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 cAd3-Marburg Vaccine in Healthy Adults (NCT03475056), a non-randomized phase 1 study. The primary outcome is Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-Marburg Vaccine Administration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03475056 |
| Phase | Phase 1 |
| Condition | Marburg Virus Disease |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 40 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adults who received cAd3-Marburg vaccine. The registry record lists an enrollment of 40 participants and describes the primary endpoint population as all participants who received the vaccine.
Intervention
Intramuscular cAd3-Marburg vaccine, a chimpanzee adenovirus serotype 3 vector vaccine encoding wild type Marburgvirus glycoprotein. Group 1 received 1x10^10 PU and Group 2 received 1x10^11 PU.
Comparator
The study used sequential, non-randomized dose groups and had no masking. The registry record does not describe a separate control group. The two dose groups therefore should not be read as a like-for-like randomized comparison.
Primary question
How many participants reported local reactogenicity signs or symptoms during the 7 days after vaccine administration? Symptoms were recorded on diary cards and classified by worst severity. The registry record does not report the numerical results for this endpoint.
The primary question concerns short-term local symptoms after vaccination, not whether the vaccine prevents Marburg virus disease. The registry record also lists secondary immune-response outcomes: antibody responses to the vaccine vector and Marburg, and Marburg-specific T cell responses. These outcomes address immunogenicity, but their numerical results are not reported in the registry record. The trial is described as an open-label Phase I study focused on safety, tolerability, and immunogenicity in healthy adults. Its sequential dose-escalation design gives context for interpreting the two groups, but the registry record does not provide a randomized control comparison or numerical primary-endpoint results.
3. Trial Design
NCT03475056, titled “cAd3-Marburg Vaccine in Healthy Adults,” is recorded as a Phase I, open-label, non-randomized, sequential dose-escalation study. Its stated purpose was to examine the safety, tolerability, and immunogenicity of an investigational Marburg vaccine administered by intramuscular injection. The sponsor is the National Institute of Allergy and Infectious Diseases (NIAID). Enrollment was 40, and the study status is completed. The recorded start date is 2018-10-09 and the primary completion date is 2019-12-19.
The registry describes two vaccine groups. Group 1 received cAd3-Marburg vaccine at 1x10^10 PU, and Group 2 received 1x10^11 PU. Both descriptions specify intramuscular administration with a needle and syringe in a volume of 1 mL. The sequential model and non-randomized allocation mean the groups should not be treated as randomized arms. The registry record does not report the sequence or decision rules for dose escalation, nor does it describe a separate control group.
Open-label means the study was not masked according to the registry. The record identifies 12 outcome measures and no analysis records. It lists a primary safety outcome and secondary outcomes concerning antibodies to the cAd3 and Ad5 vectors, Marburg-specific antibodies, and Marburg-specific T cell responses. Numerical results for the primary endpoint and those immune outcomes are not reported in the registry record. The record also does not report details of the statistical analysis plan, sample-size justification, interim analyses, or handling of missing observations.
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 | Group 1: cAd3-Marburg Vaccine (1x10^10 PU) | Group 2: cAd3-Marburg Vaccine (1x10^11 PU) |
|---|---|---|
| STARTED | 20 | 20 |
| Received Product Administration | 20 | 20 |
| COMPLETED | 20 | 17 |
| NOT COMPLETED | 0 | 3 |
Reasons for not completing this period:
| Reason | Group 1: cAd3-Marburg Vaccine (1x10^10 PU) | Group 2: cAd3-Marburg Vaccine (1x10^11 PU) |
|---|---|---|
| Lost to Follow-up | 0 | 1 |
| Moved from Area | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: All participants who received the cAd3-Marburg vaccine.
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: Population includes all enrolled participants.
| Characteristic | Unit | Group 1: cAd3-Marburg Vaccine (1x10^10 PU) | Group 2: cAd3-Marburg Vaccine (1x10^11 PU) | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 20 | 40 | |
| Age, Customized: 18-20 years | Participants | 1 | 0 | 1 |
| Age, Customized: 21-30 years | Participants | 4 | 7 | 11 |
| Age, Customized: 31-40 years | Participants | 7 | 8 | 15 |
| Age, Customized: 41-50 years | Participants | 8 | 5 | 13 |
| Sex: Female, Male: Female | Participants | 12 | 13 | 25 |
| Sex: Female, Male: Male | Participants | 8 | 7 | 15 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 4 | 6 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 18 | 16 | 34 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 2 | 3 | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 10 | 4 | 14 |
| Race (NIH/OMB): White | Participants | 7 | 11 | 18 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Body Mass Index (BMI): 18.5-24.9 kg/m^2 | Participants | 6 | 8 | 14 |
| Body Mass Index (BMI): 25.0-29.9 kg/m^2 | Participants | 10 | 7 | 17 |
| Body Mass Index (BMI): 30.0-40.0 kg/m^2 | Participants | 4 | 5 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-Marburg Vaccine Administration, measured over 7 days after study product administration.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants reporting local reactogenicity signs and symptoms during the 7 days after cAd3-Marburg administration. Participants recorded solicited symptoms on a diary card for 7 days, then reviewed the card with clinic staff at a follow-up visit. A participant was counted once for each symptom, using the worst severity recorded if that symptom occurred more than once or at different severities. The “Any Local Symptom” measure counts participants who reported any local symptom at the worst severity.
The registry says symptom severity was graded as mild, moderate, or severe using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007). This endpoint is used to describe short-term local tolerability after administration. Counting participants rather than symptom episodes makes the measure a participant-level summary: repeated reports of the same symptom do not count as multiple participants.
The endpoint’s defined population is all participants who received cAd3-Marburg vaccine. However, numerical counts by symptom or severity are not reported in the registry record. Therefore, the endpoint definition explains what was intended to be measured, but does not establish how many participants experienced any particular local symptom or severity.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record supports a description of the study design and the way the primary safety endpoint was defined, but it does not report numerical results for that endpoint. The primary outcome is the number of participants reporting local reactogenicity signs and symptoms over 7 days after administration. Without the reported outcome counts by symptom and severity, the observed frequency and distribution of local symptoms cannot be characterized from this registry record.
The available adverse-event summary reports serious adverse events affecting 2 participants in Group 1 and 0 participants in Group 2. Other adverse events affected 11 participants in Group 1 and 16 participants in Group 2. The record lists 20 participants at risk for each category in each group, and reports 0 deaths in both groups. These are descriptive counts in a small, non-randomized dose-escalation study. They do not establish that the groups are comparable or that differences in counts are caused by dose. In particular, allocation was non-randomized and sequential, so the groups are not a like-for-like control comparison.
The serious-event terms listed in the record include Staphylococcal infection and Breast Cancer, each reported as 5.0%. The registry summary does not provide enough context to infer causality, timing, individual clinical circumstances, or which group these terms correspond to. A listed serious adverse event is not, by itself, evidence that the vaccine caused the event.
The registry identifies secondary outcomes for antibody and T cell responses, but does not report their numerical results. Consequently, the posted record does not permit an assessment of the size or precision of those immune responses. It also lists no analysis records. Inferential estimates, confidence intervals, and statistical tests are not reported in the registry record.
The enrollment of 40 describes the study as registered; it should not be interpreted as evidence that all enrolled participants received vaccine or contributed data to every outcome. The primary endpoint population is defined as vaccine recipients, but the registry record does not report outcome-specific denominators or missing-data handling. Overall, the available counts can be read as descriptive safety information, while efficacy, causal comparisons between doses, and detailed inferential conclusions are not established by the posted results.
9. Statistical Methods Explained
Several statistical ideas help distinguish what the registry describes from what can be concluded. The explanations below are general; they do not imply that a particular analysis was performed in this trial.
What does a participant count represent?
The primary endpoint is a count of participants with reported local symptoms, rather than a count of all symptom episodes. According to the endpoint definition, a participant is counted once for each symptom and the report uses that symptom’s worst severity when it occurred more than once. This approach summarizes how many people reported a symptom while avoiding treating repeated episodes in one person as separate people. The registry also defines “Any Local Symptom” as the number of participants reporting any local symptom at the worst severity.
A count is most interpretable alongside its denominator and the endpoint’s observation period. Here, the primary endpoint period is 7 days after administration, and the stated population is all participants who received vaccine. Numerical primary-endpoint counts and outcome-specific denominators are not reported in the registry record, so an incidence proportion or uncertainty interval cannot be described from this record.
Why does the design matter for group comparisons?
In a randomized comparison, allocation is intended to reduce systematic differences between groups, on average. This trial is recorded as non-randomized and sequential, so its dose groups are not randomized controls. Sequential dose escalation may be useful for describing experience across dose groups, but the registry does not report enough detail to reconstruct escalation decisions or other differences between groups. Any contrast between their observed counts would therefore be descriptive and potentially affected by group composition, timing, or other factors. The record itself cautions that the arms are not a like-for-like control comparison.
Open-label means masking was absent in the registry record. For participant-reported symptoms, awareness of treatment can potentially influence reporting or assessment in general. That is a design consideration, not evidence that reporting was biased in this study. The registry does not report procedures that would allow the presence or magnitude of such an effect to be assessed.
What would a confidence interval add?
In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified method. It helps readers judge whether an estimate is precise or compatible with a broad range of values. It does not guarantee that the range contains the true value, and it cannot correct for design limitations such as non-random allocation or missing data. The registry record does not report confidence intervals or other uncertainty estimates for the primary endpoint or secondary immune outcomes.
How should the serious-event counts be read?
The adverse-event summary gives counts of participants affected and counts at risk for serious and other adverse events in each group. These are descriptive summaries. A difference in observed counts is not automatically a treatment effect, especially in non-randomized groups. Serious-event counts also do not convey all clinical details, event timing, duration, or causal assessment. The registry record does not report those details in the summary available for interpretation.
What is over-dispersion?
In general, over-dispersion occurs when count data vary more than a statistical model assumes. A model that ignores over-dispersion can understate uncertainty and make estimates appear more precise than warranted. This concept is most relevant when count outcomes are analyzed with a model that makes assumptions about their variation. The primary endpoint in this record is specified as a participant count, but no model, dispersion estimate, or inferential analysis is reported. It would therefore be inappropriate to claim that over-dispersion was assessed or addressed.
What do planning illustrations mean?
In general, a sample-size planning illustration explores how many participants per arm might be needed under stated assumptions to detect an effect at a chosen significance level and power. Such an illustration is not an observed trial result and does not show the probability that this completed study found a real effect. The planning assumptions associated with the posted illustrations describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of the observed effect. Those are planning assumptions, not a reported justification for the trial’s enrollment. The registry record does not report the trial’s own sample-size justification, and no planning results should be mistaken for observed evidence.
More broadly, the registry record identifies 12 outcome measures but lists no analysis records. It does not report the statistical methods used for outcome estimates, adjustment for baseline factors, treatment of repeated measures, or uncertainty calculations. General statistical methods can explain how such analyses might work, but they cannot fill in undocumented trial methods or results.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 12 outcome measures, including a primary local reactogenicity endpoint and secondary outcomes covering vector antibodies, Marburg-specific antibody responses, and Marburg-specific T cell responses. When multiple outcomes are examined, there is a general statistical issue called multiplicity: the chance of at least one apparently notable result can increase as more tests are considered. Researchers may address this in different ways, depending on the study’s aims and analysis plan. The registry record does not report whether multiplicity adjustments or a hierarchy among outcomes were planned or used.
The record lists no analysis records, and numerical results for the primary and secondary outcomes are not reported. It therefore does not provide a basis for assessing which outcome analyses were conducted, how estimates were selected, or whether any multiplicity strategy was applied.
Missing-data methods also matter because the available observations may differ across outcomes. The primary endpoint is defined for all participants who received vaccine, but outcome-specific denominators, missing diary information, and rules for handling incomplete reports are not reported in the registry record. The registry also does not describe how missing antibody or T cell measurements were handled.
The record defines the primary endpoint population but does not provide a fuller analysis-population description, such as which participants contributed to each analysis. No assumptions about missingness or participant exclusions can be inferred. These gaps limit the ability to evaluate completeness and reproducibility of the reported outcomes.
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 |
|---|---|---|---|
| Group 1: cAd3-Marburg Vaccine (1x10^10 PU) | 2 | 20 | 10.0% |
| Group 2: cAd3-Marburg Vaccine (1x10^11 PU) | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1: cAd3-Marburg Vaccine (1x10^10 PU) | 0 of 20 |
| Group 2: cAd3-Marburg Vaccine (1x10^11 PU) | 0 of 20 |
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 |
|---|---|
| Group 1: cAd3-Marburg Vaccine (1x10^10 PU) | 11 of 20 |
| Group 2: cAd3-Marburg Vaccine (1x10^11 PU) | 16 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1: cAd3-Marburg Vaccine (1x10^10 PU) | Group 2: cAd3-Marburg Vaccine (1x10^11 PU) |
|---|---|---|---|
| Staphylococcal infection | Infections and infestations | 1 of 20 | 0 of 20 |
| Breast Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 20 | 0 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1: cAd3-Marburg Vaccine (1x10^10 PU) | Group 2: cAd3-Marburg Vaccine (1x10^11 PU) |
|---|---|---|---|
| Administration site pain | General disorders | 11 of 20 | 16 of 20 |
| Malaise | General disorders | 5 of 20 | 13 of 20 |
| Headache | Nervous system disorders | 6 of 20 | 11 of 20 |
| Myalgia | Musculoskeletal and connective tissue disorders | 5 of 20 | 9 of 20 |
| Chills | General disorders | 3 of 20 | 6 of 20 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 2 of 20 | 7 of 20 |
| Anaemia | Blood and lymphatic system disorders | 2 of 20 | 4 of 20 |
| Upper Respiratory Tract Infection | Infections and infestations | 1 of 20 | 4 of 20 |
| Nausea | Gastrointestinal disorders | 2 of 20 | 2 of 20 |
| Pyrexia | General disorders | 0 of 20 | 3 of 20 |
Serious events with the highest arm-level rate: staphylococcal infection (5.0%), breast cancer (5.0%).
The registry’s adverse-event summary reports serious adverse events affecting 2 participants in Group 1 and 0 participants in Group 2. The number at risk is 20 in each group. For other adverse events, 11 participants in Group 1 and 16 participants in Group 2 were affected, with 20 at risk in each group. Deaths are reported as 0 in both groups.
These are descriptive participant counts. Because the trial was non-randomized and sequential, the groups do not form a randomized control comparison; the counts should not be interpreted as causal evidence that one dose produced more or fewer events. The record does not report a causal assessment for the listed events, nor does the summary establish timing, duration, or individual circumstances.
Staphylococcal infection and Breast Cancer are listed among the top serious-event terms, each at 5.0%. The registry summary does not identify the group associated with each term or provide enough detail to interpret a relationship to vaccination. Seriousness describes an event category; it does not by itself establish that the vaccine caused the event. The 0 deaths reported in each group is a death count, not a complete measure of safety.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a completed, open-label Phase I dose-escalation study of cAd3-Marburg vaccine in healthy adults, with two non-randomized dose groups. It also specifies a primary safety endpoint based on participant-reported local symptoms during the 7 days after administration. The adverse-event summary gives descriptive counts by group, including serious events, other events, and deaths.
These registry entries do not establish whether the vaccine prevents Marburg virus disease. The stated study objectives were safety, tolerability, and immunogenicity, and the registry record does not report numerical results for the listed immune outcomes. Nor does the record provide numerical results for the primary local reactogenicity endpoint. The available adverse-event counts alone cannot establish a causal relationship between vaccination and any event.
The two dose groups should not be interpreted as if participants had been randomly assigned to comparable treatments. The non-randomized, sequential design leaves open the possibility that groups differed in ways that could affect observed counts. No inferential comparisons or uncertainty estimates are reported in the registry record. As a result, the size and precision of any difference between groups cannot be evaluated from these data.
For the same reasons, the counts should not be generalized beyond the study population without further evidence. The record concerns healthy adults and does not provide outcome-specific denominators, details of missing data, or the full analysis populations. A completed study status indicates that the study is recorded as completed; it does not supply missing outcome results or substitute for a detailed analysis.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why study design and outcome reporting shape interpretation. It was a Phase I, open-label, sequential dose-escalation study, not a randomized comparison. The two dose groups offer a setting for describing safety experience across doses, but non-random allocation limits the strength of causal comparisons. The registry explicitly cautions that the arms are not a like-for-like control comparison.
The primary endpoint also illustrates the importance of precise outcome definitions. It counts participants reporting local symptoms during a defined 7-day period and uses the worst severity for a symptom reported more than once. That definition clarifies what the measure is intended to represent, while the absence of numerical endpoint results prevents readers from estimating how common symptoms were in the study.
The registry lists multiple immune-response outcomes as well as the primary safety outcome. This makes transparent analysis methods and reporting of uncertainty especially relevant in general: readers need to understand which comparisons were planned, how multiple outcomes were handled, and how complete the data were. Those details, along with numerical immune-response results, are not reported in the registry record.
The available adverse-event counts show why descriptive safety summaries must be read with design context. Counts by group can describe what was recorded, but they do not isolate the effect of dose in a non-randomized study. The distinction between a recorded event and an event caused by vaccination is also essential. The registry provides a study framework and some adverse-event counts, but does not provide the endpoint results or analysis details needed for stronger statistical conclusions.
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 for interpreting outcomes is that the registry record does not report numerical results for the primary endpoint. Although the symptom collection period, counting rule, severity grading, and intended population are described, the symptom counts by severity are not available in the record. Numerical results for the listed immune-response outcomes are also not reported.
The design was open-label, sequential, and non-randomized. Consequently, the two dose groups are not randomized controls, and observed differences cannot be interpreted as dose effects without additional assumptions and analysis. The registry record does not report the detailed escalation process or other design features that could clarify how participants entered each group.
The adverse-event summary provides affected-participant counts and numbers at risk, but does not report event-level context such as timing, duration, or causal assessment. The serious-event terms listed are not linked to a group in the summary, so group-specific interpretation of those terms is not possible from the registry record.
The record lists 12 outcome measures but no analysis records. It does not report a statistical analysis plan, inferential estimates, confidence intervals, multiplicity handling, missing-data methods, or outcome-specific analysis populations. It also does not report the trial’s sample-size justification. These omissions constrain assessment of precision, completeness, and reproducibility. Enrollment is listed as 40, but outcome-specific denominators are not reported; the enrollment figure alone does not show how many participants contributed data to each endpoint.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: cAd3-Marburg Vaccine in Healthy Adults — NCT03475056.
- Registry record last updated 2022-08-11; status last verified 2022-08.
- Results first posted 2021-01-14.
- 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
NCT03475056 is a completed Phase I, open-label, non-randomized, sequential dose-escalation study of cAd3-Marburg vaccine in healthy adults. The registry lists an enrollment of 40, a start date of 2018-10-09, and a primary completion date of 2019-12-19. The two groups received 1x10^10 PU and 1x10^11 PU, respectively, by intramuscular injection.
The primary endpoint counts participants reporting local reactogenicity during the 7 days after administration. The registry lists 12 outcome measures and no analysis records. It reports descriptive adverse-event counts, including 2 serious-event-affected participants in Group 1 and 0 in Group 2, other-event counts of 11 and 16, and 0 deaths in each group. Numerical primary and immune-response results, detailed analysis methods, and missing-data procedures are not reported in the registry record.