outcomes or contrasts, increasing the chance of at least one false-positive finding if no suitable approach is used. The registry lists one outcome measure and no posted analyses, but it does not report an analysis plan or any multiplicity procedure. It is therefore not possible to determine whether there were planned analyses beyond those appearing in the record or how multiple testing would have been handled. Absence of a posted procedure is not evidence that a particular procedure was or was not used.

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("TEPEZZA 20 mg/kg", "Placebo")
n      <- c(1, 2)
events <- c(0, 2)
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  TEPEZZA 20 mg/kg  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Placebo  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero posted analyses. The primary endpoint is the count of participants experiencing a TEAE through Week 24. No secondary outcome results are posted in the record. A formal testing hierarchy, adjustment for multiple comparisons, and the intended role of any exploratory analyses are not reported in the registry record. Without those details, it is not possible to assess a multiplicity strategy or determine whether the primary endpoint was the only outcome considered in the study.

Missing-data handling is also not reported in the registry record. The endpoint population is all randomized participants, but the record does not describe how missing outcome status, withdrawal, or incomplete follow-up was treated. The listed group counts show 1 participant in the TEPEZZA outcome group and 2 in placebo; the registry does not provide a separate account of participants with unavailable endpoint status or explain how the reported counts relate to any such cases.

Because the study is listed as terminated, readers may reasonably want to know whether termination affected recruitment, follow-up, or outcome availability. Those details, as well as the reason for termination, are not reported in the registry record. It would be inappropriate to infer that termination caused missing data or that any particular analysis population was used beyond the stated primary population of all randomized participants.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chronic lymphocytic leukaemia (50.0%).

For serious adverse events, the registry reports 0 affected participants among 1 at risk in the TEPEZZA 20 mg/kg group, and 1 among 2 at risk in the placebo group. The reported death count is 0 in each group. These are descriptive group counts; the registry record does not report a statistical comparison of serious adverse events.

For other adverse events, the registry reports 0 affected participants among 1 at risk in the TEPEZZA group and 2 among 2 at risk in the placebo group. “Serious” and “other” are separate categories in the registry summary. These figures should not be added together, since the summaries do not establish whether participants could appear in both categories. The overall safety summary also does not establish that an event was caused by treatment: the registry definition says an adverse event does not necessarily have a causal relationship with treatment.

The serious-event term listed is Chronic lymphocytic leukaemia at 50.0%. With the small group counts, this percentage represents a sparse observation and is not a stable estimate of risk. The record does not report enough detail to assess attribution, timing beyond the general safety period, or a comparative relationship. The event-term listing should not be interpreted as evidence that the intervention caused the condition.

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

The posted result establishes a narrow descriptive fact: the registry records 0 TEAEs among 1 participant in the TEPEZZA 20 mg/kg group and 2 among 2 participants in the placebo group through Week 24. The serious and other adverse-event summaries provide further counts, including a serious adverse event among 1 of 2 placebo participants at risk and none among the 1 TEPEZZA participant at risk. These numbers describe the small set of observations recorded, not a dependable estimate of how frequently events would occur in a broader population.

The result does not establish that TEPEZZA prevents adverse events, that placebo causes them, or that either group has a particular underlying risk. It does not establish a causal relationship between treatment and an event. The registry’s definition of an adverse event expressly allows events that are not causally related to treatment, while “treatment-emergent” identifies occurrence after first dose. Timing should not be mistaken for causation.

The result also does not answer the study’s broader questions about effects on IGF-1, inflammatory or fibrotic biomarkers, pharmacokinetics, pharmacodynamics, or efficacy. The registry record lists one outcome measure and no posted analyses. Results for these other objectives are not reported in the registry record. Nor does the primary TEAE count provide a full account of event severity, duration, recurrence, or clinical context.

The trial’s terminated status and small posted outcome groups limit the strength of any inference, but the registry does not give a reason for termination or explain how it affected the results. The approximate planned arm sizes are not the observed group counts and should not be treated as evidence that those planned numbers were reached. No comparative analysis is reported, and the registry marks the binary comparison as not estimable. Thus, the result is useful as a record of what was posted, but it cannot support a precise or causal conclusion about the comparative safety of the study regimens.

14. Why This Trial Matters Statistically

This study matters statistically because it illustrates the difference between a randomized trial design and an informative comparative result. Randomization, placebo control, and masking are design features intended to support valid comparisons. Yet the posted primary outcome counts involve only 1 participant in the TEPEZZA group and 2 in placebo. A rigorous design cannot by itself compensate for very sparse outcome data when estimating how groups differ.

The result also shows why event counts need context. The primary endpoint is a count of participants with at least one TEAE, not a causal assessment. The record’s definition distinguishes an event occurring after first dose from an event caused by treatment. Keeping that distinction clear is essential in safety reporting, especially where the number of observations is small and every participant’s experience strongly shapes the apparent pattern.

Another statistical lesson is the importance of matching interpretation to the available analysis. The registry marks a two-arm binary comparison as not estimable and posts no analyses. Reporting raw counts is informative about the record, but calculating a contrast and presenting it as a trial finding would go beyond what is documented. A planning illustration based on an observed effect is not a substitute for an estimable trial result, and it is not observed power.

Finally, the registry gives approximate planned group sizes that differ from the small posted outcome groups, and the study is marked terminated. Because the reason and consequences are not reported, readers cannot evaluate how recruitment or follow-up unfolded. This case therefore highlights the value of transparent reporting on participant flow, outcome availability, analysis methods, and termination. Without those details, even a clearly stated endpoint and randomized design leave substantial uncertainty about what comparative conclusions the trial can support.

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 immediate limitation is the small number of participants represented in the primary outcome counts: 1 in the TEPEZZA group and 2 in placebo. Such sparse data cannot characterize uncommon or variable safety outcomes with precision. The registry provides no confidence interval or comparative estimate, and explicitly indicates that the binary comparison is not estimable.

The status is terminated, but the reason for termination and its implications for recruitment, follow-up, and data availability are not reported in the registry record. The enrollment entry is 3, while the arm descriptions list approximate planned enrollment of 15 and 10. The record does not explain the difference. The planned figures should not be read as the number treated or analyzed.

Schedule descriptions also differ: the brief summary describes administration q3W for 24 weeks, while the arm descriptions specify eight infusions over 21 weeks. The registry record does not reconcile these statements. Details of actual exposure, adherence, dose interruptions, and treatment discontinuation are not reported in the registry record.

The record does not report baseline characteristics, a detailed participant flow, missing-outcome handling, the randomization method, or the statistical analysis plan. It lists no secondary outcome results and no posted analyses. Therefore, the primary safety counts cannot be placed in a full account of participant characteristics, follow-up completeness, or the study’s broader biomarker and exploratory efficacy objectives. The serious-event term listing is also too limited to determine causation or interpret the event clinically. These limitations restrict the result to a descriptive account of the posted observations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study With TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc) — NCT04478994.
• Registry record last updated 2024-06-28; status last verified 2024-06.
• Results first posted 2024-04-19.
• 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 randomized, double-blind, placebo-controlled, parallel-group phase 1 study of TEPEZZA in diffuse cutaneous systemic sclerosis, with quadruple masking listed. Amgen is the sponsor. The study began on 2021-11-17, has a primary completion date of 2022-11-29, and is listed as terminated. The registry enrollment is 3.

The primary outcome counts participants with a TEAE from first dose through Week 24. The posted counts are 0 among 1 participant for TEPEZZA 20 mg/kg and 2 among 2 participants for placebo. The registry reports no posted analyses and marks the binary comparison as not estimable. The reason for termination, missing-data procedures, and comparative statistical analysis are not reported in the registry record. The observed counts are descriptive and do not establish causation or a precise treatment comparison.