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 and Efficacy of Romidepsin and the Therapeutic Vaccine Vacc-4x for Reduction of the Latent HIV-1 Reservoir (NCT02092116), a non-randomized phase 1, phase 2 study. The primary outcome is Part A: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02092116 |
| Phase | Phase 1, Phase 2 |
| Condition | HIV I Infection |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 26 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bionor Immuno AS |
| Results posted | Yes |
2. Clinical Question
Population
Adults with HIV-1 infection whose virus was suppressed on combination antiretroviral therapy were the intended population. The registry lists the condition as HIV I Infection and records enrollment of 26. The primary endpoint record does not further specify its analysis population.
Intervention
The study evaluated romidepsin, the therapeutic vaccine Vacc-4x, and rhuGM-CSF in a two-part study. Part A included a viral-reactivation phase using romidepsin infusions at 5 mg/m2 on days 0, 7, and 14. Part B included Vacc-4x with rhuGM-CSF at scheduled visits. The descriptions also refer to follow-up phases, but their text is incomplete in the registry record.
Comparator
No randomized control group is described. The registry classifies allocation as non-randomized, masking as none, and the model as single-group. Part A and Part B therefore should not be treated as randomized, like-for-like comparison groups. The registry record does not report a separate untreated or standard-treatment comparator for the primary safety endpoint.
Primary question
The primary endpoint asks how many participants experienced adverse events or serious adverse events during the stated three-week timeframe for Part A. It is a safety and tolerability measure, not a direct measure of whether the latent HIV-1 reservoir was reduced. The posted counts are reported by study part; they do not establish a causal contrast between interventions.
The broader study objective concerned changes in the latent HIV-1 reservoir and the use of immune stimulation alongside viral reactivation. Those aims explain the biological rationale described in the registry, but the primary endpoint recorded is adverse events and serious adverse events. The registry lists reservoir measures and HIV-1 transcription among secondary outcomes. Those measures address different questions from the primary safety endpoint, and their numerical results are not reported in the record details.
3. Trial Design
The registry describes an open Phase I/IIa study with non-randomized allocation, no masking, and a single-group model. It lists enrollment of 26 and marks the study completed. The study is divided into Part A and Part B in the posted safety results. These parts are not described as randomized arms, so their event counts should be read as separate descriptions rather than as a controlled comparison.
Part A is described as having a pre-treatment phase followed by a three-week viral-reactivation phase. The record states that this phase involved one cycle of romidepsin infusions at 5 mg/m2 on days 0, 7, and 14. A post-activation phase is also mentioned, but the arm description ends before its full details are available. Part B is described as having a pre-treatment phase followed by a twelve-week therapeutic immunization phase. Vacc-4x at 1.2 mg was administered with 0.06 mg rhuGM-CSF at Visits 2, 3, 4, 5, 6, and 7, followed by a stated two-week follow-up. The rest of the Part B description is incomplete in the registry record.
The primary safety outcome is framed over three weeks and counts participants with adverse events and serious adverse events. The posted safety data give separate at-risk counts and event counts for each study part. The registry also lists secondary outcomes concerning reservoir measures, adverse events in Part B, and HIV-1 transcription. It reports five outcome measures and no listed analyses. Further detail about how the parts relate to one another, how participants entered each part, and how the outcome data were analyzed is not reported in the registry record. The study’s open, non-randomized design limits interpretation of differences between the part-specific counts as evidence of an intervention effect.
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: 7 patients were screened and 6 patients were enrolled in Part A. 24 patients were screened and 20 patients were enrolled in Part B.
Overall Study
| Stage | Part A | Part B |
|---|---|---|
| STARTED | 6 | 20 |
| COMPLETED | 6 | 16 |
| NOT COMPLETED | 0 | 4 |
Reasons for not completing this period:
| Reason | Part A | Part B |
|---|---|---|
| Withdrawal by Subject | 0 | 3 |
| Adverse Event | 0 | 1 |
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 | Part A | Part B | Total |
|---|---|---|---|---|
| Participants analysed | 6 | 20 | 26 | |
| Age, Customized: >18 years | participants | 6 | 20 | 26 |
| Gender: Female | Participants | 1 | 3 | 4 |
| Gender: Male | Participants | 5 | 17 | 22 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 6 | 17 | 23 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
| Region of Enrollment: Denmark | participants | 6 | 20 | 26 |
| Time since HIV diagnosis | years | 13.3 (7.0 to 22.6) | 9.6 (2.6 to 28.7) | 9.85 (2.6 to 28.7) |
| Time since HIV infection | years | 13.5 (10.7 to 23.1) | 10.2 (2.7 to 31.7) | 12.2 (2.7 to 31.7) |
| Time since ART initiation | years | 10.05 (4.2 to 14.5) | 6.3 (2.4 to 18.1) | 6.9 (2.4 to 18.1) |
| Latest pre-ART viral load | copies/mL | 123300 (1977 to 2450000) | 67024 (3674 to 10000000) | 72597.5 (1977 to 10000000) |
| Nadir CD4+ T-cell count | 10^6 cells/L | 246.5 (40 to 340) | 280 (60 to 710) | 267.5 (40 to 710) |
| Mean CD4+ T-cell counts | 10^6 cells/L | 807.5 (570 to 1015) | 669.8 (465 to 1645) | 712.3 (465 to 1645) |
6. Primary Endpoint
The registry lists the primary outcome as Part A: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE), measured over 3 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with adverse events and serious adverse events in Part A during a stated three-week timeframe. The registry describes this endpoint as an evaluation of safety and tolerability. The posted results list six participants at risk for serious events and zero with a serious event; for other adverse events, six were at risk and six had an event. These are participant counts, not a measure of event severity for the non-serious category or a count of all individual events.
Safety endpoints are used to describe unwanted medical events observed during a study and to identify events classified as serious. Such counts help characterize what happened among participants under observation, but interpretation depends on the definitions, observation period, and completeness of event collection. The registry record does not provide the event definitions, criteria used to classify seriousness, or details about how events were collected and adjudicated.
The endpoint does not directly measure viral reservoir size, viral transcription, or the effect of treatment on HIV-1. Although those topics appear among the study aims and secondary outcomes, the primary result is a safety count. Without a randomized control group and fuller analysis details, the count alone cannot establish whether the interventions caused or prevented an event.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary safety data are descriptive. In Part A, the registry lists six participants at risk for serious adverse events and zero participants with a serious adverse event. For other adverse events, six participants were at risk and six had an event. These figures indicate that the posted record reports no serious event among the Part A participants included in that safety count, while every participant in the corresponding other-adverse-event count is recorded as having an event.
For Part B, the record lists 20 participants at risk for serious adverse events and one participant with a serious adverse event. It also lists 20 participants at risk for other adverse events and 20 with an event. These counts describe what was recorded for that part; they are not a randomized comparison with Part A. Differences in the counts could reflect differences in the participants observed, study procedures, exposure, follow-up, or event recording. The registry does not report enough detail to separate those possibilities.
The counts do not show how many events each participant experienced, when events began, how long they lasted, or whether they were judged related to a study intervention. The registry does not report confidence intervals or an inferential analysis for the primary endpoint. As a result, the precision of the underlying event frequencies cannot be assessed from the posted record beyond noting the denominators and counts recorded.
The registry lists Alcohol withdrawal syndrome as a serious-event term at 5.0%. The denominator and the precise relationship between that listed term and the part-specific serious-event counts are not stated in the record details. It should therefore be read as a reported term and percentage, not used to infer an unreported denominator or distribution across study parts.
The study’s stated objective also concerned the latent HIV-1 reservoir, but the primary safety counts do not answer whether reservoir measures changed. Although secondary outcomes list changes in HIV-1 DNA, replication-competent provirus, adverse events in Part B, and HIV-1 transcription, their numerical results are not reported in the registry record. The available safety figures support a limited description of recorded events, not conclusions about efficacy, comparative safety, or the biological objective.
9. Statistical Methods Explained
What kind of result is this?
The primary endpoint is a binary participant-level outcome: whether a participant was recorded as having an event in a category. The registry describes the measure as a number of participants, and the posted results give counts at risk and counts affected. These counts are straightforward descriptions of the observed safety data. They do not, by themselves, estimate a causal treatment effect.
General statistical explanation: For a binary outcome, a proportion is often used to describe how common an event was within the group under observation. Interpreting that proportion requires a clear denominator and a consistent definition of the outcome. In this record, at-risk and affected counts are listed for each part, but no confidence intervals are reported. A confidence interval is a range that conveys the uncertainty associated with an estimate under a specified statistical model. Its absence means the registry record does not quantify the precision of these event-frequency estimates.
Why does the design matter?
The study is described as open, non-randomized, and single-group. Randomization is generally used to make treatment groups comparable in expectation, reducing the likelihood that differences in participant characteristics explain differences in outcomes. That protection is not available for a comparison between Part A and Part B as. The registry does not describe those parts as randomized control groups, so their respective safety counts should not be interpreted as a treatment contrast. The record also does not report a masking procedure that might reduce influence on event assessment.
What can the counts establish?
The counts establish what the registry records for the specified safety categories and study parts. They do not indicate the number of separate events, because more than one event may occur in a participant and the posted measure counts participants. They also do not tell readers about timing, duration, severity among non-serious events, or attribution to study interventions. Those details are not reported in the registry record. The serious-event and other-event categories should be kept distinct rather than combined into a new total.
How should uncertainty be considered?
General statistical explanation: Estimates based on a limited number of observations can be imprecise, even when the observed count is clear. A count of zero does not prove that the underlying risk is zero; it describes the observations recorded in that group during the stated period. A confidence interval or a suitable model can express uncertainty, but neither is reported for this endpoint in the registry record. No new uncertainty interval can be inferred without choosing assumptions that are not documented.
For event counts, statistical methods may also need to distinguish the number of participants with at least one event from the total number of events. If participants can experience repeated events, modeling all event occurrences may require methods that account for within-participant dependence. The posted primary measure is the number of participants affected, not a recurrent-event total, and the registry does not report a model for repeated events.
What about over-dispersion?
General statistical explanation: Over-dispersion occurs when observed variability is greater than a statistical model assumes. It can matter for count models, where treating repeated events as independent or assuming a restrictive distribution can make uncertainty appear smaller than it is. The primary outcome is reported as a participant count with an event rather than a total count of repeated events. The registry does not report an over-dispersion assessment or a model for these results, so over-dispersion cannot be evaluated from the posted safety summary.
What analysis plan is documented?
The registry record lists no analyses for the outcomes. It does not report a statistical analysis plan, a prespecified method for comparing parts, adjustment variables, or an inferential test for the primary safety endpoint. It also does not report a sample-size justification. The recorded planning illustration assumptions refer to a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of an observed effect. Those are described as planning assumptions, not as the trial’s own design. No resulting planning sample-size figures appear in the record details, and such planning illustrations are not observed power.
What do the reservoir outcomes require?
Reservoir measures are listed as secondary outcomes, including total HIV-1 DNA, integrated HIV-1 DNA in unfractionated CD4+ T cells, and replication-competent provirus. These are different measurement types from the binary safety endpoint. The record does not provide their numerical results or analysis methods. In general, interpreting a change from baseline requires knowing the measurement scale, timing, analysis population, and method used to account for repeated measurements. Those details are not reported in the registry record and should not be filled in by assumption.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and no analyses. It identifies a primary safety outcome and several secondary outcomes, including reservoir measures, adverse events in Part B, and HIV-1 transcription. The registry record does not report which statistical tests, if any, were planned for these outcomes, how the outcomes were prioritized beyond the primary designation, or whether any adjustment for multiple comparisons was planned.
Multiplicity arises when several outcomes or statistical tests are considered. In general, the more opportunities there are to identify a nominally unusual result, the more important it is to interpret the analysis plan and any adjustment strategy. Because numerical results and analysis methods for the secondary outcomes are not reported in the registry record, their statistical evidence and the effect of any multiplicity approach cannot be assessed.
Information about missing outcome data, withdrawals, and analysis populations is also not reported in the registry record. The posted safety results state the at-risk counts for each part, but they do not explain whether every participant who entered a part contributed to each endpoint, why anyone might be excluded, or how incomplete follow-up was handled. Enrollment of 26 should not be assumed to be the denominator for every analysis. No intention-to-treat, per-protocol, or other analysis population is specified for the primary endpoint.
The record does not describe interim analyses, stopping rules, or methods for handling missing observations. These omissions limit assessment of how completely the reported counts represent the intended outcome populations. They do not establish that data were missing or that an adjustment was omitted in practice; they mean that those 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 |
|---|---|---|---|
| Part A | 0 | 6 | 0.0% |
| Part B | 1 | 20 | 5.0% |
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 |
|---|---|
| Part A | 6 of 6 |
| Part B | 20 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Part A | Part B |
|---|---|---|---|
| Alcohol withdrawal syndrome | Psychiatric disorders | 0 of 6 | 1 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part A | Part B |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 4 of 6 | 15 of 20 |
| Fatigue | General disorders | 3 of 6 | 15 of 20 |
| Injection site Pruritus | General disorders | 0 of 6 | 14 of 20 |
| Injection site erythema | General disorders | 0 of 6 | 8 of 20 |
| Constipation | Gastrointestinal disorders | 1 of 6 | 4 of 20 |
| Influenza like illness | General disorders | 1 of 6 | 4 of 20 |
| Headache | Nervous system disorders | 1 of 6 | 4 of 20 |
| Gastrointestinal sounds abnormal | General disorders | 3 of 6 | 1 of 20 |
| Pyrexia | General disorders | 1 of 6 | 3 of 20 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 6 | 2 of 20 |
Serious events with the highest arm-level rate: alcohol withdrawal syndrome (5.0%).
For serious adverse events, the posted results list six participants at risk and zero affected in Part A. In Part B, 20 participants were at risk and one was affected. These are part-specific participant counts over the recorded safety observation, not counts of all event episodes. The registry does not describe a randomized comparison between the parts, so these figures should not be used as evidence that one intervention or part was safer than the other.
For other adverse events, six participants were at risk and six were affected in Part A; in Part B, 20 were at risk and 20 were affected. The record does not provide event-level detail, severity grades for this category, onset times, duration, or an assessment of causal relationship. A participant-level count also does not show whether a person experienced one event or several.
The registry separately lists Alcohol withdrawal syndrome at 5.0% among the leading serious-event terms. The denominator and its relation to the part-specific counts are not reported in the registry record. It should not be used to reconstruct a group-specific rate. The absence of a serious event in the Part A count is a description of the recorded observations, not proof of no possible risk beyond those observations.
12. What the Result Does, and Does Not, Mean
The posted primary results describe adverse-event experience in two non-randomized study parts. They report no participant with a serious adverse event in the Part A safety count, and one participant with a serious adverse event in Part B. Other adverse events were recorded for all participants included in the respective at-risk counts. This is the scope of what the primary endpoint can establish from the posted figures.
The figures do not demonstrate that romidepsin, Vacc-4x, or rhuGM-CSF caused or prevented an event. Without randomized allocation and a suitable control comparison, the observed counts cannot distinguish intervention effects from differences in participants, exposure, follow-up, or event ascertainment. The registry does not report enough information to evaluate those sources of variation.
The results also do not answer whether the latent HIV-1 reservoir was reduced. The study objective and secondary outcomes refer to reservoir size and HIV-1 transcription, but their numerical results are not reported in the registry record. Safety counts are not a substitute for those biological outcomes, and the primary endpoint does not measure them.
Nor do the counts establish that adverse events were mild or severe beyond the serious-event classification. Event descriptions, severity grading for other events, relatedness assessments, and timing are not reported. The reported 5.0% for Alcohol withdrawal syndrome is not accompanied in the record details by a stated denominator, so it should not be translated into a group-specific frequency.
In general, a registry safety summary is useful for identifying what was recorded and the populations to which the counts refer. It is not a complete substitute for detailed outcome definitions, analysis methods, follow-up information, and a full account of missing data. The interpretation should remain descriptive and limited to the recorded counts.
13. Why This Trial Matters Statistically
This study raises a statistical distinction that matters in early-phase research: a biological rationale and a safety endpoint answer different questions. The study description links viral reactivation and therapeutic immunization to a proposed effort to address the latent HIV-1 reservoir. The primary endpoint, however, counts participants with adverse events and serious adverse events. A safety count cannot establish a change in reservoir measures, and reservoir measures would not by themselves establish the safety profile.
The design also makes clear why group labels should not be mistaken for a controlled comparison. Part A and Part B have separate descriptions and separate safety counts, but allocation is recorded as non-randomized, masking as none, and the model as single-group. Without a randomized comparator, differences between the part-specific counts have no straightforward causal interpretation. This is especially important when the treatment components and study periods differ across parts.
Statistically, the record illustrates the value of reporting denominators alongside event counts. Readers can see the at-risk and affected counts for each part, while also recognizing that the registry does not provide confidence intervals or a stated inferential analysis. The counts are informative descriptions, but they do not quantify uncertainty beyond the observed data.
Finally, the registry’s lack of reported analyses and detailed missing-data information constrains how far the results can be taken. These are not merely technical details: outcome definitions, analysis populations, event attribution, and follow-up determine what safety summaries mean. The record supports a focused description of recorded adverse events, while leaving broader efficacy and comparative questions unresolved.
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 registry record offers limited detail for interpreting the primary safety endpoint. It does not report the full event definitions, seriousness criteria, collection procedures, adjudication methods, or whether events were assessed as related to an intervention. It also does not report timing, duration, or severity grades for other adverse events. These omissions restrict the clinical and statistical interpretation of the counts.
The study is open and non-randomized, with no masking and a single-group model recorded. The separate Part A and Part B results therefore do not form a randomized comparison. The record does not explain in full how participants moved through the parts or whether the same participants contributed to each part’s safety count. That relationship is not reported in the registry record.
The arm descriptions are incomplete in the record details. Part A’s post-activation description and the remainder of Part B’s description are truncated. Consequently, the full intervention sequence and follow-up cannot be established from the available record details. The primary endpoint names a three-week timeframe, but additional detail about the safety observation window is not reported in the registry record.
The record lists enrollment of 26, while the safety results give their own at-risk counts by part. It does not explain the relationship between enrollment, entry into each part, and the population included in each endpoint count. Missing data, withdrawals, analysis populations, and any exclusions are not reported. The record also lists no analyses and provides no confidence intervals for the safety counts.
Finally, numerical results for the secondary reservoir and transcription outcomes are not reported in the registry record. The serious-event term Alcohol withdrawal syndrome is listed at 5.0%, but its denominator and its relationship to the part-specific counts are not stated. These limitations mean that the safety findings should remain descriptive and that biological or causal conclusions cannot be drawn from the primary endpoint alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of Romidepsin and the Therapeutic Vaccine Vacc-4x for Reduction of the Latent HIV-1 Reservoir — NCT02092116.
- Registry record last updated 2017-03-01; status last verified 2017-01.
- Results first posted 2017-03-01.
- 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
The registry describes a completed, open Phase I/IIa study of romidepsin and therapeutic HIV-1 immunization in adults with virologically suppressed HIV-1 infection. Allocation is recorded as non-randomized, masking as none, and the model as single-group. The study is divided into Part A and Part B, with intervention details that include romidepsin in Part A and Vacc-4x with rhuGM-CSF in Part B.
The primary endpoint is the number of participants with adverse events and serious adverse events in Part A over three weeks. The posted safety results list zero serious events among six at risk in Part A and one among 20 at risk in Part B. Other adverse events were recorded for six of six at risk in Part A and 20 of 20 at risk in Part B. The registry lists no analyses. It does not report confidence intervals, detailed event methods, missing-data handling, analysis populations, or numerical results for the secondary reservoir outcomes.