Safety and Efficacy of AMG 827 in Subjects With RA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of AMG 827 in Subjects With RA (NCT01059448), a na phase 2 study. The primary outcome is Number of Participants With a Treatment-emergent Adverse Event (TEAE).

2. Clinical Question

3. Trial Design

NCT01059448 is a phase 2, single-group extension study sponsored by Amgen. Its title describes a long-term assessment of subcutaneous AMG 827 in subjects with rheumatoid arthritis. The study was terminated. The registry lists a start date of 2010-06-03 and a primary completion date of 2011-04-05; it does not report why the study was terminated.

The extension was for participants in Protocol 20090061 (NCT00950989). The brief summary says participants would receive a 210 mg injection of AMG 827 for treatment of rheumatoid arthritis for up to 5 years. Arm descriptions specify administration at Day 1, Week 1, Week 2, and every other week thereafter. They also describe ongoing weekly methotrexate and folic acid or folate. The primary endpoint timeframe, however, is Day 1 to Week 52 of study 20090402. The registry does not report how the termination affected each participant’s actual time on treatment or follow-up.

Arm labels distinguish participants according to treatment in the parent study: placebo, 70 mg AMG 827, 140 mg AMG 827, or 210 mg AMG 827, followed by 210 mg AMG 827 in the extension. These histories are useful for understanding the groups reported in the safety record, but the study is registered as single group, with allocation listed as NA and no masking. The registry specifically cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Therefore, differences between their posted counts cannot be interpreted as randomized treatment effects.

Enrollment is listed as 211. The primary endpoint population is the FAS, defined as analyzable participants treated with at least one dose of AMG 827. The number included in each endpoint analysis is not reported in the registry record. The record lists 9 outcome measures and 0 analyses; it does not report a full statistical analysis plan or a sample-size justification.

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: 211 participants were enrolled and all 211 participants received study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS - All analyzable participants who were treated with at least one dose of AMG 827.

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) - All analyzable participants who were treated with at least one dose of AMG 827.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With a Treatment-emergent Adverse Event (TEAE), measured over Day 1 to Week 52 of study 20090402.

The primary endpoint is the number of participants with a treatment-emergent adverse event (TEAE), measured from Day 1 to Week 52 of study 20090402. The registry defines a TEAE as an event that began after the first dose and before the end of the study. It also includes an event already present at baseline if its frequency or severity worsened after the first dose and before the end of the study.

The endpoint definition additionally includes serious treatment-emergent adverse events, clinically significant changes from baseline in hematology, chemistry, and urinalysis profiles, and clinically significant changes in vital sign measurements. Thus, its scope is broader than a tally of newly reported symptoms alone. The outcome is a participant count, rather than a measure of event duration or severity on a continuous scale. The registry defines the population as the FAS: analyzable participants who received at least one dose of AMG 827.

In general, safety endpoints are used to describe the types and occurrence of potential harms during a specified period of exposure and observation. A treatment-emergent definition helps distinguish events that started after treatment from pre-existing events, while also recognizing worsening of existing conditions. It does not by itself establish that treatment caused an event. For this trial, the endpoint definition is reported, but an overall primary-endpoint count or other endpoint result is not reported in the registry record. The serious and other adverse event counts posted by group should therefore be read as distinct safety summaries, not as a complete reported result for the defined TEAE endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event measure: a participant either meets the TEAE definition during the stated timeframe or does not. The registry describes the outcome as a count of participants. This is different from counting every event episode, because a participant with more than one event may still contribute as a participant with an event rather than as multiple people. The record does not provide further rules for counting repeated events within a participant.

What does the endpoint definition capture?

The definition uses a temporal rule tied to the first dose and end of study. It also counts a pre-existing event if it worsens in frequency or severity after dosing begins. In general, this approach is intended to summarize events emerging or worsening during treatment and observation. It does not prove that treatment caused an event: events can occur for other reasons, and the registry record does not describe a causal-adjudication method. The endpoint also includes serious treatment-emergent events and specified clinically significant changes in laboratory profiles and vital signs, so its scope includes more than reports of symptoms.

How should counts and denominators be read?

For the posted adverse event summaries, each group has an at-risk count and an affected-participant count for serious events and for other events. Those counts describe the recorded experience in the group. They are not themselves estimates adjusted for differences in exposure time, baseline characteristics, or follow-up. The registry does not report person-time, duration-specific event rates, adjustment methods, or uncertainty intervals for these counts. A count of affected participants should not be assumed to equal a count of all event episodes.

In general, a confidence interval expresses uncertainty around an estimated quantity under stated assumptions. It can help readers distinguish a relatively precise estimate from one compatible with a wide range of values. No confidence interval for the primary endpoint or the posted adverse event counts is reported in the registry record. A p-value is also not reported for a comparison of these counts. Without a reported inferential analysis, descriptive differences among group counts do not establish statistical evidence of a difference.

What do the design and allocation imply?

The study is identified as single group, with allocation listed as NA and masking as none. Arm labels reflect prior regimens in the parent study followed by the same described extension regimen. Since the registry cautions that this is not a randomized comparison and the groups are not like-for-like controls, a direct between-group causal contrast is not justified by the record. In general, random allocation can help balance measured and unmeasured characteristics at baseline; the record does not establish that this occurred for the extension arms.

What is reported about planning calculations?

The registry describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the stated illustration concerns a total number of events using the Schoenfeld method; for other outcomes, it concerns participants per arm. These are planning illustrations, not observed power. The numerical illustrations are not reported in the registry record, and the record does not report the trial’s own sample-size justification or establish that these assumptions were used to design or conduct the study.

In general, a sample-size calculation estimates how much information a future study would need under specified assumptions. It is not a measure of the probability that an already completed result is correct. Calculations anchored to an observed effect may also depend strongly on that effect’s estimate and on the chosen fraction. No new sample-size calculation or recalculation is reported for this study.

What model or analysis was used?

The registry lists 0 analyses. A model, adjustment set, hypothesis test, confidence-interval method, and detailed statistical analysis plan are not reported in the registry record. It is therefore not possible to attribute the posted counts to a specified statistical model or to determine whether any unreported analysis adjusted for baseline differences. General statistical methods cannot fill that reporting gap. In particular, the reported binary counts should remain descriptive unless an analysis method and a suitable comparison are documented.

Over-dispersion is a concern in some count-data models when variability exceeds what a chosen model assumes; in general, that can make standard errors too small if ignored. It is not possible to assess over-dispersion from these participant-level adverse event counts alone, and the registry does not report a count-data model. More fundamentally, the primary outcome is specified as the number of participants with an event, not the total number of event episodes. No claim about an over-dispersion adjustment can be made from the registry record.

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("Placebo Q2WK / 210 mg AMG 827 Q2WK", "70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK", "140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK", "210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK")
n      <- c(49, 55, 53, 54)
events <- c(28, 32, 31, 32)
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  Placebo Q2WK / 210 mg AMG 827 Q2WK  49  28  57.1  42.2  71.2  43.3  70.0  43.2  70.0
ARM  70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK  55  32  58.2  44.1  71.3  45.0  70.3  45.0  70.3
ARM  140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK  53  31  58.5  44.1  71.9  45.1  70.7  45.0  70.8
ARM  210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK  54  32  59.3  45.0  72.4  46.0  71.3  45.9  71.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures but 0 analyses. It does not report a statistical analysis plan explaining which outcomes were confirmatory, how they were prioritized, or whether hypothesis tests were planned. A procedure for handling multiplicity is not reported in the registry record. In general, when several outcomes or comparisons are tested, multiplicity matters because the chance of at least one apparently unusual result can increase. Without a stated testing strategy and reported inferential results, the posted descriptive counts should not be read as confirmatory evidence.

The primary endpoint population is defined as the FAS, consisting of analyzable participants treated with at least one dose of AMG 827. The record does not report the number analyzed for the primary endpoint, exclusions from that population, or how incomplete endpoint information was handled. Missing-data rules, imputation methods, and sensitivity analyses are not reported in the registry record. These details matter because incomplete follow-up or missing safety assessments can affect who contributes to an endpoint count and what period of risk is represented.

The registry reports group-specific at-risk counts for the serious and other adverse event summaries, but those figures do not provide a full account of missingness or follow-up. The number of participants with unobserved endpoint status, reasons for missing data, and any assumptions about missing observations are not reported in the registry record. A reader cannot determine from the counts alone whether participants had comparable observation periods or whether all relevant assessments were available.

Enrollment is listed as 211, but the registry does not equate that figure with the analyzed population for the primary endpoint. In general, enrollment, treatment exposure, and analysis populations can differ. The reported definition of the FAS clarifies who should be eligible for that analysis, while the absence of endpoint-level analysis details limits assessment of how that definition was applied.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: chest pain (2.0%), hypersensitivity (2.0%), pneumonia (2.0%), osteoarthritis (1.9%), dysphagia (1.8%).

The registry gives serious adverse event and other adverse event counts separately for groups defined by parent-study regimen followed by the extension regimen. In the Placebo / AMG 827 210 mg Q2WK group, the serious-event count is 2 among 49 at risk, and the other-event count is 15 among 49 at risk. The 70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK group has counts of 5 among 55 at risk and 18 among 55 at risk, respectively. The 140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK group has counts of 1 among 53 at risk and 19 among 53 at risk. The 210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK group has counts of 0 among 54 at risk and 22 among 54 at risk.

These figures identify participants recorded as affected within each category; they should not be added together, treated as event-episode totals, or interpreted as comparative risks. The registry warns that this is not a randomized comparison, and differences in observation or participant characteristics may matter. The deaths field is not reported in the registry record. Serious-event terms are listed with percentages, but their denominator and calculation method are not reported in the registry record. The figures therefore support a descriptive reading, not a causal or comparative safety conclusion.

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

The registry record establishes that the study was an extension assessment of AMG 827 in rheumatoid arthritis and that the primary endpoint was defined as the number of participants with a TEAE over Day 1 to Week 52 of study 20090402. It also defines what qualifies as a TEAE, including events that began after the first dose, worsening baseline events, serious events, and specified clinically significant laboratory or vital sign changes. These details clarify the safety question the endpoint was intended to address.

The posted results include group-specific counts of participants at risk and affected by serious and other adverse events. They show that the record contains safety observations across the parent-regimen groups. They do not provide a reported overall count for the defined primary TEAE endpoint. Nor do the counts identify which event was attributed to AMG 827, how long each participant was observed, or whether groups differed in relevant baseline features. The registry does not report a statistical analysis comparing the groups.

The record therefore cannot establish from these figures alone whether AMG 827 caused a particular event, whether its safety profile differs from another treatment, or whether an apparent difference among groups is more than descriptive variation. The extension has no like-for-like randomized control comparison according to the registry’s own caution. The posted counts are also not equivalent to event rates adjusted for time at risk, and the listed percentages for serious-event terms have no reported denominator or calculation description.

The result should be understood as a limited registry account of safety categories and counts, alongside a defined but unreported primary endpoint result. The study status is terminated, but the reason for termination and its implications for observation are not reported in the registry record. In general, absence of a reported result is not evidence that no events occurred, and a count of events is not by itself evidence of treatment causation. The record supports cautious description, not a treatment recommendation or a definitive comparative conclusion.

14. Why This Trial Matters Statistically

This trial illustrates why study design and endpoint reporting matter when interpreting clinical safety data. The study evaluates an extension regimen in participants from a parent study, but the registry identifies the extension as single group and lists allocation as NA. Although results are grouped by the parent-study regimen, that history does not turn the extension into a randomized comparison. The registry explicitly cautions that the arms are not like-for-like controls. Recognizing that distinction prevents descriptive group counts from being mistaken for causal treatment effects.

The endpoint definition also shows why precision in outcome language matters. A TEAE includes events that arise after treatment starts and pre-existing events that worsen, alongside serious events and specified clinically significant test or vital-sign changes. The endpoint is broader than a simple tally of new symptoms. Yet the registry does not report the overall result for this primary endpoint. The available serious and other adverse event counts answer narrower descriptive questions and cannot fill that reporting gap.

The record further demonstrates that counts need context. At-risk counts accompany the posted affected-participant counts, but the registry does not report exposure time, missing-data handling, endpoint-level analysis details, or uncertainty intervals. Without such information, readers cannot establish whether differences reflect exposure duration, participant mix, chance variation, or other factors. The listed serious-event percentages also lack a reported denominator and method.

For biostatistical interpretation, the key lesson is to separate a defined estimand from the result actually reported, and to separate safety description from causal comparison. The study’s enrollment figure and FAS definition answer different questions; enrollment is not a substitute for the number analyzed. The record’s 0 analyses and absence of a reported statistical plan also limit assessment of multiplicity, modeling, and inferential uncertainty. These distinctions are essential for reading extension-study evidence without overstating what the record establishes.

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 record. First, the primary TEAE endpoint is defined, but its overall result is not reported in the registry record. The available adverse event counts are categorized as serious and other events, and should not be presented as the complete primary endpoint result. The registry lists 9 outcome measures and 0 analyses, and does not report a statistical analysis plan, endpoint-specific analysis methods, or inferential comparisons.

Second, this is a single-group extension study with allocation listed as NA and masking as none. The groups retain parent-study treatment labels, but the registry warns that they are not a like-for-like control comparison. The group counts therefore do not support a randomized causal contrast. The registry does not report an explanation for study termination or how termination affected the amount of follow-up each participant received.

Third, the record does not report the number included in each primary endpoint analysis, the extent or reasons for missing data, or methods for handling missing observations. It defines the FAS as analyzable participants treated with at least one dose, but does not show how that definition was applied to the primary outcome. Exposure duration and person-time are not reported for the safety counts, limiting rate-based interpretation.

Finally, deaths are not reported in the registry record, and the denominator and calculation method for the listed serious-event percentages are not reported. Baseline group characteristics, adjusted analyses, confidence intervals, and p-values for safety comparisons are also not reported in the registry record. These limitations restrict the conclusions to cautious description of the listed counts and the endpoint definition.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of AMG 827 in Subjects With RA — NCT01059448.
• Registry record last updated 2022-02-28; status last verified 2022-01.
• Results first posted 2022-02-28.
• 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

NCT01059448 is a terminated phase 2 extension study sponsored by Amgen, assessing subcutaneous AMG 827 in participants with rheumatoid arthritis who participated in Protocol 20090061 (NCT00950989). The registry lists enrollment as 211, a start date of 2010-06-03, and a primary completion date of 2011-04-05. The study is registered as single group, with allocation listed as NA and masking as none.

The primary endpoint is the number of participants with a TEAE from Day 1 to Week 52 of study 20090402. The endpoint definition includes newly occurring events, worsening baseline events, serious events, and specified clinically significant laboratory and vital sign changes. The overall primary endpoint result is not reported in the registry record. Group-specific serious and other adverse event counts are posted, but the registry cautions against treating the groups as a like-for-like control comparison. It lists 9 outcome measures and 0 analyses; the analysis plan, missing-data methods, reason for termination, and deaths are not reported in the registry record.