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 Use of ACTIMMUNE in Patients With ADO2 (NCT02584608), a na phase 2 study. The primary outcome is Changes in Bone Resorption Markers From Baseline to 14 Weeks..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02584608 |
| Phase | Phase 2 |
| Condition | Autosomal Dominant Osteopetrosis Type 2 |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Indiana University |
| Results posted | Yes |
2. Clinical Question
Population
Patients with autosomal dominant osteopetrosis type 2 (ADO2) were eligible for the study. The registry lists 12 participants enrolled and describes recruitment from Indiana University and Riley Hospital for Children at Indiana University Health. The primary outcome population is identified as all subjects; further eligibility details and participant characteristics are not reported in the registry record.
Intervention
The study evaluated ACTIMMUNE, also described as interferon gamma-1b. The treatment description specifies 50 µg/m2 administered subcutaneously three times per week for 8 weeks. The brief summary says treatment effects would be evaluated after 14 weeks on ACTIMMUNE; the relationship between this assessment timing and the stated treatment duration is not explained further in the registry record.
Comparator
There was no separate control group. The study is listed as single group, open label, and without a randomized allocation. Its planned comparison is therefore a change in bone-resorption markers from baseline to follow-up within the treated group, not a direct contrast between ACTIMMUNE and another treatment or no treatment.
Primary question
The primary outcome asks how bone-resorption markers changed from baseline to 14 weeks. The specified markers are CTX and the NTX/creatinine ratio, with change expressed as a percentage and summarized by a mean and full range. Numerical results for this outcome are not reported in the registry record. Consequently, the record describes the question the study set out to examine but does not show the observed marker changes or their precision.
3. Trial Design
This completed Phase 2a study evaluated ACTIMMUNE in patients with ADO2. The registry describes an open-label, single-group design, with no randomized allocation and no separate control arm. The enrollment was 12. Indiana University is listed as the sponsor. The record gives a study start date of 2016-01-01 and a primary completion date of 2019-11-12.
The treatment description specifies ACTIMMUNE 50 µg/m2 subcutaneously three times per week for 8 weeks. The brief summary describes assessment of treatment effects after 14 weeks on ACTIMMUNE. The primary outcome is a baseline-to-14-week change in bone-resorption markers. A secondary outcome describes change in bone-turnover markers after completion of 6-12 weeks of treatment. Details about the timing of individual assessments, adherence, dose changes, or reasons for discontinuation are not reported in the registry record.
Because all participants were in the treatment group, the study can describe changes observed during follow-up among enrolled participants, but it cannot directly compare those changes with an untreated or separately treated group. Open-label status means the study was not masked. The registry record does not report a protocol rationale for these design choices, a 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.
Overall Study
| Stage | Treatment |
|---|---|
| STARTED | 12 |
| COMPLETED | 12 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All subjects
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 | Treatment |
|---|---|---|
| Participants analysed | 12 | |
| Age, Categorical: <=18 years | Participants | 3 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous: Total | years | 30.48 (8.1 to 50.8) |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 12 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| 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 | 1 |
| Race (NIH/OMB): White | Participants | 11 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Changes in Bone Resorption Markers From Baseline to 14 Weeks., measured over baseline, 14 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | percentage of change |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint concerns percentage change in bone-resorption markers from baseline to 14 weeks. The markers named in the registry are CTX and the NTX/creatinine ratio. CTX and NTX are indicators used to assess bone resorption; the creatinine ratio expresses NTX relative to creatinine. The registry specifies a mean and full range as the summaries for this outcome, and identifies all subjects as the outcome population.
In general, measuring a marker at baseline and again during follow-up provides a way to describe how that laboratory measure changes over time within participants. Such markers can be useful for studying biological processes related to bone turnover. A marker change is not, by itself, a direct measure of how a patient feels or functions, and its interpretation depends on the marker's clinical context and on the reliability and completeness of the measurements. Those contextual details are not reported in the registry record.
The endpoint description identifies what was intended to be measured, but no numerical changes, variability estimates, or results by marker are reported in the registry record. It is therefore not possible to describe the direction, size, or precision of the observed changes from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a small, single-group study with 12 participants and a planned assessment of bone-resorption markers from baseline to 14 weeks. It does not report numerical primary-outcome results. The main statistical conclusion is therefore limited: the record describes the outcome and assessment time, but does not provide the observed changes needed to judge their direction, magnitude, or precision.
Even if within-participant changes were available, a single-group design would not establish what would have happened to the same participants over the same period without ACTIMMUNE. Changes could reflect treatment, the natural course of ADO2, measurement variation, other concurrent influences, or some combination. Without a control group, these explanations cannot be separated using a direct between-group comparison. This is a general limitation of interpreting before-and-after findings without a concurrent comparator.
The registry specifies that the primary outcome is expressed as percentage change, with a mean and full range. In general, a mean gives a measure of the average change, while a full range describes the smallest and largest values observed. A range can show the spread of observed values, but it does not by itself quantify the precision of the mean or establish how representative the participants are of a broader population. Confidence intervals or other uncertainty estimates for the primary outcome are not reported in the registry record.
The record lists 2 outcome measures and 0 analyses. That distinction matters: an outcome description does not provide an analysis result. Numerical findings, statistical tests, estimates of uncertainty, and details of any adjustments are not reported in the registry record. The results cannot be reconstructed from enrollment, outcome definitions, or adverse-event counts.
Safety information is reported separately from the primary marker outcome. The registry lists 0 affected among 12 at risk for serious adverse events and 10 affected among 12 at risk for other events. These counts do not supply the types, timing, severity, or attribution of the other events, and they should not be treated as evidence about the marker endpoint. The record lists 0 deaths.
Any sample-size estimates associated with the posted results are planning illustrations based on an observed effect, not evidence of observed power. They do not replace a reported outcome estimate or its uncertainty. The registry record does not include the numerical primary result needed to assess the observed effect in this study.
9. Statistical Methods Explained
In general, an open-label study is one in which treatment assignment is not masked from participants or investigators. Here, the registry explicitly lists masking as none. This can matter when outcomes involve judgments or decisions that may be influenced by knowledge of treatment. Laboratory measures may be less subjective than some outcomes, but open-label status does not remove other sources of bias, such as participant selection, follow-up patterns, or changes in measurement procedures. Details that would allow assessment of these issues are not reported in the registry record.
What does a single-group baseline comparison estimate?
The study is listed as single group, with no separate control arm. A baseline-to-follow-up comparison describes the change over time in the participants who were measured. In general, paired observations can account for the fact that a participant's follow-up value belongs to the same person as that participant's baseline value. However, the change still combines any treatment-related change with changes that could have occurred over time for other reasons. A concurrent control group can help distinguish those possibilities; this study has no such group in the registry description.
The registry identifies the outcome population as all subjects. That label gives a stated population for the primary outcome, but does not explain who had measurements available at each time point, how missing measurements were treated, or whether all enrolled participants were included in the final calculation. Those analysis details are not reported in the registry record.
What do the mean and full range convey?
The primary outcome is described as a mean percentage change, with full range as the dispersion summary. In general, the mean condenses a set of observations into an average. The full range records the lowest and highest observed values, so it can reveal whether the observed changes span a broad interval or include unusually extreme values. Neither summary alone shows the complete distribution. A range is also sensitive to extreme observations and does not quantify the precision of the estimated mean in the way a confidence interval is intended to do.
The record does not provide the numerical mean, full range, individual values, or confidence interval for the marker changes. It also does not report whether CTX and the NTX/creatinine ratio were analyzed separately, combined in any way, or subject to transformations. The outcome description names both markers, but the analysis details and results are not reported in the registry record.
Why does variability matter?
In general, variability describes how much measurements differ among participants or across repeated observations. A mean can look similar across two groups of observations even when their individual values are quite different. When data are highly variable, an average may give an incomplete picture of the range of participant experiences. The registry's choice to specify a full range offers one description of spread, but without the actual values or other distributional summaries, the amount and pattern of variability cannot be assessed.
Over-dispersion is a general issue for some statistical models: it occurs when observed variability is greater than a model assumes. If ignored, uncertainty estimates can be too small. The registry record does not identify a model for the marker outcomes, report a check for over-dispersion, or provide enough numerical results to assess whether this issue applies. It would therefore be inappropriate to claim that over-dispersion was present or that any particular correction was used.
What can planning estimates tell the reader?
In general, sample-size planning estimates describe the number of participants that would be needed under specified assumptions to detect a chosen effect with a stated error rate and power. The planning assumptions associated with the posted results specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a stated fraction of the observed effect. These are planning illustrations, not the design of this single-group trial: the trial did not have equal allocation between two arms. Any such estimates are not observed power, and they cannot establish that the study had a particular probability of detecting an effect. The numerical planning estimates are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures: a primary measure of change in bone-resorption markers from baseline to 14 weeks, and a secondary measure of change in bone-turnover markers after completion of 6-12 weeks of treatment. The primary outcome names CTX and the NTX/creatinine ratio. When a study examines multiple outcomes or markers, there can be more than one opportunity to observe a seemingly notable result by chance. In general, a statistical plan may address that issue by specifying which outcome is primary, how related tests will be handled, or whether adjustments will be made. A multiplicity plan is not reported in the registry record.
The record lists 0 analyses. It does not report test statistics, p-values, confidence intervals, or numerical outcome estimates. No conclusion about statistical significance or the consistency of findings across markers can be drawn from the outcome descriptions alone.
Missing-data handling is not reported in the registry record. The primary population is described as all subjects, but the record does not explain whether every participant contributed a baseline and follow-up measurement, how incomplete follow-up was handled, or whether any imputation or sensitivity analysis was used. These choices can affect a baseline-to-follow-up estimate, particularly when availability of measurements is related to participants' outcomes or experiences.
The registry also does not report a detailed analysis population, such as whether the primary analysis included all enrolled participants or only those with complete marker assessments. The description of all subjects should not be taken as evidence that all 12 had usable measurements for every endpoint. The analysis plan, multiplicity procedures, and missing-data methods are not reported in the registry record.
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 |
|---|---|---|---|
| Treatment | 0 | 12 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment | 0 of 12 |
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 |
|---|---|
| Treatment | 10 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment |
|---|---|---|
| Headache | Nervous system disorders | 10 of 12 |
| Fatigue | Nervous system disorders | 9 of 12 |
| nausea | Gastrointestinal disorders | 9 of 12 |
| flu like symptoms | Product Issues | 8 of 12 |
| myalgia | Musculoskeletal and connective tissue disorders | 7 of 12 |
| white blood cell decreased | Blood and lymphatic system disorders | 6 of 12 |
| arthralgia | Musculoskeletal and connective tissue disorders | 5 of 12 |
| diarrhea | Gastrointestinal disorders | 5 of 12 |
| neutrophil count decreased | Blood and lymphatic system disorders | 5 of 12 |
| vomiting | Gastrointestinal disorders | 5 of 12 |
The registry lists 12 participants at risk for serious adverse events, with 0 affected. It also lists 12 at risk for other adverse events, with 10 affected, and records 0 deaths. These are the safety counts in the treatment group.
The categories should be read as separate registry summaries. The record does not list the specific other events, their severity, timing, duration, or relationship to ACTIMMUNE. It also does not explain the criteria used to classify events as serious or other. The counts therefore describe how many participants are listed as affected in each category, but do not provide a full account of the safety experience.
A count of 0 affected for serious events is a report about this study group; it is not proof that serious events cannot occur. Likewise, the count for other events does not establish that treatment caused those events. Without a control group, detailed event descriptions, and further context, these figures cannot support a comparative safety estimate. The record does not report additional safety analyses.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed, open-label, single-group study enrolled 12 patients with ADO2 to evaluate ACTIMMUNE. It defines a primary outcome involving percentage change in CTX and the NTX/creatinine ratio from baseline to 14 weeks. It also reports safety counts for serious adverse events, other events, and deaths.
What the record does not establish is the observed change in either bone-resorption marker. Numerical primary-outcome results are not reported in the registry record. Without those values, it is not possible to characterize whether markers increased or decreased, how large any change was, how much participants varied, or how precisely the average change was estimated.
Even with a numerical before-and-after result, the single-group design would not show what the marker values would have been over the same period without ACTIMMUNE. General influences on change over time cannot be separated from treatment effects without an appropriate comparator. The record therefore cannot support a direct causal comparison or a conclusion about how the intervention compares with another option.
The endpoint concerns laboratory markers, not a reported measure of symptoms, function, or another patient-centered outcome. A change in a marker can inform a biological question, but it does not automatically establish a corresponding change in other outcomes. The registry record does not report such results or a link between marker changes and patient experience.
Finally, the safety counts describe participants listed as affected, but provide no event-level detail or comparative data. They should be interpreted as registry-reported counts, not as a complete assessment of risk or proof of causation. The study is informative about its design and intended measurements; the available record does not provide the outcome results needed for a fuller assessment.
13. Why This Trial Matters Statistically
This study is statistically notable for the distinction between a clearly defined measurement question and the evidence needed to answer it. The registry identifies a baseline-to-14-week change in bone-resorption markers, gives a summary type, and names the outcome population. Those details explain what the investigators intended to measure. Yet the absence of numerical outcome results means the statistical question cannot be answered from the registry record.
The single-group design also illustrates a central issue in clinical research. Measuring participants before and after treatment can describe change over time, but it does not provide the same information as a comparison with a concurrent control group. Without that comparison, observed changes cannot be attributed uniquely to treatment. This remains true even when the outcome is a laboratory marker and the study has a defined assessment time.
The registry records 12 enrolled participants. In general, the amount of information available from a study depends not only on enrollment, but also on the number with measured outcomes, the variability of those outcomes, and the analysis used. The record does not report the numerical primary results or enough analysis detail to assess those components. Planning illustrations based on an observed effect, if considered, are not observed power and are not a substitute for the trial's result.
The record also distinguishes outcome definitions from analysis reporting: it lists 2 outcome measures but 0 analyses. That makes clear why trial registration information and posted results need to be read separately. A specified endpoint does not reveal the observed estimate, its uncertainty, or how missing measurements were handled. This case highlights the value of complete reporting for interpreting both biological measurements and the limits of a study design.
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 most direct limitation is that numerical results for the primary endpoint are not reported in the registry record. Without those results, the direction, magnitude, variability, and precision of marker changes cannot be assessed. The registry lists 0 analyses, and no statistical test, confidence interval, or numerical outcome estimate is available.
The study has a single-group, open-label design and no separate control group. Within-group changes can describe what happened among those followed, but cannot distinguish treatment-related changes from other changes over time. The registry record does not report a comparator, masking, or a basis for a causal estimate.
The enrollment was 12, and the record does not provide participant characteristics beyond the ADO2 condition and recruitment description. It does not report how many participants contributed data to each marker assessment, whether anyone discontinued, or how missing measurements were handled. The analysis population is described as all subjects, but the record does not provide details that confirm the data available for each outcome.
The primary outcome definition names CTX and the NTX/creatinine ratio but does not report their results separately. Details about measurement procedures, laboratory methods, and any analysis decisions are not reported in the registry record. The record also does not report a multiplicity plan, a sample-size justification, interim analyses, or a detailed statistical analysis plan.
Safety reporting is limited to aggregate counts. Specific event terms, timing, severity, and attribution are not reported in the registry record. These limitations mean that the available record describes the study's design and intended assessments more fully than its results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Use of ACTIMMUNE in Patients With ADO2 — NCT02584608.
- Registry record last updated 2021-01-08; status last verified 2020-12.
- Results first posted 2021-01-08.
- 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
NCT02584608 is a completed Phase 2a, open-label, single-group study of ACTIMMUNE in patients with ADO2. The registry lists 12 enrolled participants and describes treatment as 50 µg/m2 subcutaneously three times per week for 8 weeks. The primary outcome is percentage change in CTX and the NTX/creatinine ratio from baseline to 14 weeks, summarized by a mean and full range.
Numerical primary-outcome results and statistical analyses are not reported in the registry record. Safety listings show 0 affected among 12 at risk for serious adverse events, 10 affected among 12 at risk for other events, and 0 deaths. The single-group design allows description of change over time but does not provide a concurrent treatment comparison.