A Study of the Safety, Engraftment, and Action of NB01 in Adults With Moderate Acne: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Safety, Engraftment, and Action of NB01 in Adults With Moderate Acne (NCT03450369), a na phase 1 study. The primary outcome is Number of Participants With Successful Engraftment of Probiotic Following a Single Application..

2. Clinical Question

The study was intended to assess safety, tolerability, short-term engraftment and clinical impact after a single application in adults with moderate acne. Its stated rationale concerns replacing disease-associated bacterial strains with health-associated strains, rather than eliminating all skin bacteria. That rationale is the investigators’ hypothesis, not an outcome demonstrated by the registry record.

The central statistical question is descriptive: among participants receiving NB01, how many met the specified assay-based threshold for engraftment? A control group would be needed to make a direct comparison with no application or another treatment. Because no such control is described, the study cannot establish a comparative effect against those alternatives. The record also does not report a primary endpoint count, so the observed frequency of successful engraftment cannot be evaluated from the posted results.

3. Trial Design

This is a Phase 1 study, described in the official title as a Phase 1B dose-escalating study. It is listed as completed, with a recorded enrollment of 10. The recorded start date is 2018-01-24 and the primary completion date is 2018-06-18. The study concerns adults with moderate acne and evaluates a single application of NB01.

NB01 is described as a live strain of P. acnes, presented frozen on a pad in a single-use pouch for topical application. The registry lists Low Dose and High Dose groups. Its description says the study was open label and involved dose escalation, and mentions approximately 5 subjects assigned to the lower-bound dose before escalation. The dose levels, the detailed escalation process and the final group assignment procedures are not reported in the registry record.

The study is recorded as single-group, with no allocation method and no masking. The listed dose groups do not constitute a randomized control comparison: the record explicitly cautions that the arms are not a like-for-like control comparison. Consequently, differences between those groups, if reported, would not by themselves establish an effect of dose or distinguish a treatment effect from other explanations.

The primary outcome is a participant count for successful engraftment, with a stated timeframe of 2 Months. Its definition refers to Day 2 (24H) Biore Strip samples. The relationship between that timeframe and the specified sampling time is not clarified in the registry record. Although the study is marked completed, completion status does not establish that every planned outcome was reported. The primary endpoint result and the number of participants included in its analysis are not reported in the registry record.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Successful Engraftment of Probiotic Following a Single Application., measured over 2 Months.

The primary endpoint is the number of participants with successful engraftment of the probiotic following a single application. It is a binary participant-level outcome: each participant either meets the stated success definition or does not. Success is defined using two assay ratios in Day 2 (24H) Biore Strip samples: deoR/PanBac and Cas5/PanBac must both be >40%.

The record explains that deoR and Cas5 identify loci associated, respectively, with a repressor of porphyrin production and a CRISPR-associated protein. PanBac is described as a locus found in nearly all bacteria on the face and serves as the denominator for calculating the proportion of bacteria containing the loci of interest. Thus, the endpoint operationalizes engraftment through assay measurements in hair follicles rather than through a direct clinical assessment of acne symptoms.

As a general statistical concept, a binary endpoint makes a prespecified threshold easier to interpret as a count of participants meeting a criterion. It also discards information about how far a measurement lies above or below that threshold. This endpoint could describe whether the assay-defined criterion was met, but it does not by itself establish clinical benefit, durability, or a causal treatment effect. The registry lists a timeframe of 2 Months while defining success using Day 2 (24H) samples; that timing is not reconciled in the registry record. The observed number meeting the criterion is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry’s primary outcome is a binary participant-level measure reported as a count. It classifies successful engraftment according to whether both assay ratios exceed the stated threshold. The record does not post the count meeting that definition, so no observed event proportion or confidence interval can be interpreted for the primary outcome.

What does a binary count tell readers?

As a general statistical concept, a binary outcome reduces each participant’s measurement to one of two categories, such as meeting or not meeting a threshold. A count is a direct description of how many participants fall into the category of interest. When the relevant denominator is also known, a proportion can describe the frequency of that category in the analyzed group. The registry record does not report the primary endpoint count or its analysis denominator, so neither the count nor the corresponding frequency can be stated.

Threshold-based outcomes can be useful when a study needs a clear classification rule. Here, the rule requires both deoR/PanBac and Cas5/PanBac to be >40% in the specified samples. But a threshold simplifies continuous assay measurements: values just on either side of a cutoff are classified differently even if they are close, while values far apart on the same side are grouped together. The underlying assay values and their distribution are not reported in the registry record.

Why does study design affect interpretation?

As a general statistical concept, randomization helps make comparison groups comparable on average by assigning participants through chance. A control group can then provide a reference for interpreting outcomes under an alternative condition. This study is recorded as single-group, with no allocation method or masking, and its dose groups are expressly not a like-for-like control comparison. The study can therefore describe observations after NB01 application if those observations are reported, but it cannot provide a randomized estimate of NB01 versus a control condition.

Open-label studies do not conceal the assigned intervention from participants or investigators. That feature can matter particularly for outcomes involving subjective judgment, although the stated primary endpoint relies on assay measurements. The registry record does not report blinding of laboratory personnel or other procedures that might affect measurement. It would be inappropriate to infer that such safeguards were or were not used.

How should uncertainty be understood?

As a general statistical concept, a confidence interval expresses the range of values reasonably compatible with the observed data under a specified method and assumptions. It communicates precision as well as the central estimate. A count from a small study can be compatible with a broad range of underlying event frequencies; an interval helps make that uncertainty visible. No primary endpoint estimate or interval is reported in the registry record, so the precision of the engraftment finding cannot be assessed.

For binary outcomes, methods for intervals and tests depend on the design and on the number of observed events. A one-group estimate would answer a descriptive question about the observed group, while a between-group test would address a comparison and require suitable groups and an analysis plan. The registry record does not post a primary endpoint analysis, p-value, confidence interval or comparison estimate. No inferential conclusion should be inferred from the endpoint definition alone.

What do the planning assumptions mean?

The registry describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial achieved a particular power or that the planned comparison was conducted. The record does not report the illustration’s numeric results, the observed primary endpoint effect, or a rationale for the study’s enrollment. Such planning figures cannot substitute for an observed outcome analysis.

As a general statistical concept, power is the probability that a specified design and analysis will detect an effect of a particular size under stated assumptions. It is not a measure of whether a result is true, nor does it describe the precision of an observed estimate. Sample-size calculations are prospective planning tools. They should not be presented as observed power after a study is complete. In this record, the planning illustration is especially difficult to connect to the trial because the primary endpoint result is not reported and the actual study is not a randomized two-arm comparison.

Over-dispersion is a general issue for count data when variability exceeds what a chosen probability model expects. It can make model-based standard errors too small if ignored. The primary endpoint is defined as a participant count for a binary outcome, not as a recurrent-event count. The registry does not report a model-based analysis or any indication that over-dispersion was assessed, so it is not possible to say that this issue arose in the analysis.

What analysis details are absent?

The registry record lists 0 analyses. It does not report the statistical test or estimation method for the primary endpoint, the analysis population, the handling of missing assay samples, or whether any covariates were used. It also does not report an interim analysis plan. Without those details and without the endpoint result, readers cannot reproduce or evaluate an inferential analysis. The transparent conclusion is limited to what is recorded: a defined assay threshold, a completed study listing and a missing primary outcome result.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Low Dose", "High Dose")
n      <- c(5, 5)
events <- c(2, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Low Dose  5  2  40.0  5.3  85.3  11.8  76.9  11.8  77.7
ARM  High Dose  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures, but it records 0 analyses. It does not report how many of those measures were designated primary, secondary or exploratory beyond the specific primary outcome identified in the record. The outcome list alone does not show which measures were analyzed or whether any results were selected for reporting.

Multiplicity arises when several outcomes, time points or comparisons are tested. As a general statistical concept, making many tests can increase the chance that at least one appears statistically significant by chance. Common approaches include prespecifying a hierarchy or adjusting the interpretation of tests; the appropriate choice depends on the study’s aims and analysis plan. A multiplicity strategy is not reported in the registry record. Because no analyses or primary endpoint result are posted, it is not possible to assess how multiplicity was handled or whether it affected interpretation.

Missing-data procedures are also not reported in the registry record. The endpoint depends on assay samples, but the record does not state whether all expected samples were available, how unusable or absent samples were classified, or whether participants with missing measurements were excluded from the endpoint denominator. The enrollment listing does not establish the number contributing endpoint data. Without these details, readers cannot determine whether the reported analysis, if any, represented all enrolled participants or a subset.

The analysis populations are not reported in the registry record. There is no description of an intention-to-treat, per-protocol or safety population for the primary endpoint. Nor is there a statistical plan describing exclusions or deviations. These absences matter because the definition of who is analyzed can change the interpretation of a participant count. The posted record does not permit an assessment of such choices.

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 non-serious adverse event terms

The safety record lists Low Dose and High Dose groups separately. For serious adverse events, each group has 5 participants at risk and 0 affected. Deaths are recorded as 0 in each group. For other adverse events, each group has 5 participants at risk and 1 affected. These are the recorded counts, not estimates of risk beyond the participants represented in the registry.

A count of 0 serious events means that no such event is recorded among the listed participants at risk in that group. It does not establish that the true chance of a serious event is zero, particularly in a small early-phase study. Likewise, the other adverse-event counts do not show which events occurred or whether they were considered related to NB01. Event descriptions, severity, timing, duration and attribution are not reported in the registry record.

The study is open label and lacks a control group suitable for a like-for-like safety comparison. The listed dose groups should therefore be read as descriptive group records, not as evidence that one dose is safer than another. The registry also lists no serious adverse-event terms. These figures provide a limited safety snapshot; they do not support broad claims about safety outside the recorded study.

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

The record establishes that a Phase 1 dose-escalating study of a single NB01 application in adults with moderate acne was listed as completed. It describes a primary endpoint based on assay-defined follicular engraftment and reports selected adverse-event counts by dose group. It does not report the primary endpoint result, so readers cannot determine how many participants met the engraftment criterion.

The endpoint is a biological assay measure. Meeting the stated threshold would indicate that both specified ratios exceeded the cutoff in the stated samples. By itself, that classification would not establish improvement in acne, persistence of engraftment, prevention of recurrence, or a causal clinical effect. The registry’s discussion of replacing disease-associated strains with health-associated strains is a proposed rationale, not a finding established by the posted results.

The design also does not support a direct comparison with placebo, no treatment or another intervention. It is recorded as a single-group, open-label study without a randomized control comparison. The Low Dose and High Dose arms are not described as equivalent comparison groups. Any difference between them would need cautious interpretation and cannot be treated as a randomized estimate of dose effect.

The safety counts show no serious adverse events and no deaths recorded in either listed group, alongside one other adverse event in each group. These observations are limited to the participants at risk recorded for this study. They cannot rule out uncommon or delayed events, and the registry does not report the event details needed to assess severity or attribution.

In short, the registry record documents a study design, an assay-based endpoint definition and limited safety counts, but not the primary outcome result or an inferential analysis. It therefore does not establish whether the endpoint was met, how precisely it was estimated, or whether NB01 changed clinical acne outcomes. Those questions remain unanswered by the posted results.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the gap between a clearly described endpoint and a reportable endpoint result. The registry defines successful engraftment using two assay ratios and a threshold, but does not report the number of participants meeting it. Without that result and its denominator, the main biological outcome cannot be summarized as an observed frequency or judged for precision.

The design also illustrates why a study’s stated objective and its comparison structure must be considered together. Dose escalation can be used to describe experience across dose levels, but the record identifies no randomized control group. The two listed dose groups are not a like-for-like comparison. A study can therefore address descriptive early-phase questions while leaving comparative efficacy questions unresolved.

The distinction between a biomarker or assay endpoint and a clinical outcome is important. The primary endpoint records an assay-defined criterion in follicular samples. It is not itself a measure of acne severity or a direct test of whether participants experienced clinical improvement. The registry lists clinical impact among the study aims, but the posted record does not provide a primary engraftment result or establish a clinical effect.

Finally, the safety counts show why small early-phase records should be read descriptively. Zero recorded serious events is useful information about the observed study experience, but it cannot rule out events that were not observed. A transparent account of denominators, event detail, missing measurements and analysis methods is essential for judging what a result can support. Those details and the primary outcome result are not reported in the registry record.

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 main limitation for interpretation is that the primary endpoint result is not reported in the registry record. The count of participants meeting the engraftment definition, the endpoint denominator and any uncertainty estimate are absent. Consequently, the stated primary question cannot be answered from the posted results.

The sampling time is also described in two ways: the primary outcome timeframe is listed as 2 Months, while the success definition refers to Day 2 (24H) Biore Strip samples. The record does not explain how these descriptions relate. This leaves uncertainty about the timing represented by the endpoint.

The study is open label and recorded as single-group, with no randomized allocation and no control group. The dose groups are not presented as like-for-like controls, and the record does not provide dose amounts or full escalation details. Thus, the design does not support a direct causal comparison of NB01 with an alternative condition or a reliable comparative interpretation of the dose groups.

Other important reporting details are absent: the number contributing primary endpoint data, missing-sample handling, analysis populations, statistical methods, multiplicity procedures and any interim analysis plan. The record lists 12 outcome measures and 0 analyses, but this does not reveal which outcomes were assessed or how they were interpreted. Safety reporting is also limited to counts; event types, severity, timing and attribution are not reported. These limitations constrain both the biological interpretation and any assessment of clinical relevance.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of the Safety, Engraftment, and Action of NB01 in Adults With Moderate Acne — NCT03450369.
• Registry record last updated 2020-08-03; status last verified 2020-07.
• Results first posted 2020-08-03.
• 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

NCT03450369 is a completed Phase 1 study, described as Phase 1B, of a single topical NB01 application in adults with moderate acne. It is recorded as open label, dose escalating and single-group, with an enrollment of 10. The registry lists Low Dose and High Dose groups but no randomized control comparison.

The primary outcome is the number of participants with successful engraftment, defined by both deoR/PanBac and Cas5/PanBac being >40% in Day 2 (24H) Biore Strip samples. The timeframe is listed as 2 Months. The observed primary endpoint result and its analysis denominator are not reported in the registry record.

Each dose group lists 0 serious adverse events and 0 deaths among 5 participants at risk, and 1 other adverse event among 5 participants at risk. The record lists 12 outcome measures and 0 analyses. Statistical methods for the primary outcome, missing-data handling, analysis populations and multiplicity procedures are not reported in the registry record.