AB1 in Adult Patients With Sickle Cell Disease (SCD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AB1 in Adult Patients With Sickle Cell Disease (SCD) (NCT05261711), a na phase 1, phase 2 study. The primary outcome is Total Number of Adverse Events/Serious Adverse Events as Measured by Patient Report/Medical Records.

2. Clinical Question

In statistical terms, the record describes a safety-focused early-phase investigation with dose escalation, rather than a controlled test of treatment benefit. The primary question concerns the burden of adverse events recorded during the stated observation period. The listed pharmacokinetic outcomes address how AB1 behaves in the body; they do not by themselves establish whether a clinical outcome improves.

The design can describe events observed during treatment and follow-up in the listed cohorts. It cannot separate an AB1 effect from other explanations using a randomized control comparison, because no such comparison is listed. Nor does the registry record report outcome estimates that would support a conclusion about clinical effectiveness. The study status is terminated, so the record should be read as a description of the reported design and safety information, not as a complete account of every planned cohort or outcome.

3. Trial Design

This is a Phase 1/2, open-label, dose-escalation study of AB1 in adults with sickle cell disease. The registry record describes a sequential model and lists allocation as not applicable. Participants and investigators were not masked to treatment. No control arm is listed, so the dose cohorts are not randomized comparison groups.

The planned starting dose was 2 mg. The brief summary describes up to 6 additional cohorts at 4 mg, 8 mg, 10 mg, 12 mg, 16 mg, and 32 mg. In each dose-escalation cohort, AB1 was to be taken orally once daily for 8 weeks. These details describe the plan; the record does not establish that every planned dose cohort was enrolled.

The safety information lists cohorts at 2 mg, 4 mg, 8 mg, and 10 mg. No safety group is listed for the planned 12 mg, 16 mg, or 32 mg doses. The registry enrollment is 16. The record gives a study start date of 2022-12-05 and a primary completion date of 2024-10-01, and lists the study status as terminated.

The primary outcome is a count of adverse events and serious adverse events, as measured by patient report or medical records from consent up to 12 months. Secondary outcomes include changes in pharmacokinetic measures such as Cmax, Tmax, half-life, AUC, clearance, and volume of distribution. The record lists 13 outcome measures overall, but does not give numerical results for the primary outcome or these pharmacokinetic measures in the registry record described. A detailed statistical analysis plan and the reasons for termination 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.

Before assignment: All patients were assigned to a treatment arm cohort, and upon completion, following a washout, given the opportunity to be re-enrolled to a subsequent higher dose cohort. Three participants were screen failures.

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 Total Number of Adverse Events/Serious Adverse Events as Measured by Patient Report/Medical Records, measured over From the time of consent up to 12 months.

The primary endpoint is the total number of adverse events and serious adverse events measured by patient report or medical records. The stated timeframe runs from consent up to 12 months. A count endpoint captures the frequency of events recorded over that period, rather than describing only whether a participant experienced at least one event.

That distinction matters because one participant may experience more than one event. A total count can therefore reflect both how many participants report an event and whether events recur. The registry record does not report how recurrent events were handled in the primary analysis, how events were attributed to treatment, or how observation time was addressed if it differed between participants.

In general, early-phase dose-escalation studies use safety outcomes to describe tolerability and identify events requiring careful monitoring as doses increase. This is a general explanation of the purpose of such outcomes, not a claim about a particular decision rule in this trial. The registry record does not report a dose-escalation stopping rule or a statistical threshold for acceptable safety.

The primary endpoint should not be conflated with the posted cohort safety counts. The primary endpoint is defined as a total number of events over a stated timeframe. The safety information separately reports participants at risk and participants affected by serious or other adverse events in the listed dose groups. Those cohort counts provide a limited safety description, but they do not supply a complete numerical result for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a sequential dose-escalation design and lists no statistical analyses. The explanation below distinguishes what the record says from general statistical principles; it does not infer an analysis plan that is not reported.

What does a sequential design imply?

In a sequential design, participants enter cohorts in an ordered process rather than being allocated randomly across concurrent treatment groups. Here, the planned sequence begins at 2 mg and describes higher doses of 4 mg, 8 mg, 10 mg, 12 mg, 16 mg, and 32 mg. The listed safety groups cover the 2 mg, 4 mg, 8 mg, and 10 mg cohorts. Because dose and enrollment sequence are linked, differences between cohorts cannot be attributed to dose alone on the basis of these counts.

General explanation: randomization helps balance measured and unmeasured characteristics between comparison groups on average. It is not part of the design described in this record. Sequential escalation may be appropriate for early-phase questions about administering increasing doses, but it does not provide the same basis for estimating a treatment contrast as a randomized trial.

How should a count endpoint be understood?

The primary endpoint is the total number of adverse events and serious adverse events, measured through patient report or medical records. A count records events, not merely the number of people who experienced at least one event. Repeated events in the same participant can affect the total, so interpreting a count requires clarity about event definitions, recurrence, and the observation period. The stated timeframe is from consent up to 12 months. The record does not report whether the primary analysis counted repeated events separately, how missing follow-up was handled, or whether time at risk differed across participants.

General explanation: count data are often analyzed with methods that reflect their distribution and the relationship between the mean and variability. A Poisson model is one general approach when its assumptions fit. If the observed variability exceeds what that model allows, over-dispersion may make standard errors too small unless accounted for. Other approaches may be appropriate depending on the data structure. None of these methods should be attributed to this study: the registry record does not report the primary analysis method, model assumptions, or a dispersion parameter.

What is the role of uncertainty?

Any estimate from a small cohort is subject to sampling uncertainty. A confidence interval is a general way to show a range of values compatible with the observed data under a specified statistical method. Narrow intervals indicate greater precision under that method; wide intervals indicate less precision. The registry record does not report confidence intervals for the posted safety counts, so their precision cannot be quantified from the stated information.

General explanation: statistical significance and clinical importance are different ideas. A result can be statistically uncertain without demonstrating that an effect is absent, and an estimated difference can be important to a clinical question even when it is imprecise. In this record, no controlled treatment-effect estimate or inferential result is reported, so there is no basis for a significance claim about comparative treatment effects.

What do sample-size illustrations mean?

Any sample-size figures associated with the posted results are planning illustrations computed from an observed effect, not the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event settings, the illustration concerns a total number of events; for other settings, it concerns participants per arm for 80% power or another stated power level.

General explanation: a planning calculation asks how much information a future study might need under selected assumptions. It does not describe the number of participants actually analyzed, prove that the original study had a particular probability of detecting an effect, or show that the assumed effect is reliable. Because this is a sequential, nonrandomized study with no listed control arm, equal allocation between two arms is an illustrative assumption rather than a description of the trial design. Sample-size illustrations are not observed power.

What can be said about the listed safety counts?

The record reports the numbers at risk and affected for serious and other adverse events in the listed dose groups, along with zero deaths in each listed group. These are descriptive safety data. General explanation: a count of participants affected answers a different question from a count of all events. A participant can potentially experience multiple events, so event counts and affected-participant counts need not be interchangeable. The registry record does not state how the cohort safety summaries relate to the primary total-event endpoint.

The record lists no analyses. This means that the registry information does not include a specified inferential method, adjusted estimate, or uncertainty interval for the outcomes. It does not establish that investigators performed no analyses outside the registry. The analysis populations, rules for excluding observations, handling of incomplete data, and methods for accounting for the sequential design are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures, including a primary safety outcome and secondary pharmacokinetic measures. The secondary outcomes named in the record include changes in Cmax, Tmax, half-life, AUC O-t, dose-normalized AUC O-inf, clearance, volume of distribution, and Vss. Assessing many outcomes can raise a multiplicity issue: when several hypotheses are tested, the chance of at least one apparently unusual result can increase. This is a general statistical concern, not a claim that the trial used a particular testing strategy.

A multiplicity plan might specify which endpoint is primary, the order in which endpoints are tested, or a method for adjusting inference across outcomes. The primary outcome is identified, but the record does not report a procedure for controlling multiplicity, a hierarchy for secondary outcomes, or which outcomes were included in confirmatory testing. The registry record lists no analyses, so no inferential testing plan can be reconstructed from it.

Missing-data methods and analysis populations are also not reported in the registry record. It does not say how participants with incomplete follow-up were treated, whether all enrolled participants were included in each outcome analysis, or how deviations from the planned dosing schedule were handled. The stated observation window for the primary outcome is from consent up to 12 months, but the record does not describe completeness of event ascertainment during that period.

These omissions limit interpretation of both the count endpoint and the pharmacokinetic outcomes. They do not show that data were missing or that a particular analysis was inappropriate; they mean that the registry information does not document the relevant methods. Conclusions about robustness, selective reporting, or the impact of missing observations cannot be drawn from the record alone.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (50.0%), vaso-occlusive crisis (50.0%), acute infectious diarrhea (25.0%), drug reaction with eosinophilia and systemic symptoms (dress) (25.0%), sickle cell pain crisis (25.0%).

The safety information reports participants at risk and participants affected by serious and other adverse events within each listed dose cohort. At 2 mg, the record lists 2 at risk, 1 affected by a serious adverse event, and 2 affected by other adverse events. At 4 mg, it lists 2 at risk, 1 affected by a serious adverse event, and 1 affected by other adverse events. At 8 mg, it lists 5 at risk, 2 affected by a serious adverse event, and 5 affected by other adverse events. At 10 mg, it lists 4 at risk, 3 affected by a serious adverse event, and 4 affected by other adverse events. No deaths are reported in these groups.

These counts should be read within their respective cohorts. They are not a randomized comparison, and the same participant could potentially be counted among those affected by both serious and other adverse events. The record does not define the relationship between these categories or give event totals for each group. It also does not report safety counts for the planned 12 mg, 16 mg, or 32 mg cohorts.

The listed serious-event terms include Pneumonia and Vaso-Occlusive Crisis at 50.0% each; Acute Infectious Diarrhea, DRESS, and Sickle Cell Pain Crisis at 25.0% each; and E. Coli Colitis at 20.0%. The denominator and any overlap among terms are not reported in the registry record. These percentages are not a substitute for the cohort-level counts or a comparative risk estimate.

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

The record establishes that AB1 was studied in an open-label, sequential dose-escalation design in adults with sickle cell disease, with a planned starting dose of 2 mg and higher dose cohorts described up to 32 mg. It documents safety groups at 2 mg, 4 mg, 8 mg, and 10 mg, with the numbers at risk and affected by serious and other adverse events. It also identifies a primary count endpoint and a set of pharmacokinetic outcomes.

Those details do not establish whether AB1 improves any clinical outcome. The registry record lists no randomized control group and no comparative treatment-effect estimate. The posted safety counts are descriptive observations in small cohorts, not proof that one dose is safer or more hazardous than another. Because enrollment was sequential rather than randomized across doses, changes between cohorts could reflect factors other than dose.

The primary outcome is a total number of adverse events and serious adverse events through 12 months, but a numerical result for that endpoint is not reported in the information summarized by the registry record. The safety counts for participants affected by events are not equivalent to a full event-count result. The record also does not report numerical pharmacokinetic estimates, confidence intervals, or statistical analyses.

The study status is terminated. That status alone does not explain why the study ended, whether planned enrollment was completed, or whether termination was related to safety, feasibility, funding, or another factor; those reasons are not reported in the registry record. The planned higher-dose cohorts have no listed safety groups in the available record.

General statistical interpretation: absence of a reported comparative result is not evidence that there was no effect, and descriptive event counts cannot establish a treatment effect. The appropriate reading is limited to the design and the observations actually recorded. Further conclusions about efficacy, dose-response, or safety beyond the listed groups would require information not reported in the registry record.

13. Why This Trial Matters Statistically

This trial matters statistically because early-phase dose escalation poses a different question from a conventional randomized comparison. The design is sequential and open-label, and the record lists no control group. Its observations can describe safety and pharmacokinetic outcomes during the study, but the design does not isolate the effect of AB1 from other explanations in the way a randomized comparison is intended to do.

The primary endpoint is an event count, while the posted safety figures report affected participants within dose cohorts. Distinguishing events from people affected is important: recurrent events can contribute more than once to an event total, whereas an affected-participant count does not convey recurrence. The registry record does not explain how these summaries relate to each other, so readers should avoid treating them as interchangeable measures.

The small numbers at risk in the listed cohorts also illustrate why precision matters. When cohorts contain few participants, a small change in the observed count can substantially change the descriptive picture. The record does not report confidence intervals or a statistical analysis for these safety counts, so their uncertainty cannot be quantified from the registry information.

Finally, the registry record lists 13 outcome measures, but no analyses. This makes it important to distinguish outcome definitions from outcome results and to distinguish planning illustrations from observed evidence. A statistical plan, missing-data approach, multiplicity strategy, numerical primary outcome result, and reason for termination are not reported in the registry record. Recognizing these boundaries helps keep descriptive safety information from being interpreted as a controlled estimate of benefit or harm.

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 describes the intended dose sequence, but safety groups are listed only for 2 mg, 4 mg, 8 mg, and 10 mg. Although the planned doses also include 12 mg, 16 mg, and 32 mg, no safety groups for those doses are reported in the information. The record does not explain whether those cohorts were not enrolled, were enrolled without posted safety summaries, or were affected by another circumstance.

The study is listed as terminated, but the reason for termination is not reported in the registry record. Enrollment is listed as 16, while the safety groups identify the numbers at risk separately; the registry record does not explain the relationship between these figures or provide a participant flow account. The start date is 2022-12-05 and the primary completion date is 2024-10-01, but the record does not describe follow-up completeness for the primary outcome.

The endpoint is defined as a total number of adverse events and serious adverse events, but the posted safety information reports affected participants. The registry record does not provide the numerical primary endpoint result or clarify recurrent-event counting, attribution, exposure time, or event ascertainment procedures. Nor does it report numerical pharmacokinetic results, uncertainty intervals, or analyses.

Open-label conduct and lack of a concurrent control group limit causal interpretation. Cohorts were sequential, so dose comparisons may also reflect differences in participants or study timing. Detailed eligibility criteria, baseline characteristics, analysis populations, missing-data methods, multiplicity procedures, and the statistical analysis plan are not reported in the registry record. These limitations restrict interpretation; they do not establish that any particular bias or data problem occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: AB1 in Adult Patients With Sickle Cell Disease (SCD) — NCT05261711.
• Registry record last updated 2026-10-15; status last verified 2026-09.
• Results first posted 2026-10-15.
• 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 NCT05261711, a Phase 1/2, open-label, sequential dose-escalation study of AB1 in adults with sickle cell disease. AB1 was planned as an oral, once-daily treatment for 8 weeks in each dose cohort, starting at 2 mg, with higher planned doses through 32 mg. The record lists an enrollment of 16 and a status of terminated.

The primary outcome is the total number of adverse events and serious adverse events, measured by patient report or medical records from consent up to 12 months. Safety groups are listed for the 2 mg, 4 mg, 8 mg, and 10 mg cohorts. No control arm is listed, and the design does not support a randomized comparison.

The registry record lists pharmacokinetic secondary outcomes but does not report numerical results for the primary endpoint, statistical analyses, or reasons for termination. The available safety counts are descriptive and apply only to the listed groups.