This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Dose Finding Study of DTX101 (AAVrh10FIX) in Adults With Moderate/Severe to Severe Hemophilia B (NCT02618915), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02618915 |
| Phase | Phase 1, Phase 2 |
| Condition | Hemophilia B |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ultragenyx Pharmaceutical Inc |
| Results posted | Yes |
2. Clinical Question
Population
Adult males with moderate/severe to severe hemophilia B were eligible. The study enrolled 6 participants, and its safety population was defined as participants who received DTX101, including anyone who received a partial dose or had a failed infusion.
Intervention
DTX101 was administered as a single peripheral intravenous infusion. Cohort 1 received 1.6 x 10^12 genome copies (GC)/kg; Cohort 2 received 5.0 x 10^12 GC/kg.
Comparator
There was no randomized control group. The two dose cohorts were not a like-for-like control comparison: allocation was non-randomized, and the study used a single-group model.
Primary question
The primary outcome counted participants with adverse events (AEs), treatment-related adverse events (TEAEs), and serious adverse events (SAEs) over the specified post-dose follow-up. The registry record does not report a comparative efficacy question.
The study’s central clinical question was whether administration of DTX101 was accompanied by adverse events in adults with moderate/severe to severe hemophilia B, and whether the recorded safety experience differed descriptively between the two dose cohorts. The dose-finding aspect is reflected in the two single-dose cohorts, but the registry record does not report a formal dose-response analysis or a statistical comparison between them.
The listed secondary outcomes include annualized bleeding rate, change from baseline in factor IX (FIX) activity over time, and use of FIX replacement therapy. They also include FIX inhibitors, cell-mediated immune response to FIX, and responses to two quality-of-life questionnaires. These outcomes indicate the range of clinical and laboratory measures registered for the study; outcome analysis results are not reported in the registry record.
Because the study was open-label, non-randomized, and had no control arm, its posted cohort counts describe the experience of the enrolled participants. They do not establish what would have occurred under another treatment or without DTX101.
3. Trial Design
This was a Phase I/II, open-label, non-randomized, single-group study with dose-finding objectives. The registry lists an enrollment of 6. Participants were adult males with moderate/severe to severe hemophilia B. DTX101 was given as a single peripheral intravenous infusion, with Cohort 1 receiving 1.6 x 10^12 GC/kg and Cohort 2 receiving 5.0 x 10^12 GC/kg.
Neither participants nor study personnel were masked, and assignment was not randomized. The cohorts therefore provide descriptive observations at two dose levels rather than a controlled comparison. The record does not report the method used to assign participants to cohorts, or whether any other design features were intended to support a dose comparison.
The study began on 2015-12-16, and the primary completion date was 2017-10-18. Its status is terminated. The reason for termination is not reported in the registry record. The stated safety follow-up extended up to 52 weeks after dosing for Cohort 1 or 44 weeks after dosing for Cohort 2; these are cohort-specific maximum timeframes, not evidence that every participant completed the full duration.
The primary outcome was the number of participants with AEs, TEAEs, and SAEs. The registry defines an AE as an untoward medical occurrence from informed consent through exit from the study, regardless of its causal relationship to study treatment. A TEAE was an event absent before exposure, or an existing event that worsened in severity or increased in frequency after exposure. The safety population included participants who received DTX101, including those with a partial dose or failed infusion.
The registry record does not report a sample-size justification, detailed cohort-allocation procedures, or a statistical analysis plan. Those details should not be inferred from the Phase I/II label or from the listed outcomes.
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 | DTX101, Cohort 1 | DTX101, Cohort 2 |
|---|---|---|
| STARTED | 3 | 3 |
| COMPLETED | 3 | 3 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Set: all participants who received DTX101 including participants who received a partial dose or failed infusion.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | DTX101, Cohort 1 | DTX101, Cohort 2 | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 3 | 6 | |
| Age, Customized: 18-49 years | participants | 0 | 3 | 3 |
| Age, Customized: 50-84 years | participants | 3 | 0 | 3 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 3 | 3 | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 3 | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Factor IX (FIX) Activity | IU/dL | 1.67 (SD 0.577) | 0.87 (SD 0.709) | 1.27 (SD 0.566) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs), measured over up to 52 weeks after dosing (Cohort 1) or 44 weeks after dosing (Cohort 2).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a participant count: the number of participants experiencing AEs, TEAEs, and SAEs. These categories capture different aspects of safety. An AE is defined broadly and does not require a causal relationship to treatment. A TEAE is classified by its timing or worsening after exposure. An SAE is a separate seriousness classification; the registry excerpt does not provide its full definition.
Counting participants is useful in an early dose-finding safety study because it records how many people experienced events, rather than treating multiple events in one person as though they came from different participants. The measure can therefore give a simple description of how widely an event category occurred among those who received study product. It does not, by itself, describe the number of events per participant, their duration, their severity beyond the serious classification, or whether DTX101 caused them.
The endpoint’s timeframe was up to 52 weeks after dosing for Cohort 1 or 44 weeks after dosing for Cohort 2. Because the follow-up periods differed, the cohort counts should be read with those timeframes in mind. The registry record does not report the actual follow-up completed by each participant or separate primary-outcome counts for AEs and TEAEs. Those values are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety figures describe 3 participants at risk in each cohort. In Cohort 1, 1 participant had a serious adverse event; in Cohort 2, 0 participants had a serious adverse event. The record also lists 3 participants with other adverse events in each cohort. No deaths are listed in either cohort. These are counts from a very small study, and each individual observation represents a substantial part of the cohort’s experience. They should be read as descriptive counts, not as stable estimates of event frequency.
The record lists musculoskeletal and connective tissue disorders as a serious-event term at 33.3%. This category-level figure does not establish a cause, identify the clinical course, or show whether the event was related to DTX101. The registry’s general AE definition explicitly includes events regardless of causal relationship. The event-specific relationship to treatment is not reported in the registry record.
The two cohorts are not randomized arms and are not a like-for-like control comparison. Their counts cannot isolate a dose effect: the registry does not report random allocation, and the cohorts may differ in ways that the posted figures do not capture. The cohort-specific follow-up windows also differ. No inferential comparison between the doses is reported in the registry record.
The study lists 10 outcome measures, including bleeding, FIX activity, replacement therapy, immune responses, and quality-of-life questionnaire responses. However, the registry record lists 0 analyses. Numerical results for those outcomes, and formal analysis results for the primary endpoint, are not reported in the registry record. The available safety counts therefore cannot be used to characterize the unreported outcomes.
Precision is limited by the small number of participants. A count such as 0 serious events in Cohort 2 does not demonstrate that serious events cannot occur; it means none were recorded among the 3 participants in that cohort over the reported study follow-up. Likewise, the count in Cohort 1 is an observation in that cohort, not a reliable estimate for a broader population. No confidence intervals or adjusted estimates are reported in the registry record.
The study status is terminated, but the reason is not reported in the registry record. Termination alone does not explain the safety observations or indicate why the study ended. Interpretation should remain limited to the posted participant counts and the definitions and follow-up periods recorded for the study.
9. Statistical Methods Explained
The registry identifies the primary outcome as a binary participant-level measure: whether a participant is counted as having an event in a specified category. This is different from an event-rate measure, which would count repeated events or account for time at risk. The posted safety figures are counts of participants, so they should not be interpreted as the total number of events.
What does a participant count tell us?
A participant count answers how many people in a defined safety population had an event classification. The denominator matters: the record lists 3 participants at risk in each cohort. With such small groups, a count can change visibly with the experience of a single participant. The counts are therefore informative as a description of these participants, but they provide limited precision for estimating how often events might occur in a larger population.
The categories also need to be kept distinct. The AE definition covers untoward medical occurrences regardless of relationship to study treatment. TEAEs are identified by timing or worsening after exposure. Seriousness is another classification, and serious events are not synonymous with events caused by treatment. The registry record provides the definitions of AEs and TEAEs but does not provide the full SAE definition in this record.
Why does the design matter?
Random allocation can help make treatment groups comparable, on average, by distributing measured and unmeasured characteristics across groups. This study was non-randomized, open-label, and described as a single-group study with two dose cohorts. Its cohorts are not a randomized control comparison. Differences in their observed counts cannot be attributed to dose alone using the posted information.
Open-label means masking was absent. Knowledge of treatment assignment can influence some aspects of event recognition or reporting, although the registry record does not describe whether or how that occurred in this study. The absence of a control group also means the safety counts do not show how many events would have occurred in a comparable group without DTX101.
How should uncertainty be understood?
A confidence interval is a range of values that, under a specified statistical method, expresses uncertainty around an estimate. In general, estimates based on few participants tend to be imprecise. The registry record does not report confidence intervals for the safety counts, so no interval-based precision claim can be made from the listed figures.
Over-dispersion is a general issue that can arise when event counts vary more than a statistical model assumes. It is relevant to analyses of counts or rates, particularly when outcomes cluster within people or vary across participants. The primary outcome is a participant count, and no count model, rate model, or over-dispersion adjustment is reported in the registry record. It would be inappropriate to assume that such a method was used.
What does the planning illustration represent?
The study-design information describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers effects expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, sample-size outputs are expressed as participants per arm for 80% or 90% power; time-to-event outputs are expressed as total events. These are planning illustrations, not observed power and not evidence that the original trial was designed with those assumptions.
The planning setup does not turn this non-randomized study into a controlled comparison. Any illustration that assumes equal allocation between two arms remains hypothetical in relation to the actual design. It should not be read as a justification for the enrollment of 6, or as evidence that the study had adequate power to answer a particular question. The sample-size justification for the trial is not reported in the registry record.
Were formal analyses reported?
The registry lists 10 outcome measures and 0 analyses. That does not supply an inferential model, adjustment strategy, handling of repeated measurements, or treatment-effect estimate. The statistical analysis plan, including any interim analyses, is not reported in the registry record. No method should be imputed from the trial phase or outcome list.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures, including the primary safety outcome and secondary measures of bleeding, FIX activity, replacement therapy, immune response, and quality of life. When many outcomes are examined, the chance of at least one apparently unusual result can increase if each is tested separately. General statistical approaches can address multiplicity, but the registry record does not report whether any adjustment was planned or used.
The record lists 0 analyses. It therefore does not provide reported hypothesis tests, adjusted estimates, confidence intervals, or an account of how outcome multiplicity was handled. The statistical analysis plan is not reported in the registry record. No interim analyses or stopping boundaries are described in the registry record, and none should be assumed.
Missing-data handling is also not reported in the registry record. The safety population is defined as all participants who received DTX101, including participants with a partial dose or failed infusion, but that definition does not explain how missing follow-up, incomplete questionnaires, or unavailable laboratory measurements were handled. The actual follow-up completed by each participant is not reported in the registry record.
Different outcomes may have different analysis populations and available observations. The registry record does not report outcome-specific denominators or analysis populations for the secondary outcomes. Consequently, the enrollment count alone should not be treated as the denominator for every listed measure. No imputation method or sensitivity analysis is reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| DTX101, Cohort 1 | 1 | 3 | 33.3% |
| DTX101, Cohort 2 | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| DTX101, Cohort 1 | 0 of 3 |
| DTX101, Cohort 2 | 0 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| DTX101, Cohort 1 | 3 of 3 |
| DTX101, Cohort 2 | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | DTX101, Cohort 1 | DTX101, Cohort 2 |
|---|---|---|---|
| Musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | 1 of 3 | 0 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | DTX101, Cohort 1 | DTX101, Cohort 2 |
|---|---|---|---|
| Investigations | Investigations | 1 of 3 | 3 of 3 |
| Infections and infestations | Infections and infestations | 1 of 3 | 2 of 3 |
| Injury, poisoning and procedural complications | Injury, poisoning and procedural complications | 2 of 3 | 1 of 3 |
| Musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | 2 of 3 | 1 of 3 |
| Gastrointestinal disorders | Gastrointestinal disorders | 1 of 3 | 1 of 3 |
| General disorders and administration site conditions | General disorders | 1 of 3 | 1 of 3 |
| Nervous system disorders | Nervous system disorders | 1 of 3 | 1 of 3 |
| Respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 2 of 3 |
| Eye disorders | Eye disorders | 0 of 3 | 1 of 3 |
| Psychiatric disorders | Psychiatric disorders | 0 of 3 | 1 of 3 |
Serious events with the highest arm-level rate: musculoskeletal and connective tissue disorders (33.3%).
The safety figures list 3 participants at risk in Cohort 1 and 3 in Cohort 2. Serious adverse events were recorded for 1 participant in Cohort 1 and 0 participants in Cohort 2. The count for other adverse events is 3 in each cohort. Deaths are recorded as 0 in both cohorts. These figures are participant counts, not counts of every event experienced.
The listed serious-event term is musculoskeletal and connective tissue disorders, reported at 33.3%. That term is a category label; it does not establish the cause of the event or its relationship to DTX101. The record’s AE definition includes occurrences regardless of causal relationship. Detailed event descriptions and treatment-related judgments are not reported in the registry record.
Follow-up was specified as up to 52 weeks after dosing for Cohort 1 and 44 weeks after dosing for Cohort 2. The phrase “up to” does not mean that every participant was observed for the maximum period. Individual follow-up durations are not reported in the registry record. The small cohort counts and differing follow-up periods limit direct comparisons between cohorts.
12. What the Result Does, and Does Not, Mean
The posted record supports a narrow description of safety observations in this study: it reports participant counts for serious and other adverse events in two small dose cohorts, along with no deaths listed in either cohort. Those counts are tied to the participants who received DTX101 and to the study’s recorded follow-up periods. They do not give a precise estimate of the frequency of events beyond the enrolled participants.
The record does not establish that DTX101 caused or prevented any event. AEs were defined regardless of causal relationship, and the event-specific relationship to treatment is not reported in the registry record. The non-randomized design, lack of a control group, open-label conduct, and small enrollment mean that the safety observations cannot be separated from other possible explanations using these data alone.
The record also does not establish efficacy. Although secondary outcomes include annualized bleeding rate, FIX activity, replacement therapy, immune response, and quality of life, their numerical results are not reported in the registry record. No formal analysis results are listed. The available safety counts cannot substitute for those missing outcome results.
A zero count in a cohort means no event was recorded among the participants listed for that category; it is not proof that the event is impossible or would not occur in a larger group. Similarly, an event observed in a cohort does not by itself show that treatment produced it. These distinctions are especially important when the cohorts are small and not randomized against one another.
The study’s terminated status is recorded, but the reason for termination is not reported in the registry record. The status alone should not be used to infer a safety concern, lack of benefit, or any other cause. The defensible interpretation is limited to the design details and participant counts that are reported.
13. Why This Trial Matters Statistically
This study illustrates why early-phase dose-finding records need to be read primarily as descriptions of enrolled participants rather than as controlled estimates of treatment effects. It enrolled 6 participants and used two non-randomized dose cohorts, with no masking and no control group. Those features constrain what a difference, or lack of difference, between the cohort counts can mean.
It also shows the importance of keeping an outcome’s unit clear. The primary endpoint counts participants with event classifications. It is not the same as a count of all events, an event rate, or a causal estimate. Interpreting the numbers requires attention to the safety population, event definitions, cohort denominators, and specified follow-up periods.
The record makes visible a further distinction between registered outcomes and reported results. Ten outcome measures are listed, but formal analyses are not listed. A broad outcome list does not mean that results for each outcome are available, nor does it reveal the analysis methods used. Missing statistical details should remain unknown rather than being inferred from common practice.
Finally, the planning illustration is not a retrospective measure of how informative the study was. Assumptions used for a planning calculation do not create a randomized comparison or show that an analysis was prespecified. Separating planning illustrations from observed findings helps prevent hypothetical sample-size calculations from being mistaken for trial results.
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 total enrollment was 6, with 3 participants at risk in each dose cohort. Such small groups offer limited precision and make the descriptive counts sensitive to individual observations. The registry record does not report confidence intervals that would quantify uncertainty around the safety figures.
The design was non-randomized, open-label, and single-group, with no control arm. Cohort counts are therefore not a like-for-like comparison, and the posted information cannot isolate a dose effect or distinguish treatment-associated events from events that might have occurred for other reasons. How participants were assigned to the cohorts is not reported in the registry record.
The follow-up windows differed: up to 52 weeks after dosing in Cohort 1 and up to 44 weeks after dosing in Cohort 2. Individual observation times and the handling of incomplete follow-up are not reported in the registry record. The available counts may not represent equal observation time across participants or cohorts.
Results for the listed secondary outcomes are not reported in the registry record, and no formal analyses are listed. The statistical analysis plan, missing-data methods, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record. The reason the study was terminated is also not reported in the registry record. These gaps limit interpretation beyond the descriptive safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Dose Finding Study of DTX101 (AAVrh10FIX) in Adults With Moderate/Severe to Severe Hemophilia B — NCT02618915.
- Registry record last updated 2018-11-14; status last verified 2018-10.
- Results first posted 2018-11-14.
- 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
NCT02618915 is a Phase I/II, open-label, non-randomized dose-finding study of a single DTX101 infusion in adult males with moderate/severe to severe hemophilia B. Enrollment was 6, with Cohort 1 receiving 1.6 x 10^12 GC/kg and Cohort 2 receiving 5.0 x 10^12 GC/kg. The primary outcome counted participants with AEs, TEAEs, and SAEs. Safety follow-up was specified as up to 52 weeks for Cohort 1 and 44 weeks for Cohort 2.
The posted safety counts list 1 participant with a serious adverse event in Cohort 1 and 0 in Cohort 2; other adverse-event counts were 3 in each cohort, and no deaths were listed. The registry lists 10 outcome measures and 0 analyses. Numerical results for the secondary outcomes, detailed analysis methods, and the reason for termination are not reported in the registry record.