A Study of RBT-1 in Healthy Volunteers and Subjects With Stage 3/4 Chronic Kidney Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of RBT-1 in Healthy Volunteers and Subjects With Stage 3/4 Chronic Kidney Disease (NCT03893799), a non-randomized phase 1 study. The primary outcome is Effect of RBT-1 on Plasma Ferritin Levels.

2. Clinical Question

3. Trial Design

The registry describes a completed Phase 1b, single-center, sequential dose-escalating study of RBT-1. Enrollment is reported as 54. The study included healthy volunteers and subjects with Stage 3/4 chronic kidney disease. Its stated aims were to assess safety, tolerability, pharmacokinetics, and pharmacodynamic effect. The listed intervention is RBT-1, with dose groups ranging from 9 mg SnPP/240 mg FeS to 90 mg SnPP/240 mg FeS.

Allocation was non-randomized and masking was none. These features matter when interpreting comparisons across dose groups. In general, random allocation helps balance measured and unmeasured participant characteristics across groups, while masking can reduce some influences on reporting or assessment. Without randomization or masking, observed differences between groups may reflect differences in participants, study conduct, or other factors as well as dose. The registry itself cautions that the arms are not a like-for-like control comparison.

A sequential design means that groups are studied in an ordered progression, but the registry record does not report the specific rules governing dose escalation, decisions between dose groups, or stopping criteria. It also does not report how participants were assigned to the healthy-volunteer and chronic-kidney-disease populations within the dose groups. Those details should not be inferred from the dose labels alone.

The record lists the study start date as 2019-08-27, primary completion as 2020-04-22, and status as completed. It does not report a randomized treatment comparison or a control arm. The registry record does not report the protocol’s statistical plan, sample-size justification, interim analyses, or prespecified criteria for escalation. Accordingly, the available design details support a description of the study’s structure, but not a reconstruction of its operational or statistical decision process.

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: It was pre-specified to analyze healthy volunteers and participants with CKD Stage 3/Stage 4 together and report results by dose.

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 Effect of RBT-1 on Plasma Ferritin Levels, measured over 24 hours post-infusion.

The primary outcome measure is the effect of RBT-1 on plasma ferritin levels. It is defined as percent change from baseline, assessed at 24 hours post-infusion, and summarized using a least-squares mean with a 95% confidence interval. The registry record does not report a numerical estimate or confidence interval for this outcome.

In general, measuring change from baseline describes how a participant’s value differs from their own starting value, expressed as a percentage. Plasma ferritin is the specified biomarker; the registry frames this measure as part of evaluating pharmacodynamic effect. The record does not state why this particular time point or biomarker was selected, so a more specific rationale is not reported in the registry record.

A least-squares mean is generally a model-based mean that may account for factors included in a statistical model. The record does not describe the model or list the factors used to calculate the least-squares mean. A 95% confidence interval communicates the statistical uncertainty around an estimate under the assumptions of the analysis. It is not reported for the outcome in the results available in the registry record, so the endpoint’s estimated magnitude and precision cannot be evaluated.

The registry record does not provide a numerical baseline value, a numerical change, or a comparison between dose groups for this primary outcome. The endpoint definition therefore identifies what was intended to be measured, but it does not establish what was observed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a least-squares mean percent change from baseline in plasma ferritin levels, with a 95% confidence interval, at 24 hours post-infusion. It does not report the numerical estimate, interval limits, statistical model, or analysis population. The terms below explain the general statistical ideas; they do not imply that any particular method beyond the reported summary was used.

What does percent change from baseline describe?

In general, a change-from-baseline outcome compares a follow-up measurement with a participant’s starting measurement. Expressing the change as a percentage relates it to the baseline value rather than describing only an absolute-unit difference. The registry specifies the 24-hour post-infusion time point. It does not provide the baseline or follow-up values, the rule for handling missing measurements, or a numerical result for the percentage change. As a result, the definition can be described, but the observed pattern cannot.

What is a least-squares mean?

In general, a least-squares mean is an estimate derived from a statistical model. Depending on the model, it may adjust for specified characteristics or account for the structure of the data. It is not necessarily identical to a simple arithmetic average. The registry names a least-squares mean but does not report the model formula, the factors included, the method used to estimate uncertainty, or whether the same model was applied across populations and dose groups. No adjusted interpretation can be reconstructed without those details and the numerical results.

How should a confidence interval be read?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical method. A narrower interval indicates greater statistical precision than a wider interval for the same estimand and analysis framework. The confidence level stated for this endpoint is 95%. The registry record does not give the interval limits, so its width and the range of values consistent with the estimate cannot be assessed. A confidence interval does not by itself establish clinical importance or remove potential bias from the study design.

Why does the design matter for dose-group comparisons?

In general, random allocation helps make groups comparable by distributing participant characteristics without relying on investigator choice or study sequence. Masking can limit some influences on treatment delivery, reporting, and outcome assessment. This study was non-randomized and unmasked, and the registry says its arms are not a like-for-like control comparison. Thus, any difference between groups, if reported elsewhere, would need to be interpreted with those design features in mind. The registry record does not report a comparative analysis for the primary endpoint.

The record calls the study sequential and dose-escalating. In general, such a structure studies dose groups in sequence, but the details of how decisions are made between groups depend on the protocol. The escalation rules, review procedures, and any stopping criteria are not reported in the registry record. It would be inappropriate to infer them from the dose levels or from the fact that the study is complete.

What can the adverse-event counts establish?

In general, adverse-event counts describe events recorded during a defined period and in a defined analysis population. The registry lists the number at risk and the number affected for serious and other adverse events in each dose group. It reports zero serious adverse events in each listed group. For other adverse events, the listed affected counts differ across groups. These counts do not by themselves show whether groups differed because the study was non-randomized, and the record does not provide the event terms or additional context needed to interpret those counts fully. A count of participants affected also does not describe the severity, timing, duration, or relationship of each event unless those details are separately reported.

Can the sample-size illustrations be interpreted?

In general, a planning illustration uses assumptions about a target effect, significance level, allocation, and statistical method to show what a future study might require. Such a calculation is not observed power and does not establish that a completed study had a particular probability of detecting an effect. The registry describes its planning illustration as based on an observed effect and states assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that the target effect is a stated fraction of the observed effect. Because the numerical observed primary endpoint effect and corresponding planning outputs are not reported in the registry record, the illustration cannot be assessed or used to infer precision for this study.

More broadly, the registry record does not report the statistical analysis plan, details of any interim analyses, handling of missing observations, or analysis populations. Those omissions prevent a fuller appraisal of model assumptions, multiplicity procedures, and sensitivity analyses. The distinction is important: the registry identifies the intended outcome summary, but it does not provide enough information to independently reproduce or verify that analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures, but it does not report a multiplicity strategy. Multiplicity refers, in general, to the increased chance of a false-positive finding when several outcomes, groups, time points, or statistical tests are considered. A prespecified hierarchy or adjustment can address that issue, but no such procedure is reported in the registry record. The record also lists zero analyses, so it does not provide test results or a reported analysis set against which to evaluate multiplicity.

Missing-data handling is not reported in the registry record. The record does not state how participants with an unavailable 24-hour plasma ferritin measurement were handled, whether any values were excluded, or whether any imputation or sensitivity analysis was used. It also does not describe the approach to missing safety follow-up. These details matter in general because missing measurements can affect both the estimate and its uncertainty, particularly when the reasons for missingness differ across participants or groups.

The analysis populations are not reported in the registry record. It is not stated which participants contributed to the primary endpoint analysis, whether the analysis used all enrolled participants or a defined subset, or how population membership was determined. The registry reports enrollment of 54, but the available record does not provide a flow of participants through treatment and analysis. Therefore, the reported enrollment cannot be treated as the denominator for the primary endpoint.

The registry record also does not describe the statistical plan, model covariates, or interim analyses. These omissions do not show that the procedures were absent; they mean that they are not documented in the registry record. Without these details and the numerical endpoint results, readers cannot assess whether the reported analysis followed a prespecified approach or how sensitive its findings were to alternative assumptions.

11. 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 registry’s serious adverse-event fields report zero participants affected in each listed dose group: 9 mg SnPP/240 mg FeS, 27 mg SnPP/240 mg FeS, 45 mg SnPP/240 mg FeS, 63 mg SnPP/240 mg FeS, and 90 mg SnPP/240 mg FeS. The corresponding numbers at risk are 6, 18, 6, 6, and 18. The record reports no deaths in the listed groups.

For other adverse events, the registry reports 0 participants affected in the 9 mg SnPP/240 mg FeS group, 6 in the 27 mg SnPP/240 mg FeS group, 1 in the 45 mg SnPP/240 mg FeS group, 5 in the 63 mg SnPP/240 mg FeS group, and 12 in the 90 mg SnPP/240 mg FeS group. These are group-specific counts, not a randomized comparison. The study was non-randomized, and its arms are not a like-for-like control comparison.

In general, a count of participants affected does not convey the event’s type, duration, severity, timing, or relationship to treatment. The registry’s listed serious-event terms are empty, and further event descriptions are not reported in the registry record. Zero recorded serious events in these groups should be read as a description of the posted counts, not as evidence that serious risks are absent.

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

The registry record establishes that a completed Phase 1b study evaluated RBT-1 in healthy volunteers and subjects with Stage 3/4 chronic kidney disease, using a sequential dose-escalation design. It identifies plasma ferritin percent change from baseline at 24 hours post-infusion as the primary outcome and specifies a least-squares mean with a 95% confidence interval. It does not report the numerical result for that outcome.

Without the estimate and its confidence interval, the magnitude, direction, and precision of the primary endpoint cannot be assessed. The available information also does not show how the endpoint behaved across dose groups or between the two participant populations. A description of the intended measurement is not a finding about what the measurement showed.

The record does report serious adverse-event counts of zero in each listed dose group and reports group-specific counts for other adverse events. Those counts are descriptive. Because allocation was non-randomized and masking was absent, differences in counts across groups should not be interpreted as causal effects of dose. The record does not provide the event terms and contextual details needed for a fuller account of the safety observations.

In general, a small early-phase study can characterize measurements and observed events under the study conditions, but interpretation depends on the analysis, participant composition, follow-up, and uncertainty. The registry record does not report enough detail to assess those features fully. It also does not report a randomized control comparison, and explicitly cautions that the arms are not a like-for-like comparison.

These limits do not establish that no further analyses or results exist outside the registry. They mean only that the posted registry record does not support conclusions about the primary endpoint’s numerical result, its precision, or a causal comparison among dose groups. No treatment recommendation follows from the descriptive design and counts alone.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of how an early-phase dose-escalation design differs from a randomized comparison. The registry identifies a sequential structure, non-randomized allocation, no masking, and multiple dose groups. Those details shape the questions that the data could address and the limits on interpreting group differences. The registry itself cautions that the groups are not a like-for-like control comparison.

The primary outcome is defined in a way that signals a model-based summary: a least-squares mean percent change in plasma ferritin from baseline, with a 95% confidence interval, at 24 hours post-infusion. This makes clear why outcome definitions and estimates need to be read together. The record specifies the measure and summary but does not report the estimate, interval, or model details. Readers therefore cannot assess the result’s magnitude, uncertainty, or reproducibility from the registry record.

The safety counts also illustrate the difference between descriptive reporting and comparative inference. The record lists serious and other adverse-event counts by dose group, but the non-randomized design does not support treating differences as randomized dose effects. Event definitions and additional details are not reported in the registry’s serious-event summary, further limiting interpretation.

Finally, the record demonstrates the value of complete statistical reporting. Analysis populations, missing-data procedures, multiplicity strategy, and the statistical plan are not reported. Their absence from the registry entry leaves important questions unanswered, without proving that such procedures were not used elsewhere. For clinical researchers and biostatisticians, the key lesson is to distinguish what the design and registry metadata specify from what the numerical results and analysis details would be needed to establish.

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 is that the registry record does not report numerical results for the primary endpoint. Although it identifies the outcome, time point, summary measure, and confidence level, it gives no least-squares mean estimate or confidence interval. The observed magnitude and precision therefore cannot be evaluated.

The study was non-randomized, unmasked, and sequential. The registry explicitly cautions that the arms are not a like-for-like control comparison. The record does not describe allocation procedures, escalation rules, or criteria for moving between doses. Comparisons across dose groups, if available elsewhere, would need to be interpreted in light of these design features.

The participant populations include healthy volunteers and subjects with Stage 3/4 chronic kidney disease, but group-level population composition is not reported. The registry does not explain how participants from these populations were distributed among dose groups. It also does not report participant flow, endpoint analysis populations, or the handling of missing measurements.

Further limitations in interpreting the posted record include the absence of a reported statistical plan, model details, multiplicity procedures, and information about interim analyses. The listed serious adverse-event terms are empty, and the registry does not provide detailed descriptions for the other adverse-event counts. These gaps restrict interpretation of both efficacy-related measurements and safety observations. They should be understood as limitations of what is reported in the registry record, not evidence that additional information does not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of RBT-1 in Healthy Volunteers and Subjects With Stage 3/4 Chronic Kidney Disease — NCT03893799.
• Registry record last updated 2025-08-07; status last verified 2025-07.
• Results first posted 2025-08-07.
• 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.

18. Record Summary

The registry record describes a completed Phase 1b, single-center, sequential dose-escalation study of RBT-1 in healthy volunteers and subjects with Stage 3/4 chronic kidney disease. Enrollment is reported as 54. Allocation was non-randomized and masking was none.

The primary outcome is least-squares mean percent change from baseline in plasma ferritin at 24 hours post-infusion, with a 95% confidence interval. Its numerical result is not reported in the registry record. The record lists three outcome measures and zero analyses.

Serious adverse events affected zero participants in each listed dose group; the record also gives group-specific counts for participants affected by other adverse events. The study status is completed. The record does not report the statistical plan, analysis populations, missing-data methods, or multiplicity procedures.