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 A Single Dose of Pembrolizumab in HIV-Infected People (NCT03367754), a randomized phase 1 study. The primary outcome is Number of Participants With Either Grade 2 or Higher Autoimmune Events and Grade 3 or Higher Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03367754 |
| Phase | Phase 1 |
| Condition | Human Immunodeficiency Virus |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes adults with HIV who were receiving antiretroviral treatment, had HIV levels below the detection limits of commercial assays, and had a low CD4+ T-cell count. The brief summary specifies a count below 350 cells/mm3; the arm descriptions specify a range of 100-350 cells/mm^3. The study included participants who received the intervention in its primary endpoint analysis.
Intervention
Participants assigned to the drug arm received a single intravenous dose of pembrolizumab 200 mg. The registry’s summary describes the infusion as lasting 30 minutes and notes observation afterward.
Comparator
The comparison arm received a single intravenous dose of placebo. The trial was randomized and parallel, with placebo as the control condition.
Primary question
The registered primary endpoint counted participants with either grade 2 or higher autoimmune events requiring corticosteroid therapy or grade 3 or higher adverse events judged possibly, probably, or definitely related to the intervention. The timeframe was up to 48 weeks from the start of intervention. The registry record does not report the endpoint counts or an arm-to-arm statistical analysis, so the comparative result for this question cannot be determined from the posted information.
3. Trial Design
NCT03367754 is a randomized, parallel-group phase 1 study of a single dose of pembrolizumab in people with HIV. Placebo was the comparator. The official title describes the study as double-blind, while the registry’s design listing specifies triple masking. These descriptions are both part of the registry record; further detail about who was masked is not reported in the registry record. The record does not state the allocation ratio or give additional details about how randomization was conducted.
The brief summary describes eligibility as age 18 years or older, HIV treated with antiretroviral drugs, HIV levels below the detection limits of commercial assays, and CD4+ T-cell count below 350 cells/mm3. The arm descriptions specify participants with CD4+ counts of 100-350 cells/mm^3. Screening was described as including medical history, physical examination, and heart, blood, and urine tests. The summary also describes leukapheresis and baseline assessments. These procedures provide context for the study but do not establish additional endpoint results.
The intervention was a single intravenous infusion: pembrolizumab 200 mg in the drug arm and placebo in the comparator arm. The registered enrollment was 11. The study began on 2018-08-06, had a primary completion date of 2021-12-17, and is listed as terminated. The reason for termination is not reported in the registry record.
The primary endpoint analysis population is described as all participants who received study intervention. That description does not establish how many participants in each arm were included in the endpoint analysis. The registry lists one outcome measure and no analyses. It does not report the endpoint results, a treatment-effect estimate, confidence interval, or p-value. Thus, randomization and the intended comparison are described, but the posted record does not provide the primary comparison needed to assess the endpoint between arms.
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: 11 participants were enrolled on the study. Three participants were screen failure and one participants withdrew prior to start of study.
Overall Study
| Stage | Drug: Pembrolizumab | Placebo |
|---|---|---|
| STARTED | 6 | 1 |
| COMPLETED | 6 | 1 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Analysis included all participants who received study intervention.
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 | Drug: Pembrolizumab | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 6 | 1 | 7 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 | 1 | 7 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Male | Participants | 5 | 1 | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 | 1 | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 4 | 0 | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Either Grade 2 or Higher Autoimmune Events and Grade 3 or Higher Adverse Events, measured over Up to 48 weeks from start of intervention.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a participant count for a composite safety outcome, assessed up to 48 weeks from the start of intervention. A participant qualifies if they experienced either an autoimmune event of grade 2 or higher that required corticosteroid therapy, or an adverse event of grade 3 or higher judged possibly, probably, or definitely related to the intervention. The registry says event severity was graded according to the Division of AIDS table for grading adult and pediatric adverse events.
Using a composite allows the endpoint to include more than one specified type of clinically important event. Here, the components are not simply any adverse event: they have severity, treatment, or relatedness conditions. A count of participants meeting the composite can therefore be different from a count of all adverse events or a count of serious adverse events. It also differs from counting repeated events, because the endpoint is explicitly framed as participants with an event.
Safety endpoints of this kind are used to monitor potential harms in a clinical study, particularly when the intervention is being evaluated in a phase 1 setting. The registry’s definitions clarify which events qualify, but the posted record does not give the primary endpoint count for either arm or specify a comparative estimate. The separate adverse-event counts cannot substitute for those missing endpoint results because their event categories are not described as applying the full composite criteria.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes that the study was randomized, placebo-controlled, and parallel, and that it evaluated a single dose of pembrolizumab. It also identifies a specific composite safety endpoint and a follow-up timeframe of up to 48 weeks. Those design details explain what the planned comparison concerned. They do not, by themselves, show the endpoint outcome.
The primary endpoint result is not reported in the registry record. No arm-specific count meeting the composite definition is posted, and no statistical comparison, effect estimate, confidence interval, or p-value is listed. The record therefore does not support a conclusion about whether the primary endpoint occurred more or less often in either arm, or how precise an estimated difference would be. The posted serious and other adverse-event figures describe separate categories and do not report whether events met the composite endpoint’s severity, treatment, and relatedness requirements.
The adverse-event entries report 1 serious event-afflicted participant among 6 at risk in the pembrolizumab group and 0 among 1 at risk in the placebo group. For other adverse events, the record reports 6 affected among 6 at risk in the pembrolizumab group and 1 among 1 at risk in the placebo group. Both groups have 0 deaths reported. These are descriptive counts from the adverse-event record, not a substitute for the unreported primary endpoint analysis. With small at-risk counts, each participant’s status has substantial influence on the displayed group count; the registry does not provide uncertainty intervals for these entries.
The registry also lists chest pain as a top serious-event term at 16.7%. That entry is a reported term and percentage, but the record does not supply enough context to infer a comparative risk or to connect it to the primary composite endpoint. It does not identify the event’s relation to the intervention in the information available for this interpretation.
Enrollment was 11, and the study is listed as terminated. The reason for termination and any impact on the availability or completeness of outcome reporting are not reported in the registry record. Accordingly, the safest statistical reading is descriptive: the study’s design and endpoint are documented, and selected adverse-event counts are posted, but the principal endpoint comparison is unavailable. No conclusion about treatment efficacy or the overall balance of benefits and harms follows from these records alone.
9. Statistical Methods Explained
Several statistical ideas help distinguish the trial’s intended question from the information actually posted. The registry identifies a randomized parallel-group design and a placebo comparator, but it does not provide a primary endpoint analysis. The terms below explain how such an analysis would generally be interpreted; they do not describe unreported methods as if they were used in this study.
What does a participant count measure?
The primary endpoint is a count of participants meeting the composite definition, rather than a count of every event. In general, participant-based outcomes ask whether each person experienced at least one qualifying event during the specified observation period. A person with repeated qualifying events would still be represented as a participant with an event if the endpoint is defined as a participant count. Event counts and participant counts answer different questions, so they should not be treated as interchangeable.
The composite also combines two routes to qualification: grade 2 or higher autoimmune events requiring corticosteroid therapy, and grade 3 or higher adverse events judged to have a specified possible relationship to intervention. In general, a composite can capture multiple clinically relevant event types in a single endpoint, but its interpretation depends on its components and the rules for qualifying. A total composite count alone would not reveal which component contributed unless component-level results were also reported. Those component counts are not reported in the registry record.
Why does the endpoint definition matter?
Severity grade, treatment requirement, and assessment of relatedness are part of the endpoint definition, not optional descriptive details. An adverse event may appear in an overall safety listing without meeting the endpoint’s specific grade or relatedness conditions. Conversely, a qualifying event may be counted in the primary endpoint according to its definition even if a separate summary presents safety information differently. The adverse-event entries posted for this study do not give the information needed to map each entry to the primary composite.
In general, event grading applies a structured framework to characterize severity. The registry says the study used the Division of AIDS grading table and gives descriptions of grade 2, grade 3, grade 4, and grade 5. The primary endpoint uses grade thresholds and, for one component, a corticosteroid-treatment condition. The record does not report adjudication procedures, who assigned grades, or how disagreements were handled.
How should arm comparisons be read?
For a binary endpoint, a common comparison presents the proportion of participants with an event in each arm and an estimate of the difference or relative effect, together with uncertainty. A confidence interval is a range of values compatible with the observed data under a specified statistical method; it communicates precision as well as the direction and scale of an estimate. A p-value, when reported, describes how incompatible the data are with a specified null model. Neither quantity alone establishes clinical importance, and neither can be interpreted without knowing the analysis and endpoint definition.
Those general interpretive tools cannot be applied to the primary endpoint in this record because its arm-specific results and inferential statistics are absent. The adverse-event counts do not have posted confidence intervals or p-values either. With sparse counts, standard approximations can be unreliable or uninformative, and uncertainty can be broad. The registry record does not state which inferential method, if any, was planned for the primary endpoint.
What do planning calculations mean?
The registry’s sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The contemplated effect to detect is expressed as a fraction of the observed effect. These assumptions do not establish the trial’s original design rationale, because the record does not report that rationale or a sample-size justification. Any planning illustration is not observed power: it does not measure the probability that the completed trial detected an effect, nor does it replace an uncertainty interval for the observed result.
In general, a planning sample size depends on the endpoint, the effect targeted, the expected variability or event rate, the allocation scheme, and the statistical test assumptions. A small study can yield imprecise estimates even when its design is randomized. Conversely, a planning calculation cannot establish whether an intervention has an effect. The numerical planning outputs are not reported in the registry record, and no new sample-size value can be inferred from the stated assumptions alone.
What is absent from the statistical record?
The registry lists no analyses. It does not report a prespecified statistical model, an analysis of the primary endpoint, an adjustment strategy, handling of repeated or competing events, or a method for missing observations. It also does not report a confidence interval or p-value for the primary result. These omissions mean readers cannot verify how the trial’s planned comparison was carried out or determine whether any model assumptions were assessed. They do not establish that such procedures were or were not conducted outside the information posted in the registry.
General statistical interpretation therefore begins with separating design, outcome definition, and analysis. The design identifies the groups intended for comparison; the endpoint defines what is counted; the analysis specifies how observed data are compared and uncertainty is quantified. For this study, the first two are described, while the primary results and analysis details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies one primary outcome measure, but its definition combines two qualifying event types. The record does not provide component-specific results, so it is not possible to determine whether one component drove any observed safety pattern. It also lists no analyses. The statistical plan, including any procedures for multiple endpoints, subgroup comparisons, repeated assessments, or interim analyses, is not reported in the registry record. No such procedures should be assumed.
Missing-data handling is also not described. The primary analysis population is stated to include all participants who received study intervention, but the record does not report arm-specific numbers analyzed, whether any endpoint observations were missing, how missing outcomes were handled, or whether participants who did not receive intervention were assessed. Without those details, the completeness and exact scope of the primary analysis cannot be evaluated.
In general, multiplicity matters when several outcomes or comparisons are tested because repeated testing can increase the chance of at least one apparently notable result under a null model. Missing-data methods matter because exclusions or assumptions about unobserved outcomes can affect estimates. These are general considerations, not evidence that multiplicity adjustments or particular missing-data methods were required or used in this trial. The registry record does not report enough information to assess either issue for the primary endpoint.
The posted endpoint count and comparison are absent, so there is no basis for evaluating the effect of missing data or multiplicity on a result. The registered population description should therefore be read as a statement of the intended analysis population, not as confirmation of complete outcome ascertainment or a particular statistical procedure.
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 |
|---|---|---|---|
| Drug: Pembrolizumab | 1 | 6 | 16.7% |
| Placebo | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Drug: Pembrolizumab | 0 of 6 |
| Placebo | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Drug: Pembrolizumab | 6 of 6 |
| Placebo | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Drug: Pembrolizumab | Placebo |
|---|---|---|---|
| Chest pain | General disorders | 1 of 6 | 0 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Drug: Pembrolizumab | Placebo |
|---|---|---|---|
| Blood cholesterol increased | Investigations | 5 of 6 | 0 of 1 |
| Blood triglycerides increased | Investigations | 5 of 6 | 0 of 1 |
| Blood glucose increased | Investigations | 3 of 6 | 1 of 1 |
| Low density lipoprotein increased | Investigations | 4 of 6 | 0 of 1 |
| Diarrhoea | Gastrointestinal disorders | 2 of 6 | 1 of 1 |
| Nausea | Gastrointestinal disorders | 2 of 6 | 1 of 1 |
| Sinusitis | Infections and infestations | 3 of 6 | 0 of 1 |
| Back pain | Musculoskeletal and connective tissue disorders | 2 of 6 | 1 of 1 |
| Headache | Nervous system disorders | 3 of 6 | 0 of 1 |
| Cough | Respiratory, thoracic and mediastinal disorders | 3 of 6 | 0 of 1 |
Serious events with the highest arm-level rate: chest pain (16.7%).
The adverse-event record lists serious events and other adverse events separately. For serious events, the pembrolizumab group has 1 affected participant among 6 at risk, and the placebo group has 0 among 1 at risk. For other adverse events, the pembrolizumab group has 6 affected among 6 at risk, and the placebo group has 1 among 1 at risk. The record reports 0 deaths in each group. Chest pain is listed among the top serious-event terms at 16.7%.
These are descriptive registry counts. They should not be confused with the primary composite endpoint, which requires specified severity, corticosteroid treatment, and/or a stated degree of relatedness to intervention. The posted adverse-event entries do not establish which events met those endpoint rules. Nor does the information identify the timing, recurrence, or participant-level overlap between serious and other event categories.
The group sizes at risk are small, and a count based on few participants is sensitive to each observed case. The registry does not provide uncertainty intervals or a comparative statistical analysis for these adverse-event entries. The listed counts therefore describe what the record reports; they do not by themselves establish a treatment-related difference or a causal interpretation.
12. What the Result Does, and Does Not, Mean
The record documents a randomized, placebo-controlled phase 1 study designed to assess a single pembrolizumab dose in adults with HIV and low CD4+ T-cell counts. Its primary safety endpoint is defined in detail and covers a period of up to 48 weeks from intervention start. The posted record also gives selected serious and other adverse-event counts. These registry entries help readers understand the study’s question and the scope of the safety information available.
The primary endpoint results are not reported in the registry record. There is no posted count of participants meeting its composite criteria in either arm and no comparative estimate or uncertainty interval. Consequently, the record cannot establish the direction, size, or precision of a difference in that endpoint. The adverse-event entries should not be used to fill this gap because they are not shown to apply the composite’s full criteria.
The registry also does not report an efficacy endpoint result. The study’s objective in the brief summary includes safety and immune-system effects, but the registry entries do not provide a result demonstrating a change in immune function or a treatment benefit. The existence of a study objective is not evidence that the objective was met. Likewise, the posted counts alone do not establish that an event was caused by the intervention.
In general, a randomized comparison can help estimate differences between assigned groups when outcomes and analyses are reported, but statistical precision depends on the amount and pattern of information available. Here, the registered enrollment is 11, and the posted information does not include the primary endpoint analysis needed for a comparative interpretation. The study’s termination status is recorded, but its reason is not reported.
The defensible conclusion is limited: the registry describes the design and safety endpoint and posts a small set of adverse-event counts, while leaving the primary comparison and analysis unavailable. Neither a claim of benefit nor a claim of no effect follows from the absence of a posted result.
13. Why This Trial Matters Statistically
This trial illustrates why a registry entry must be read at more than one level. Design details identify the intended comparison: random assignment to pembrolizumab or placebo in a parallel-group study. Endpoint details define what would count as a primary safety outcome. Results and analysis details are then needed to estimate the comparison and its uncertainty. The registry describes the design and endpoint, but does not report the primary endpoint analysis.
The distinction between a composite endpoint and general adverse-event summaries is statistically important. The primary outcome is not simply any event; qualification depends on event type, severity, treatment requirement, and relatedness criteria. Overall or separately categorized adverse-event counts may be useful safety descriptions, yet they cannot be assumed to reproduce a specifically defined composite. This prevents a common interpretive error: treating available counts as if they answered the registered primary question.
The record also shows why denominators and uncertainty matter in small studies. The serious-event counts are reported against small at-risk groups, and the registry provides no comparative interval or inferential analysis for them. Descriptive counts remain meaningful as descriptions, but they provide limited information about how precisely an underlying group difference is estimated. General statistical reasoning cautions against treating a small observed count as a stable estimate of risk.
Finally, planning calculations and observed results serve different purposes. The stated sample-size assumptions describe an illustrative planning framework; they are not observed power and do not substitute for the primary outcome estimate. A trial’s design rationale, analysis plan, and completed results each answer distinct questions. In this record, important statistical details—including the primary analysis and reason for termination—are not reported, making clear how registry completeness shapes what readers can responsibly infer.
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 main limitation for interpretation is that the registry does not report the primary endpoint result or a statistical comparison between arms. Without those results, the study’s central registered safety question cannot be answered from the posted record. The separate adverse-event counts do not provide the event-level criteria needed to reconstruct the composite outcome.
There is also limited detail about the analysis population. The record says the primary analysis included all participants who received study intervention, but does not give arm-specific endpoint denominators, missingness, exclusions, or follow-up completeness. The registry lists enrollment as 11, but does not show how many participants in each arm contributed to each adverse-event category or the primary endpoint.
The record does not report the statistical analysis plan, endpoint component results, uncertainty estimates, or handling of missing data. It also does not describe randomization procedures beyond randomized allocation, identify which roles were masked despite the difference between the title’s double-blind wording and the triple-masking design listing, or explain the reason for termination. Each of these omissions limits assessment of the conduct and interpretation of the comparison; none proves that a specific method was absent from study conduct outside the registry record.
Finally, the available adverse-event counts arise from small at-risk groups and are descriptive. They do not identify event timing, recurrence, overlap, or causal attribution. The chest-pain listing does not provide enough context to assess its relationship to intervention or the primary endpoint. These limitations make the registry useful for understanding the registered question and selected safety reporting, but insufficient for a complete statistical assessment of the trial’s primary result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Single Dose of Pembrolizumab in HIV-Infected People — NCT03367754.
- Registry record last updated 2025-01-17; status last verified 2024-11.
- Results first posted 2025-01-17.
- 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
NCT03367754 is a randomized, parallel-group phase 1 study comparing a single intravenous dose of pembrolizumab 200 mg with placebo in people with HIV. The registry lists triple masking; the official title describes the study as double-blind. Enrollment was 11, the study began on 2018-08-06, its primary completion date was 2021-12-17, and its status is terminated.
The primary endpoint counted participants with either grade 2 or higher autoimmune events requiring corticosteroid therapy or grade 3 or higher adverse events possibly, probably, or definitely related to intervention, up to 48 weeks from intervention start. The primary endpoint results and statistical analysis are not reported in the registry record. Separate adverse-event counts and 0 deaths in each group are posted, but they do not establish the primary composite result or a comparative treatment effect.