A Study Of The Safety And Effects Of One Or More Doses Of HSP-130 Injected Under The Skin In Women With Breast Cancer That Has Not Spread To Distant Sites In The Body.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Of The Safety And Effects Of One Or More Doses Of HSP-130 Injected Under The Skin In Women With Breast Cancer That Has Not Spread To Distant Sites In The Body. (NCT02650193), a registered phase 2 study. The primary outcome is Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0.

2. Clinical Question

In statistical terms, the endpoint summarizes the measured neutrophil-count response over the stated Cycle 0 observation period. The study also listed measures of maximum neutrophil and CD34+ effects, timing of those effects, and drug exposure. These measures address different features of response and exposure; they do not turn the dose groups into a controlled comparison. The record describes 25 participants enrolled, but does not report a numerical primary-endpoint estimate or a confidence interval. Thus, the clinical question can be described from the design, but the size and uncertainty of the primary response cannot be assessed from the registry results.

3. Trial Design

The registry classifies this as a phase 2, parallel study with no masking. Its official title describes a phase 1-2 ascending-dose study of HSP-130, assessing pharmacodynamics, pharmacokinetics and safety after single-dose and multiple-dose subcutaneous administration. The study is recorded as completed, with 25 participants enrolled. The record lists non-metastatic breast cancer as the condition and Pfizer as the sponsor.

The listed treatment groups were organized by cycle and dose. Cycle 0 included a single 3 mg subcutaneous injection and a single 6 mg subcutaneous injection, both described as being given in the deltoid region. For Cycles 1-4, the registry describes a 6 mg injection at least 24 hours after chemotherapy administration. The arm description in the registry record ends before fully specifying the chemotherapy context, so further details of that regimen are not reported in the registry record.

The study summary says participants could be studied before breast surgery or while receiving chemotherapy. Its stated aims included examining white blood cell counts, drug levels and safety, and identifying a dose to take forward for future clinical trials. The primary endpoint concerned the Cycle 0 area under the effect curve for absolute neutrophil count. Other listed outcomes included measures of neutrophil and CD34+ response and serum drug exposure.

This was not a randomized comparison according to the registry information: allocation is not stated, and the listed groups are not a like-for-like control comparison. The record does not report the allocation method, a protocol-level statistical analysis plan, or a sample-size justification. The study dates recorded are a start in 2015-12 and primary completion in 2017-10.

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

Analysis population for the primary outcome, as defined in the registry: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycles 1-4: HSP-130 6mg arm.

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) included all participants who received at least 1 dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0, measured over Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose.

The primary endpoint was the area under the effect curve for absolute neutrophil count (ANC) during Cycle 0. ANC measures the number of neutrophil granulocytes in the blood. The registry gives the endpoint unit as hour*10^9 Neutrophils per Liter and describes the summary measure as a mean with standard deviation.

Measurements were scheduled at predose (0 hour), then 48, 96, 144, 192, 240 and 312 hours post-dose. An area-under-the-curve measure uses observations across time to represent the overall measured response over the specified interval, rather than focusing only on a single measurement. General explanation: this can be useful when a response changes over time, because both its magnitude and duration contribute to the summary. The exact calculation method used for this endpoint is not reported in the registry record.

The primary measure was specified for Cycle 0. The registry states that it was not planned to be analyzed for the Cycles 1-4 HSP-130 6mg arm. The full analysis set included participants who received at least one dose of study medication. The record does not give the primary endpoint’s numerical mean, standard deviation, or confidence interval. Consequently, the endpoint definition and measurement schedule are available, but the observed response and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized by a mean and standard deviation. It also identifies the measurement times, the analysis population, and the Cycle 0 period of interest. It does not report the numerical endpoint estimate or a confidence interval. The statistical concepts below are general explanations of how such methods are commonly interpreted; they are not claims about additional analyses performed in this study.

What does an area-under-the-curve endpoint represent?

General explanation: when a biological measure is recorded repeatedly over time, an area-under-the-curve summary combines those measurements into a single representation of the response across the defined period. It reflects the pattern across the observation window rather than just the reading at one selected time. The interpretation depends on the endpoint’s units, the time points, and the calculation rule. Here, the registry lists ANC observations from predose through 312 hours post-dose and gives the endpoint unit as hour*10^9 Neutrophils per Liter. The specific interpolation or calculation procedure is not reported in the registry record.

An area-under-the-curve value is not interchangeable with a maximum value or a time-to-maximum measure. The registry separately lists maximum-effect and timing outcomes for ANC and CD34+. Those measures address peak magnitude and when it occurs, while an area-under-the-curve measure represents response over time. These endpoints may provide complementary descriptions, but they answer different statistical questions.

What do a mean and standard deviation tell the reader?

General explanation: a mean describes the center of a set of observations, while a standard deviation describes their spread around that mean. A mean alone does not show how variable individual observations were. A standard deviation is not a confidence interval: it describes variation among observations, whereas a confidence interval expresses uncertainty about an estimated quantity under a statistical model. The registry specifies mean and standard deviation for the primary measure but does not report the corresponding numerical values or a confidence interval.

In a small study, descriptive estimates can be sensitive to the observations included. General explanation: a confidence interval can help communicate the precision of an estimate, but its interpretation relies on the method and assumptions used to construct it. Since an interval is not reported for the primary outcome in the registry record, its precision cannot be assessed from the listed endpoint definition alone.

Why does the comparison structure matter?

The trial is described as parallel and unmasked. The registry does not state an allocation method and cautions that the arms are not a like-for-like control comparison. General explanation: a controlled comparison is most informative when groups are made comparable by design, so differences in outcomes can be interpreted in relation to the assigned treatment. When that structure is absent or unclear, observed differences may reflect characteristics of the groups, treatment context, or other factors as well as dose. A comparison among these listed groups should therefore be treated as descriptive, not as a randomized estimate of a dose effect.

No placebo or untreated comparator is listed. The described groups received HSP-130 at different doses or in different cycle contexts. The registry’s design description does not support attributing differences between groups solely to dose or schedule.

How should the planning illustrations be read?

The registry describes planning illustrations computed from the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total event count; for other outcomes, it uses participants per arm. General explanation: such calculations ask what sample size might be needed under specified assumptions to detect a selected effect. They are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions.

The registry record does not report the trial’s own sample-size justification. It also does not provide numerical planning outputs in the registry record for this analysis. No sample-size estimate can therefore be inferred from the stated assumptions alone.

What does over-dispersion mean in general?

General explanation: for count data, over-dispersion means that variability is greater than a chosen statistical model expects. If ignored, standard errors and intervals from that model may be misleading. The primary outcome in this study is a continuous area-under-the-curve measure, and the registry does not state that an over-dispersed count model was used. The concept should not be mistaken for a reported feature of this analysis.

More broadly, the choice of statistical model depends on the outcome, design, and data structure. The registry information does not describe a model for the primary outcome, adjustment variables, missing-data procedure, or inferential testing strategy. Those details are not reported in the registry record, so the endpoint definition should not be taken as a complete account of the analysis method.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Cycle 0: HSP-130 3mg", "Cycles 0: HSP-130 6mg")
n   <- c(6, 6)
m   <- c(3900.482, 5880.985)
sp  <- c(683.687, 1287.2887)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Cycle 0: HSP-130 3mg  6  3900.482  683.687  3182.996  4617.968
CARM  Cycles 0: HSP-130 6mg  6  5880.985  1287.289  4530.058  7231.912

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 46 outcome measures, including the primary ANC area-under-the-curve measure and secondary measures of ANC, CD34+ response and serum drug exposure. Considering many outcomes can raise a multiplicity question: if several statistical tests are conducted, the chance of finding at least one apparently unusual result can increase. General explanation: investigators may address this through a prespecified hierarchy, adjusted significance thresholds, or a focus on estimation rather than repeated testing. The registry record does not report whether any multiplicity procedure was planned or used.

No analyses are listed in the registry record. That means numerical analysis results and any analysis-specific methods cannot be assessed from this record. It does not establish what analyses may have been conducted outside the registry.

The primary analysis population is described as the full analysis set, including participants who received at least one dose of study medication. The endpoint was not planned to be analyzed for the Cycles 1-4 HSP-130 6mg arm. The record does not report how missing ANC measurements were handled, whether participants with incomplete measurement schedules were included in the endpoint calculation, or how missing outcome data were treated in other analyses.

Allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. The sample-size justification and detailed statistical analysis plan are also not reported in the registry record. These omissions limit evaluation of prespecification, missing-data assumptions, multiplicity control, and the intended interpretation of between-group summaries.

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: febrile neutropenia (15.4%).

The registry reports serious adverse event counts by listed group. For Cycle 0: HSP-130 3mg, 0 of 6 participants at risk were reported as affected by a serious adverse event. For Cycle 0: HSP-130 6mg, the corresponding figures were 0 of 6. For Cycle 1-4: HSP-130 6mg, 2 of 13 were reported as affected. No deaths were reported in any of these groups. Febrile Neutropenia appears among the top serious event terms, with a reported rate of 15.4%.

These are descriptive safety figures from groups with limited enrollment, not a controlled comparison. The registry record does not give enough information to determine whether the event-term rate represents a participant-level risk over a common observation period or to compare it directly across regimens. The listed figures also do not establish that an event was caused by HSP-130.

The record separately lists other adverse events affecting 6 of 6 participants in each Cycle 0 group and 13 of 13 in the Cycles 1-4 group. These counts should not be confused with serious adverse events. The registry record does not provide further event-level detail in the registry record for this analysis. Absence of reported deaths in these groups is a description of the registry entries, not a broader safety conclusion.

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

This study addresses the characterization of HSP-130 pharmacodynamics, pharmacokinetics and safety in women with non-metastatic breast cancer. Its central endpoint was a Cycle 0 summary of ANC response over time, with additional listed measures for neutrophil and CD34+ responses and serum drug exposure. The record also states that selecting a dose for future clinical trials was an aim.

The registry information does not report the numerical primary endpoint result. It therefore does not show the size of the ANC area-under-the-curve estimate, its variability, or the precision with which it was estimated. It also does not report numerical results for the additional listed outcomes in the registry record for this analysis. The endpoint definitions and schedule explain what was to be assessed, but do not substitute for the observed results.

The safety entries describe reported events within the listed groups. They do not provide a randomized comparison with an untreated or placebo group, and the registry cautions that the arms are not like-for-like controls. As a result, differences between groups cannot be interpreted as causal dose effects from these registry entries alone. The serious event counts and event term are useful descriptive context, but they do not establish comparative safety or causation.

General explanation: an early dose-characterization study can inform the questions considered in later research, but a dose-selection aim is not itself evidence that a particular dose is effective or safe. This record does not report the dose-selection decision, the reasoning behind it, or a comparative clinical outcome. It also does not report the protocol’s sample-size justification, detailed statistical analysis plan, multiplicity approach, or missing-data methods. The appropriate interpretation is therefore limited to the design and descriptive information recorded, with efficacy magnitude and statistical uncertainty unresolved in the registry record.

14. Why This Trial Matters Statistically

Statistically, the study is notable for its emphasis on repeated biological measurements after single and multiple subcutaneous doses. The primary ANC endpoint uses an area-under-the-curve summary across scheduled measurements, while the other listed outcomes include peak-response, timing, CD34+ and drug-exposure measures. This illustrates how a dose-characterization study may describe several dimensions of response rather than rely on a single measurement at one time point.

The trial also illustrates why design details matter when interpreting groups. Although the record describes a parallel study and distinct dose or cycle regimens, allocation is not stated and the arms are explicitly not a like-for-like control comparison. That limits the strength of any causal interpretation of differences between regimens. A descriptive pattern can motivate questions for later research, but it cannot by itself isolate a treatment effect.

The gap between a defined endpoint and a reported endpoint estimate is also important. The registry specifies the measure, units, time points and analysis population, but the numerical primary result is not reported in the available record. Without an estimate and precision measure, readers cannot assess the observed magnitude or its uncertainty. The listed 46 outcomes further underscore the value of a transparent analysis plan, including how multiple outcomes and missing observations are handled; those methods are not reported in the registry record.

Finally, the safety information demonstrates the distinction between event counts and comparative safety evidence. Serious and other adverse events are reported by group, but the groups do not provide a randomized control comparison. The figures are informative as descriptive records while remaining insufficient to establish comparative risks. These design and reporting features make the trial useful for understanding what was measured and what remains unanswered.

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 direct limitation for statistical interpretation is that the numerical primary outcome result is not reported in the registry record. The mean and standard deviation are specified as the intended summary, but the record available for this analysis does not give those values or a confidence interval. Thus, neither the magnitude nor precision of the primary ANC response can be evaluated.

The registry lists multiple treatment regimens, but allocation is not stated and it cautions that the arms are not a like-for-like control comparison. This prevents a strong causal interpretation of differences across groups. The Cycle 1-4 description also concerns participants receiving chemotherapy, whereas the Cycle 0 regimens are described as single-dose groups; the record does not establish that these contexts are directly comparable.

The primary outcome was not planned for the Cycles 1-4 HSP-130 6mg arm. The record does not report how missing measurements were handled or how incomplete observation schedules affected endpoint calculation. It does not describe the statistical model, multiplicity procedure, or detailed analysis plan. The study’s sample-size justification is not reported in the registry record; planning illustrations based on an observed effect should not be mistaken for the original design rationale.

Safety counts are descriptive and arise from the listed groups. The record does not provide a controlled comparison, and the event counts alone cannot establish causation. Further detail on exposure duration and event-level context is not reported in the registry record in the registry record for this analysis. These limitations constrain what can be concluded from the registry information, especially about comparative effects, precision and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Of The Safety And Effects Of One Or More Doses Of HSP-130 Injected Under The Skin In Women With Breast Cancer That Has Not Spread To Distant Sites In The Body. — NCT02650193.
• Registry record last updated 2018-10-23; status last verified 2018-09.
• Results first posted 2018-10-23.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed phase 2, parallel, unmasked study of HSP-130 enrolled 25 participants with non-metastatic breast cancer. The registry describes single-dose Cycle 0 regimens of 3 mg and 6 mg and a 6 mg regimen across Cycles 1-4. Its primary outcome was the Cycle 0 area under the effect curve for ANC, summarized as a mean and standard deviation in the full analysis set.

The record lists 46 outcome measures but no analyses. A numerical primary-endpoint result is not reported in the registry record. Safety entries include serious adverse event counts by group, no reported deaths, and Febrile Neutropenia as a top serious event term with a rate of 15.4%. Allocation is not stated, and the arms are not a like-for-like control comparison. The detailed statistical plan, sample-size justification, multiplicity handling and missing-data methods are not reported in the registry record.