This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia Study (NCT02593773), a na phase 3 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02593773 |
| Phase | Phase 3 |
| Condition | Friedreich's Ataxia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 86 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned children and young adults with Friedreich's Ataxia who entered an open-label extension. The safety population was defined as participants who received at least one dose of open-label study drug after the Baseline Visit. The adverse-event results list 86 participants at risk for both serious and other adverse events.
Intervention
Participants received ACTIMMUNE® (interferon γ-1b) by subcutaneous injection three times weekly for 26 weeks. The stated purpose of the phase 3, multicenter extension was to evaluate long-term safety. The registry record describes an open-label study, so treatment was not masked.
Comparator
There was no concurrent comparator group. The study is registered as a single-group study, with allocation listed as not applicable. It therefore does not provide a like-for-like randomized comparison against placebo, usual care, or another treatment.
Primary question
The primary safety outcome counted participants with treatment-emergent adverse events, serious adverse events, and discontinuations due to adverse events. The registry record defines adverse events broadly, whether or not they were considered related to study drug. The posted safety figures include 4 participants with serious adverse events, but do not report the primary outcome’s complete set of category-specific results.
3. Trial Design
This was a phase 3, multicenter, open-label extension study of ACTIMMUNE® (interferon γ-1b) in children and young adults with Friedreich's Ataxia. The registered study model is single group, and allocation is listed as not applicable. Masking is listed as none. Accordingly, the design describes exposure to study drug and follow-up rather than a randomized comparison between treatment groups.
The registry record lists enrollment of 86. The intervention was subcutaneous ACTIMMUNE® three times weekly for a total of 26 weeks. The study began on 2015-12-25 and primary completion was recorded as 2017-03-21; its status is completed. The study's stated purpose was to evaluate long-term safety.
The primary safety timeframe runs from Baseline/Day 1, described as Week 26 of study HZNP-ACT-301 (NCT02415127), through Week 28, the follow-up safety visit. The safety population includes participants who received at least one dose of open-label study drug after the Baseline Visit. The adverse-event results list 86 participants at risk in the interferon γ-1b group.
Secondary outcomes included changes in Activities of Daily Living score, the Timed 25-Foot Walk, and total Friedreich Ataxia Rating Scale score, as well as the number of FARS-mNeuro responders and non-responders at Week 26. The registry record does not report a concurrent control group or an allocation procedure that would support a controlled treatment comparison. Its findings should therefore be read as descriptive results from an open-label, single-group extension.
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
| Stage | Interferon γ-1b |
|---|---|
| STARTED | 86 |
| COMPLETED | 51 |
| NOT COMPLETED | 35 |
Reasons for not completing this period:
| Reason | Interferon γ-1b |
|---|---|
| Voluntary Withdrawal | 3 |
| Study Terminated by Sponsor | 31 |
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety Population, defined as all participants who received at least 1 dose of open-label study drug after the Baseline Visit.
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.
| Characteristic | Unit | Interferon γ-1b |
|---|---|---|
| Participants analysed | 86 | |
| Age, Continuous | years | 16.8 (SD 4.05) |
| Sex: Female, Male: Female | Participants | 49 |
| Sex: Female, Male: Male | Participants | 37 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 82 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 81 |
| Race (NIH/OMB): More than one race | Participants | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs, measured over Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint concerns the number of participants with treatment-emergent adverse events, serious adverse events, and discontinuations due to adverse events. It is a safety endpoint, not a measure of change in Friedreich's Ataxia symptoms or function. The registry record defines an adverse event as an untoward medical occurrence, whether or not it is considered related to the investigational product. A treatment-emergent adverse event is an adverse change from baseline, including a clinically significant laboratory abnormality judged by the investigator, occurring on or after the first dose and during the study.
A serious adverse event is defined by consequences such as death, a life-threatening event, persistent or significant disability, inpatient hospitalization or its prolongation, a congenital anomaly or birth defect, or another medically important event. These definitions distinguish seriousness from whether an event was judged treatment-related: the record’s definition does not require a causal relationship.
Counting affected participants is useful for describing how many people experienced events in the stated categories. It does not, by itself, describe event duration, severity within a category, recurrence, or causal attribution. The primary endpoint title names three categories, but complete category-specific results for treatment-emergent adverse events and discontinuations due to adverse events are not reported in the registry record. The posted figures should not be treated as a single combined count or added to produce a total number of people, because category overlap is not reported.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registered study is a single-group, open-label extension, not a randomized comparative trial. The posted results are therefore descriptive safety observations during interferon γ-1b exposure and follow-up. They do not estimate a difference against an untreated or comparator group, and cannot separate events occurring during follow-up from events that would have occurred without study drug.
The adverse-event results list 86 participants at risk in the interferon γ-1b group. Within those results, 4 participants are listed as having serious adverse events, and 66 are listed under other adverse events. The registry record also lists 1 death. The record does not establish that the death or any adverse event was caused by treatment. Nor does it report enough detail to infer the timing, duration, clinical course, or relationship to treatment for each event.
The serious-event terms listed include Chest pain (2.3%), Atrial fibrillation (1.2%), Cardiogenic shock (1.2%), Eosinophilic myocarditis (1.2%), Sepsis (1.2%), and Chest injury (1.2%). These are term-specific percentages as recorded. The record does not provide a complete account of how terms relate to individual participants, and these term entries should not be summed to estimate a number of people. A participant may have more than one event term; the extent of overlap is not reported.
The primary outcome includes treatment-emergent adverse events, serious adverse events, and discontinuations due to adverse events. Although serious and other adverse-event counts are posted, the record does not report complete results for all named primary categories. In particular, it does not report a count for discontinuations due to adverse events in the registry record for this analysis. It is therefore not possible to reconstruct a complete primary-endpoint result from the posted safety figures.
Precision is also difficult to assess. No confidence intervals or inferential analyses are reported in the registry record. A confidence interval, in general, describes a range of values compatible with the data under a statistical procedure; without one, the counts do not quantify uncertainty around an underlying event frequency. The group counts remain useful as a factual description of events recorded in this study, but they should not be interpreted as a comparative estimate or a definitive measure of risk.
9. Statistical Methods Explained
The main statistical feature is the single-group design. Participants received the study intervention, and the posted safety outcomes describe events during the specified study period. Without a concurrent comparator, the analysis is not a randomized estimate of the difference between treatment strategies. General statistical interpretation: an observed event count can describe what was recorded in a study group, but it cannot by itself show what would have happened to the same participants under a different treatment or without treatment.
What does a participant count represent?
The primary outcome is expressed as a number of participants with events in named safety categories. A participant count is different from an event count: a person could experience more than one event, while a count of people with an event ordinarily counts that person once within the relevant category. The registry record does not report event-level detail or category overlap, so counts from separate categories should not be added to create a total number of affected participants. The 4 participants listed with serious adverse events and the 66 listed with other adverse events are separate posted results; the record does not clarify whether any individuals appear in both categories.
The primary endpoint title also includes treatment-emergent adverse events and discontinuations due to adverse events. The available registry results do not state the full count for each named primary category. Consequently, no complete composite or overall safety count can be reconstructed. General statistical principle: outcome definitions and category boundaries matter because seemingly similar labels may use different event rules, time windows, or units of counting.
Why does the absence of a control group matter?
In a randomized comparison, treatment groups can support a direct estimate of how outcomes differ between assigned strategies, subject to the design and analysis assumptions. Here, allocation is listed as not applicable and the model as single group. The observed counts therefore describe the study experience, not a treatment contrast. They cannot establish whether the frequency of an event was higher or lower than it would have been under another strategy.
The open-label design also means treatment was not masked. This is relevant to interpretation because event recognition, reporting, and decisions about whether an event is clinically significant can involve judgment. The registry definition specifies that clinically significant laboratory abnormalities are judged by the investigator. The record does not report procedures that would allow assessment of how ascertainment was standardized or whether event review was independently blinded.
How should uncertainty be understood?
Counts alone do not show how precisely an underlying event rate is estimated. General statistical explanation: a confidence interval expresses uncertainty around an estimate under a chosen method, while a hypothesis test evaluates compatibility with a specified null model. Neither confidence intervals nor inferential results are reported in the registry record. No p-values or adjusted treatment comparisons are available in the registry record.
The planning assumptions recorded for sample-size illustrations are not the study's own design justification. They describe two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. The registry record does not report the trial's sample-size justification. Such planning illustrations are hypothetical calculations, not observed power, and do not transform this single-group extension into a two-arm comparison.
For event data, the underlying event probability and follow-up period are important to interpretation. General statistical principle: sparse events can produce substantial uncertainty, and percentages may look precise even when the event count is small. Here, the registry reports selected term percentages but no confidence intervals for them. They should be read as descriptive entries, not as precise comparative estimates.
The record lists secondary outcomes involving function, walking performance, and rating-scale scores. It does not report analysis entries for these outcomes in the registry record. Their inclusion as planned or registered outcomes does not establish that results were posted, nor does it reveal the statistical model, baseline adjustment, or handling of repeated measures. Those analysis details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists multiple secondary outcomes, including Activities of Daily Living score, Timed 25-Foot Walk, FARS-mNeuro responder status, and total Friedreich Ataxia Rating Scale score. The available record does not report analysis entries for these outcomes. It also does not report a multiplicity strategy, such as whether statistical testing across outcomes would be adjusted or whether any outcome was designated for formal hypothesis testing beyond the primary safety endpoint. Without those details and results, the secondary outcome list should not be read as a set of confirmed statistical findings.
Missing-data procedures are not reported in the registry record. There is no stated approach to missing outcome measurements, incomplete follow-up, or participants who discontinued. The registry entries do not identify whether any missing observations occurred or how they were handled. General statistical principle: missingness can affect estimates when the likelihood of having an observed measurement is related to health status, treatment exposure, or the outcome itself; an analysis method and assumptions are needed to assess that issue.
The safety population is defined as all participants who received at least one dose of open-label study drug after the Baseline Visit. The adverse-event results list 86 participants at risk. The registry record does not provide a separate analysis population for each secondary outcome or details of how participants with incomplete measurements were included. It also does not report a protocol-level analysis plan or a description of interim analyses. These omissions limit assessment of how consistently outcome-specific analyses followed prespecified rules.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Interferon γ-1b | 4 | 86 | 4.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Interferon γ-1b | 1 of 86 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Interferon γ-1b | 66 of 86 |
Most frequent serious adverse event terms
| Event term | Organ system | Interferon γ-1b |
|---|---|---|
| Chest pain | General disorders | 2 of 86 |
| Atrial fibrillation | Cardiac disorders | 1 of 86 |
| Cardiogenic shock | Cardiac disorders | 1 of 86 |
| Eosinophilic myocarditis | Cardiac disorders | 1 of 86 |
| Sepsis | Infections and infestations | 1 of 86 |
| Chest injury | Injury, poisoning and procedural complications | 1 of 86 |
| Heart rate increased | Investigations | 1 of 86 |
| Haemodynamic instability | Vascular disorders | 1 of 86 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Interferon γ-1b |
|---|---|---|
| Headache | Nervous system disorders | 25 of 86 |
| Neutropenia | Blood and lymphatic system disorders | 18 of 86 |
| Pyrexia | General disorders | 15 of 86 |
| Nausea | Gastrointestinal disorders | 13 of 86 |
| Vomiting | Gastrointestinal disorders | 13 of 86 |
| Cough | Respiratory, thoracic and mediastinal disorders | 13 of 86 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 11 of 86 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 9 of 86 |
| Dizziness | Nervous system disorders | 8 of 86 |
| Fatigue | General disorders | 7 of 86 |
Serious events with the highest arm-level rate: chest pain (2.3%), atrial fibrillation (1.2%), cardiogenic shock (1.2%), eosinophilic myocarditis (1.2%), sepsis (1.2%).
The posted safety figures list 4 participants with serious adverse events among 86 at risk in the interferon γ-1b group. Seriousness is defined by the consequences of an event, including death, life-threatening events, hospitalization, significant disability, congenital anomaly or birth defect, or another medically important event. The registry record also lists 66 participants under other adverse events and 1 death.
The event-term entries include Chest pain (2.3%), Atrial fibrillation (1.2%), Cardiogenic shock (1.2%), Eosinophilic myocarditis (1.2%), Sepsis (1.2%), and Chest injury (1.2%). These percentages are reported for terms, not as a complete summary of all serious-event experience. The registry record does not explain the overlap between terms or give details for each individual event. Term entries should not be summed to infer a number of participants.
The figures describe events recorded in the study; they do not establish that an event was caused by interferon γ-1b. The record does not provide causal attribution for the listed events, nor does it report the cause of the death. The total count of all treatment-emergent adverse events and the number of discontinuations due to adverse events are not reported in the registry record. These limitations mean the serious-event count is a partial safety description rather than a complete account of the primary endpoint.
12. What the Result Does, and Does Not, Mean
The results establish that the registry records serious adverse events, other adverse events, and a death during the open-label extension. Specifically, the interferon γ-1b group has 4 participants listed with serious adverse events and 66 listed with other adverse events, with 86 participants at risk; the record also lists 1 death. The serious-event terms and percentages provide additional descriptive detail about events entered in the record.
These observations do not establish that treatment caused the events or that the treatment changed the risk of events. The study has no concurrent comparator group, and it is open label. Differences from an external population or from expectations would not constitute a randomized comparison. The record also does not supply enough detail to estimate a causal effect or to assess whether particular events were treatment-related.
The results do not provide a complete numerical account of every category named in the primary outcome. Treatment-emergent adverse-event and discontinuation results are not fully reported in the registry record. Nor are event-level details, uncertainty intervals, or inferential analyses reported. The posted counts should therefore be treated as descriptive, with the listed denominator and time window in mind, rather than as precise estimates that can be compared directly with another study.
General statistical interpretation: a safety count is most informative when its population, observation period, event definition, and method of ascertainment are clear. The registry supplies definitions and a follow-up window, but not all analysis details needed to judge missing data, overlap among categories, or uncertainty. The secondary outcomes do not add evidence to the safety interpretation because their analysis results are not reported in the registry record.
Thus, the study documents safety events during a defined open-label extension, but its single-group design and incomplete outcome reporting restrict what can be inferred beyond those recorded observations. It does not provide a controlled estimate of benefit or harm, nor a basis for attributing a particular event to treatment.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between describing events and estimating a treatment effect. In a single-group extension, counts can characterize what was recorded among participants receiving study drug, but there is no randomized comparison to indicate how those counts differ from an alternative strategy. The open-label design and absence of a concurrent control define the limits of interpretation before any individual event count is considered.
The registry record also illustrates why endpoint labels and outcome reporting need to be read together. The primary safety endpoint names treatment-emergent adverse events, serious adverse events, and discontinuations due to adverse events. The posted figures include serious and other adverse-event counts, but do not provide complete results for all named categories. A reader cannot responsibly fill those gaps by treating one reported count as a substitute for another.
Safety reporting also involves distinctions between participants and events, and between an event's seriousness and its relationship to treatment. The record defines seriousness by clinical consequences and defines adverse events regardless of whether they are considered related to the investigational product. The listed serious-event terms add context, but do not establish causation or give a complete person-level account.
Finally, the registry does not report uncertainty intervals, inferential analyses, missing-data methods, or a multiplicity strategy for secondary outcomes. These are not merely technical details: they affect how precisely results can be interpreted and whether multiple outcomes support formal claims. The study's value as a descriptive safety record is separate from its ability to support comparative or causal conclusions, which the available single-group data do not provide.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The central limitation is the single-group, open-label design. Allocation is listed as not applicable, masking as none, and no concurrent comparator is reported. The safety counts therefore cannot show how outcomes compare with another treatment strategy or what would have happened without study drug. A causal treatment effect is not estimable from these posted counts alone.
Outcome reporting is incomplete relative to the title of the primary endpoint. The registry record includes counts for serious and other adverse events, but does not report complete results for treatment-emergent adverse events and discontinuations due to adverse events. It also does not report a full event-level account, the cause of the death, or causal attribution for the listed adverse events. The relation between serious-event terms and individual participants is not described.
The record does not report confidence intervals, p-values, or other inferential analyses. It does not report missing-data handling, an analysis plan, a multiplicity procedure, or interim-analysis details. These omissions limit assessment of precision, outcome selection, and potential effects of incomplete follow-up. The secondary outcomes are named, but their results and analysis methods are not reported in the registry record.
The safety population definition applies to participants who received at least one dose after the Baseline Visit, and the adverse-event results list 86 at risk. The registry does not provide further detail about exposure duration for individual participants or variation in follow-up. The specified primary timeframe extends through Week 28, but the posted counts alone do not show whether every participant contributed the same observation time. No conclusion about comparative event rates or treatment causation should be drawn from that information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia Study — NCT02593773.
- Registry record last updated 2024-12-19; status last verified 2024-11.
- Results first posted 2018-05-18.
- 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.
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18. Record Summary
NCT02593773 is a completed phase 3, multicenter, open-label extension study of ACTIMMUNE® (interferon γ-1b) in children and young adults with Friedreich's Ataxia. It is registered as a single-group study, with no masking and allocation listed as not applicable. The intervention was subcutaneous dosing three times weekly for 26 weeks. Enrollment was 86, and the study's stated purpose was long-term safety evaluation.
The primary safety outcome concerned treatment-emergent adverse events, serious adverse events, and discontinuations due to adverse events. The adverse-event results list 4 participants with serious adverse events, 66 with other adverse events, and 1 death; 86 participants are listed at risk. The registry record does not report complete results for every category named in the primary endpoint, causal attribution, uncertainty intervals, or inferential analyses.
Secondary outcomes included functional and rating-scale measures at Week 26, but their analysis results are not reported in the registry record. The single-group design supports descriptive safety reporting, not a controlled estimate of treatment effect.