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 Study to Evaluate the Effect of XmAb®5871 on Disease Activity in Patients With IgG4-Related Disease (RD) (NCT02725476), a na phase 2 study. The primary outcome is Proportion of Patients With an Improvement in IgG4-RD Activity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02725476 |
| Phase | Phase 2 |
| Condition | IgG4-RD |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Xencor, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with IgG4-related disease (IgG4-RD) who received at least a partial dose of XmAb5871 made up the stated Intent to Treat population. The registry reports enrollment of 20 participants, but does not report how many were included in that population or how many contributed data to the primary outcome.
Intervention
XmAb5871, a biological intervention, was administered by intravenous infusion for up to a total of 12 infusions. The record describes a 5 mg/kg group and a fixed-dose group for adverse-event reporting. It does not state in the primary outcome description how participants were assigned to those dose groups or provide a dose-specific primary outcome result.
Comparator
There was no concurrent control arm. The study was open-label and single-arm, with allocation listed as not applicable and no masking. Consequently, the study does not provide a like-for-like comparison with placebo, standard care, or another treatment.
Primary question
The primary question was how many participants had an improvement in IgG4-RD activity from baseline Day 1 to Day 169. Improvement was defined as a decrease of at least 2 points in the IgG4-RD Responder Index from the Day 1 pre-dose score. The registry does not report the number or proportion meeting that definition, so the primary question cannot be answered from the recorded outcome results.
This design can describe outcomes among participants treated in the study, but without a control group it cannot separate changes occurring during treatment from changes that might have occurred for other reasons. The registry record also does not report a comparative estimate or a statistical test for the primary question.
3. Trial Design
This was a Phase 2, open-label, single-arm pilot study of XmAb5871 in patients with IgG4-RD. The registry lists enrollment of 20 and describes the study as completed. The recorded start was 2016-03, and primary completion was 2017-12. These dates describe the registry record; they do not establish when each participant began or finished treatment.
The intervention was XmAb5871, categorized as a biological intervention. The arm description says it was administered by intravenous infusion for up to a total of 12 infusions. The adverse-event record separates participants into a 5 mg/kg group and a fixed-dose group. The primary outcome record does not provide a dose-specific breakdown or explain how the dose groups were formed. A control arm, random allocation, and masking are not part of the recorded design.
The primary endpoint concerned improvement in disease activity from baseline Day 1 to Day 169. A secondary outcome concerned the number of patients experiencing a treatment-emergent adverse event assessed using CTCAE v4.3. The registry lists two outcome measures but no analyses. It does not report the protocol’s sample-size justification, detailed analysis plan, or whether any interim analyses were planned.
The single-arm structure is central to interpretation. Outcomes can be described for participants who received the intervention, but there is no concurrent comparison to estimate what would have happened under another treatment or without the study intervention. Open-label status also means that masking was not used, according to the registry. These features do not invalidate descriptive reporting, but they constrain conclusions about comparative effects.
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 | XmAb5871 5 mg/kg | XmAb5871 Fixed Dose |
|---|---|---|
| STARTED | 15 | 5 |
| COMPLETED | 12 | 4 |
| NOT COMPLETED | 3 | 1 |
Reasons for not completing this period:
| Reason | XmAb5871 5 mg/kg | XmAb5871 Fixed Dose |
|---|---|---|
| Physician Decision | 2 | 0 |
| Adverse Event | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT) Population: All patients who have received at least a partial dose of XmAb5871.
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 | XmAb5871 5 mg/kg | XmAb5871 Fixed Dose | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 5 | 20 | |
| Age, Continuous | years | 60.1 (SD 10.57) | 51.2 (SD 14.11) | 57.9 (SD 11.82) |
| Sex: Female, Male: Female | Participants | 5 | 1 | 6 |
| Sex: Female, Male: Male | Participants | 10 | 4 | 14 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 15 | 5 | 20 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 2 | 3 |
| Race (NIH/OMB): White | Participants | 12 | 3 | 15 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 15 | 5 | 20 |
| Serum IgG4 level at Baseline | mg/dL | 440.33 (SD 622.990) | 858.60 (SD 351.608) | 544.90 (SD 588.674) |
| Involved Areas at Baseline: Bile Ducts | Participants | 2 | 0 | 2 |
| Involved Areas at Baseline: Constitutional Symptoms | Participants | 6 | 1 | 7 |
| Involved Areas at Baseline: Heart / Pericardium | Participants | 3 | 0 | 3 |
| Involved Areas at Baseline: Kidney | Participants | 5 | 1 | 6 |
| Involved Areas at Baseline: Lacrimal Glands | Participants | 7 | 3 | 10 |
| Involved Areas at Baseline: Lungs | Participants | 4 | 2 | 6 |
| Involved Areas at Baseline: Lymph Nodes | Participants | 10 | 4 | 14 |
| Involved Areas at Baseline: Nasal Cavity Lesion | Participants | 3 | 0 | 3 |
| Involved Areas at Baseline: Orbital Lesion | Participants | 2 | 1 | 3 |
| Involved Areas at Baseline: Other | Participants | 4 | 4 | 8 |
| Baseline IgG4-RD Responder Index Total Activity Score | Total Activity Score | 11.5 (SD 6.65) | 12.8 (SD 6.42) | 11.8 (SD 6.45) |
6. Primary Endpoint
The registry lists the primary outcome as Proportion of Patients With an Improvement in IgG4-RD Activity, measured over Baseline Day 1 to Day 169.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with an improvement in IgG4-RD activity over the period from baseline Day 1 to Day 169. Improvement was defined as a decrease of at least 2 points from the Day 1 pre-dose score on the IgG4-RD Responder Index. The registry identifies the unit as participants and the measure as a count. Although the title describes a proportion, the record does not provide the count or proportion of participants who met the definition.
The index’s total activity score ranges from 0 to a maximum of 162. Higher scores represent greater, or worse, disease activity; a score of 0 represents no activity other than residual fibrosis. In general, a threshold-based response endpoint turns a change on a scale into a classification: a participant either meets the stated improvement criterion or does not. Such an endpoint can make a clinical definition easier to interpret, while discarding information about the size of changes beyond the threshold.
Here, the registry’s stated threshold establishes what was intended to count as improvement. It does not report baseline or follow-up score distributions, individual changes, the number meeting the threshold, or uncertainty around an estimated response proportion. Without those results, the endpoint definition can be described, but the observed response cannot be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a primary outcome but does not report its observed result. In particular, it gives no count of participants whose Responder Index decreased by at least 2 points, no proportion meeting that criterion, and no confidence interval or test result. The stated enrollment of 20 does not substitute for an outcome denominator: the registry defines the Intent to Treat population as patients who received at least a partial dose, but does not state how many participants were in that population or contributed primary endpoint data. Therefore, no estimate of the primary response rate or its precision can be drawn from the posted results.
The study was open-label and single-arm. Its results, if reported, would describe outcomes among treated participants, rather than a contrast between treatment groups. Without a concurrent control, an observed change from baseline could not by itself establish how much of the change was attributable to the intervention rather than other influences. This is a design limitation, not a statistical adjustment that can be resolved from the information in the registry record.
The safety data include separate counts for the 5 mg/kg and fixed-dose groups. For the serious-event category, the record lists 1 affected participant among 15 at risk in the 5 mg/kg group and 1 among 5 at risk in the fixed-dose group. For the other adverse-event category, it lists 7 among 15 and 3 among 5, respectively. Deaths are listed as 0 in each group. These are descriptive counts; the record does not report a comparative safety analysis, uncertainty intervals, or a causal assessment. The group sizes are not evidence of randomized or otherwise comparable treatment assignment.
The registry also lists chronic inflammatory demyelinating polyradiculoneuropathy and chronic lymphocytic leukaemia at 20.0% each among the top serious terms, and pneumonia at 6.7%. Those entries should be read as listed event-term percentages, not as comparative estimates. The record does not clarify in the available outcome information the participant-level counting rules behind these terms.
A planning illustration is described using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects set as stated fractions of the observed effect. It is not the trial’s own design, and it does not turn this single-arm study into a randomized comparison. No observed primary effect is reported in the registry record, so no trial-specific observed effect can be interpreted from that description. Planning sample sizes are not observed power and do not supply missing outcome evidence.
9. Statistical Methods Explained
The registry identifies the primary measure as a count of participants, while the outcome title refers to a proportion. These describe related but distinct ways of presenting a binary endpoint. A count states how many participants met a definition; a proportion relates that count to the number assessed. For the endpoint here, the classification is whether a participant had a decrease of at least 2 points on the IgG4-RD Responder Index from the Day 1 pre-dose score by Day 169. The record reports neither the qualifying count nor the denominator for that analysis, so neither a response count nor an observed proportion can be stated.
In general, a confidence interval expresses the uncertainty around an estimated quantity. For a response proportion, it would help readers judge how precisely the observed response rate is estimated. A narrow interval generally indicates greater precision than a wide interval, though precision is not the same as freedom from bias. No confidence interval for the primary response is reported in the registry record. Because the response estimate itself is absent, its precision cannot be evaluated.
The study’s single-arm design matters to the interpretation of any change from baseline. In a controlled study, a comparison can help distinguish the outcome under one assigned condition from the outcome under another. In a single-arm study, the observed outcome has no concurrent control outcome against which to estimate a treatment contrast. Comparing participants with their own baseline can describe change, but it does not on its own identify the cause of that change. This is a general design principle and does not presume what the unreported trial result would have been.
Open-label means masking was not used, as recorded for this study. In general, knowledge of treatment assignment can influence participant reports, clinical assessments, or decisions about care and follow-up, depending on the endpoint and study procedures. The registry does not report procedures intended to address such influences. It also does not report assessor masking, a blinded endpoint review, or other details that would establish how the primary score was evaluated.
The Responder Index is a bounded activity score, ranging from 0 to a maximum of 162, with higher scores indicating worse activity. The primary endpoint applies a threshold to change in that score rather than reporting the full distribution of score changes. In general, thresholding can make a response criterion straightforward to communicate, but participants with different magnitudes of change may be placed in the same response category. The registry does not report group summaries or participant-level changes that would allow readers to examine the score as a continuous measure alongside the threshold endpoint.
The sample-size planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It says that the planning illustration is computed from the observed effect rather than from the trial’s own design. The registry does not report the trial’s sample-size justification, and the primary observed effect is not reported. Therefore, the planning assumptions should not be read as evidence that the study was designed around those assumptions or that it had a particular probability of detecting an effect. Sample-size calculations are planning illustrations, not observed power.
For general interpretation, over-dispersion is relevant when count outcomes vary more than a statistical model assumes; failing to account for it can make uncertainty estimates too optimistic. That issue cannot be evaluated for the primary endpoint from the registry information: the endpoint is recorded as a participant count, but no analysis model, distributional assessment, or dispersion estimate is reported. No conclusion should be drawn that over-dispersion was present or that a model addressing it was used.
The registry lists zero analyses. It does not report a primary hypothesis test, an effect estimate, a confidence interval, covariate adjustment, or a model specification. The absence of a reported analysis is distinct from a result that is statistically non-significant: no p-value is available to interpret. Likewise, no multiplicity procedure or hierarchy among outcomes is reported. Those details should not be inferred from the fact that the record lists a primary and a secondary outcome.
The adverse-event counts are descriptive. In general, adverse-event counts can be summarized by participants affected, events recorded, severity, seriousness, or relationship to treatment; these are not interchangeable quantities. The registry’s labels identify affected participants and participants at risk for its two dose-group entries, but the record does not report a comparative model or uncertainty estimates. The event-term percentages are also reported without a statistical comparison. They should not be treated as proof of a difference between groups.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary disease-activity outcome and a secondary treatment-emergent adverse-event outcome assessed by CTCAE v4.3. It does not report a testing hierarchy, multiplicity adjustment, or other procedure for controlling the risk of false-positive findings across outcomes or analyses. Because the registry lists zero analyses, it also provides no outcome-specific p-values or statistical conclusions that would show how multiple testing was handled. The absence of a reported procedure does not establish that none was used outside the registry record.
The primary outcome description defines an Intent to Treat population as all patients who received at least a partial dose of XmAb5871. The registry does not report how many participants met that definition, how many had primary endpoint data, or how missing Day 169 measurements were handled. It does not describe imputation, exclusion rules, sensitivity analyses, or reasons for missing data. Consequently, the denominator and the potential influence of missing observations on the primary result cannot be assessed.
The record lists enrollment of 20, but enrollment alone does not establish the number analyzed for any outcome. It also does not report whether every enrolled participant received treatment, completed follow-up, or contributed to each safety summary. These are distinct population questions, and the registry does not provide the flow details needed to answer them.
No interim analyses, stopping rules, or detailed statistical analysis plan are reported in the registry record. These omissions limit assessment of how outcomes were selected and analyzed, but they do not show what procedures may have been specified elsewhere. The posted information supports describing the endpoint definitions and the recorded adverse-event counts; it does not support reconstructing an unreported analysis plan.
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 |
|---|---|---|---|
| XmAb5871 5 mg/kg | 1 | 15 | 6.7% |
| XmAb5871 Fixed Dose | 1 | 5 | 20.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| XmAb5871 5 mg/kg | 0 of 15 |
| XmAb5871 Fixed Dose | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| XmAb5871 5 mg/kg | 7 of 15 |
| XmAb5871 Fixed Dose | 3 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | XmAb5871 5 mg/kg | XmAb5871 Fixed Dose |
|---|---|---|---|
| Pneumonia | Infections and infestations | 1 of 15 | 0 of 5 |
| Chronic inflammatory demyelinating polyradiculoneuropathy | Nervous system disorders | 0 of 15 | 1 of 5 |
| Chronic lymphocytic leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 15 | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | XmAb5871 5 mg/kg | XmAb5871 Fixed Dose |
|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 3 of 15 | 1 of 5 |
| Nausea | Gastrointestinal disorders | 2 of 15 | 2 of 5 |
| Vomiting | Gastrointestinal disorders | 1 of 15 | 2 of 5 |
| Diarrhoea | Gastrointestinal disorders | 2 of 15 | 0 of 5 |
| Chills | General disorders | 2 of 15 | 0 of 5 |
| Headache | Nervous system disorders | 2 of 15 | 0 of 5 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 1 of 5 |
| Upper respiratory tract infection | Infections and infestations | 0 of 15 | 2 of 5 |
Serious events with the highest arm-level rate: chronic inflammatory demyelinating polyradiculoneuropathy (20.0%), chronic lymphocytic leukaemia (20.0%), pneumonia (6.7%).
The registry lists adverse-event information separately for XmAb5871 5 mg/kg and XmAb5871 Fixed Dose. In the serious-event category, 1 participant is listed as affected among 15 at risk in the 5 mg/kg group; in the fixed-dose group, 1 is listed among 5 at risk. In the other adverse-event category, the corresponding entries are 7 among 15 and 3 among 5. Deaths are listed as 0 for both groups.
These are descriptive entries, not evidence of a treatment-group difference. The record does not say that the dose groups were randomized or comparable, and it reports no confidence intervals or formal comparison. The labels also distinguish affected participants from events, which should not be conflated: the counts given are participants affected, not necessarily the total number of event episodes.
The registry lists chronic inflammatory demyelinating polyradiculoneuropathy and chronic lymphocytic leukaemia as top serious terms at 20.0% each, and pneumonia at 6.7%. The record does not provide enough detail to interpret these percentages as comparative risks, determine their relation to a particular dose group, or assess causality. They should be read as reported safety summaries, not as proof that XmAb5871 caused an event or that one dose group had greater risk.
12. What the Result Does, and Does Not, Mean
The registry record establishes the intended clinical question and the outcome definitions for this completed pilot study. It does not report the primary endpoint result. There is no stated count or proportion of participants with the defined decrease in IgG4-RD Responder Index, and no confidence interval or statistical test. Thus, the record does not establish the observed frequency or precision of improvement according to the endpoint definition.
The study’s single-arm design is also important: it has no concurrent control group. Even if a before-and-after change had been reported, that change alone would describe what happened among treated participants, not determine what would have happened without treatment or under another treatment. The open-label design and absence of reported masking procedures further constrain interpretation of assessed outcomes. These considerations define what the design can support; they do not predict what the missing result would show.
The safety entries describe participants affected in two dose groups and list zero deaths in each. They are not a randomized comparison, and no statistical comparison or uncertainty interval is reported. The listed serious-event terms and percentages provide additional descriptive information but do not establish causation or a comparative risk.
The most defensible reading is therefore limited: this was a completed Phase 2 single-arm study with a specified disease-activity response definition and recorded safety summaries, but the registry’s posted results do not include the primary response result or its statistical analysis. No claim about the intervention’s effectiveness, lack of effectiveness, or comparative safety follows from the missing primary result. A planning illustration cannot fill that gap; planning calculations concern hypothetical study design, not observed participant outcomes.
13. Why This Trial Matters Statistically
This study illustrates why a clear endpoint definition and a reported endpoint result are both necessary for statistical interpretation. The record defines improvement using a decrease of at least 2 points on the IgG4-RD Responder Index from a specified baseline score. That definition tells readers what would count as a response, but without the response count and denominator it does not reveal how often the criterion was met.
It also illustrates the distinction between a within-group description and a controlled treatment comparison. The open-label, single-arm design can organize observations from participants receiving XmAb5871, but it lacks a concurrent control for estimating a contrast. This distinction is especially useful when reading pilot studies: a study can establish a measurement framework and report descriptive outcomes without providing a causal comparative estimate.
The registry’s adverse-event entries demonstrate a similar issue. Counts by dose group can be read as descriptive records, but group labels alone do not establish comparability. Without information on assignment, a statistical comparison, or uncertainty estimates, the entries should not be treated as evidence that one dose has a different safety profile.
Finally, the stated planning assumptions should be kept separate from the trial’s actual design and observed data. A hypothetical two-arm planning illustration is not evidence that this single-arm trial used that design, and it cannot substitute for a reported response estimate. The record therefore provides a useful example of how design, endpoint definition, analysis reporting, and uncertainty each contribute different pieces of evidence.
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 primary limitation for interpretation is that the registry does not report the primary outcome result or any analysis. Although the endpoint is defined, the count meeting the response threshold, its denominator, and its precision are absent. The listed enrollment of 20 cannot be treated as the primary analysis population because the record does not report the number who received at least a partial dose or had endpoint data.
The design was open-label and single-arm, with no control group. It therefore cannot provide a concurrent treatment comparison, and the record does not report a method that would address the lack of a control. The registry also does not report dose assignment procedures, so the adverse-event entries for the 5 mg/kg and fixed-dose groups cannot be interpreted as like-for-like comparisons.
Further details needed to evaluate the primary result are not reported in the registry record: missing-data handling, participant flow, score distributions, statistical models, confidence intervals, hypothesis tests, and analysis populations beyond the stated ITT definition. The record also does not report assessor masking or a detailed analysis plan. No conclusion about procedures outside the registry should be inferred from these omissions.
Safety interpretation is limited by the absence of comparative analyses and uncertainty estimates, as well as by the limited context for the listed serious-event terms. The registry lists affected participants and deaths by dose group, but does not provide a causal assessment. These limitations are specific to what is recorded and do not establish that unreported events, procedures, or analyses did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate the Effect of XmAb®5871 on Disease Activity in Patients With IgG4-Related Disease (RD) — NCT02725476.
- Registry record last updated 2018-12-07; status last verified 2018-12.
- Results first posted 2018-12-07.
- 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.
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18. Record Summary
NCT02725476 is a completed, open-label, single-arm Phase 2 pilot study of XmAb5871 in IgG4-RD. The registry lists enrollment of 20, a start of 2016-03, and primary completion in 2017-12. XmAb5871 was administered by intravenous infusion for up to a total of 12 infusions.
The primary endpoint was the number of participants with a decrease of at least 2 points on the IgG4-RD Responder Index from the Day 1 pre-dose score, assessed from baseline Day 1 to Day 169. The registry does not report the endpoint result or an analysis. Safety entries list affected participants by dose group, zero deaths in both groups, and several top serious-event terms. These entries are descriptive and do not provide a controlled comparison.