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 ALXN1210 Versus Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab (NCT03056040), a na phase 3 study. The primary outcome is Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03056040 |
| Phase | Phase 3 |
| Condition | Paroxysmal Nocturnal Hemoglobinuria (PNH) |
| Allocation | Not applicable (single group) |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 202 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alexion Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable after treatment with eculizumab for at least 6 months. The primary analysis population is described as the Full Analysis Set: participants who received at least 1 dose of randomized treatment.
Intervention
Ravulizumab, given using weight-based doses during the 26-week Primary Evaluation Period. The registry describes an initial dose on Day 1 and subsequent doses on Days 15, 71, and 127.
Comparator
Eculizumab, given at 900 mg every 2 weeks during the 26-week Primary Evaluation Period.
Primary question
The study aimed to assess whether ravulizumab was noninferior to eculizumab for percent change in lactate dehydrogenase (LDH) from baseline to Day 183. The noninferiority margin and the primary endpoint estimates are not reported in the registry record.
LDH is described as an indicator of intravascular hemolysis in PNH. The endpoint therefore focuses on a laboratory measure related to hemolysis, rather than on symptoms, transfusions, or other clinical events. A decrease in LDH indicates a reduction in hemolysis according to the registry description.
The comparison is framed around adults already receiving eculizumab and clinically stable after at least 6 months of treatment. It does not directly address people new to treatment or those outside this described population. Secondary outcomes include breakthrough hemolysis, FACIT-Fatigue score change, transfusion avoidance, and hemoglobin stabilization. These are listed for Day 183 and, in some cases, through the end of the study. Their outcome estimates are not reported in the registry record.
The record identifies the study as randomized in its official title, but its allocation field is NA and the record flags the arms as not a like-for-like control comparison. That qualification limits how confidently the arm contrast can be interpreted as a randomized causal comparison from the registry information alone.
3. Trial Design
This was a Phase 3, open-label, active-controlled, parallel study of ravulizumab and eculizumab in adults with PNH who were clinically stable after receiving eculizumab for at least 6 months. The record reports enrollment of 202. It lists the study as completed, with a start date of 2017-05-17 and primary completion on 2022-02-21.
The primary evaluation period lasted 26 weeks. During this period, participants assigned to ravulizumab received a weight-based dose ranging from 2400 to 3000 milligrams (mg) on Day 1, followed by weight-based doses ranging from 3000 to 3600 mg on Days 15, 71, and 127. Participants assigned to eculizumab received 900 mg every 2 weeks. The registry describes an opportunity to enter an extension period after the primary evaluation period. In that period, participants in both groups could receive weight-based ravulizumab for up to 4 years.
The study was open-label, meaning masking was listed as none. Knowledge of treatment assignment can affect participant experience, reporting, and some assessments; the extent of any such influence is not reported in the registry record. The primary endpoint is a laboratory measure, but the record does not specify procedures used to limit assessment or analysis bias.
The official title describes a randomized study, but the allocation field is NA. The registry also flags the arms as not a like-for-like control comparison. Thus, although the design is described as parallel and the treatments are named as active comparators, the registry record does not establish the allocation details needed to interpret the contrast as a conventional randomized comparison. Further details of the allocation process are not reported in the registry record.
The intervention descriptions provide dosing information for the primary period and describe the extension, but they do not establish adherence, treatment discontinuation, or exposure for each participant. Those details are not reported in the registry record. Similarly, eligibility criteria beyond the stated clinical stability and prior eculizumab treatment 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: Participants were stratified into 1 of 2 groups based on their transfusion history. Stratified participants were randomly assigned in a 1:1 ratio to receive ravulizumab or eculizumab.
Primary Evaluation Period
| Stage | Ravulizumab/Ravulizumab | Eculizumab/Ravulizumab |
|---|---|---|
| STARTED | 98 | 99 |
| Received at Least 1 Dose of Study Drug | 97 | 98 |
| Participants in the Full Analysis Set (FAS) | 97 | 98 |
| COMPLETED | 96 | 95 |
| NOT COMPLETED | 2 | 4 |
Reasons for not completing this period:
| Reason | Ravulizumab/Ravulizumab | Eculizumab/Ravulizumab |
|---|---|---|
| Withdrawal by Subject | 1 | 1 |
| Lack of Efficacy | 0 | 1 |
| Pregnancy | 0 | 1 |
| Randomized, not treated | 1 | 1 |
Extension Period
| Stage | Ravulizumab/Ravulizumab | Eculizumab/Ravulizumab |
|---|---|---|
| STARTED | 96 | 95 |
| COMPLETED | 92 | 88 |
| NOT COMPLETED | 4 | 7 |
Reasons for not completing this period:
| Reason | Ravulizumab/Ravulizumab | Eculizumab/Ravulizumab |
|---|---|---|
| Physician Decision | 3 | 3 |
| Lost to Follow-up | 0 | 1 |
| Death | 0 | 3 |
| Withdrawal by Subject | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab).
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.
Population: All participants who received at least 1 dose of study treatment (ravulizumab or eculizumab).
| Characteristic | Unit | Ravulizumab/Ravulizumab | Eculizumab/Ravulizumab | Total |
|---|---|---|---|---|
| Participants analysed | 97 | 98 | 195 | |
| Age, Continuous | years | 46.6 (SD 14.41) | 48.8 (SD 13.97) | 47.7 (SD 14.19) |
| Sex: Female, Male: Female | Participants | 47 | 50 | 97 |
| Sex: Female, Male: Male | Participants | 50 | 48 | 98 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 | 4 | 7 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 76 | 77 | 153 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 18 | 17 | 35 |
| Race/Ethnicity, Customized: White | participants | 50 | 61 | 111 |
| Race/Ethnicity, Customized: Asian | participants | 23 | 19 | 42 |
| Race/Ethnicity, Customized: Not Reported | participants | 13 | 13 | 26 |
| Race/Ethnicity, Customized: Black or African American | participants | 5 | 3 | 8 |
| Race/Ethnicity, Customized: Unknown | participants | 3 | 1 | 4 |
| Race/Ethnicity, Customized: Other | participants | 2 | 1 | 3 |
| Race/Ethnicity, Customized: Multiple | participants | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183, measured over Baseline, Day 183.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percent change |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is percent change in lactate dehydrogenase (LDH) from baseline to Day 183. LDH is an indicator of intravascular hemolysis in participants with PNH. The registry describes a decrease in LDH as indicating a reduction in hemolysis. The endpoint therefore uses a laboratory measure to assess change in a biological process relevant to the condition.
Baseline was defined as the average of all available on-study assessments before the first study drug infusion. The outcome was analyzed as a continuous measure, with a least-squares mean and a 95% confidence interval specified as the summary. Least-squares means are model-based estimates that account for terms included in the analysis model; they are not simply raw group averages. The confidence interval describes uncertainty around an estimate under the model and its assumptions.
The model included treatment, study visit, and the interaction between study visit and treatment as fixed categorical effects. It also included baseline LDH as a continuous fixed covariate and the stratification randomization indicator for packed red blood cell transfusion history within 12 months before Day 1. The registry does not report the numerical least-squares means, confidence intervals, or treatment contrast for the primary outcome. It also does not report the noninferiority margin, so the intended decision threshold cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a noninferiority objective: assessing ravulizumab against eculizumab for percent change in LDH from baseline to Day 183. However, the primary endpoint estimates and the noninferiority margin are not reported in the registry record. Without the estimated treatment contrast, its confidence interval, and the prespecified margin, the noninferiority conclusion cannot be independently assessed from this record.
The endpoint is a model-based continuous outcome. Its interpretation would depend on the estimated change in each treatment group and, especially for noninferiority, the uncertainty around the difference between groups relative to the specified margin. A confidence interval that is compatible with several effects can leave substantial uncertainty even when a point estimate appears favorable. The registry record does not provide the values needed to describe the magnitude or precision of the primary comparison.
The analysis description identifies adjustments for baseline LDH, study visit, treatment, their visit-by-treatment relationship, and transfusion history used as a stratification indicator. These model terms are relevant to interpreting the estimate, but do not by themselves establish that the comparison was unbiased or that the model fit the observed data. Diagnostics and details of model implementation are not reported in the registry record.
The allocation field is NA, and the registry flags the arms as not a like-for-like control comparison, despite the official title describing randomization. This discrepancy matters: the interpretation of a treatment contrast depends on how participants entered the arms and whether prognostic factors were balanced. The allocation process and any adjustment for imbalances beyond the listed model terms are not reported in the registry record. The contrast should therefore not be treated as a confirmed randomized causal estimate on the basis of the record alone.
The secondary outcomes broaden the clinical and patient-reported perspective. They include breakthrough hemolysis, FACIT-Fatigue score change, transfusion avoidance, and stabilized hemoglobin, with some outcomes assessed through Day 183 and others also through the end of the study. Their estimates are not reported in the registry record. Their listing does not establish that they support, contradict, or explain the primary outcome.
The extension is described as lasting up to 4 years, but the record does not provide outcome estimates that would establish the direction or durability of changes over that period. Extension treatment also differs from the original comparison: participants in the eculizumab group could switch to ravulizumab. Consequently, an extension-period contrast would not be equivalent to the primary-period comparison between the initially named treatments. The registry reports some safety counts by period and treatment sequence, but these are not a substitute for the missing efficacy estimates.
9. Statistical Methods Explained
What does a least-squares mean represent?
A least-squares mean is an estimate from a statistical model, adjusted for the other model terms. In this study, the primary endpoint was a continuous measure: percent change in LDH. The specified model included treatment, study visit, and the interaction of visit with treatment, along with baseline LDH and the transfusion-history stratification indicator. In general, model-based estimates can be useful when outcomes are assessed repeatedly or when baseline values and other planned factors need to be represented in the analysis. Their meaning remains conditional on the model specification and assumptions.
The registry does not report the least-squares mean estimates or the treatment contrast. It is therefore not possible to describe the observed direction, size, or precision of the primary result from the registry record. Nor can a reader determine whether model-adjusted estimates differ materially from unadjusted changes.
Why use a repeated-measures model?
The primary analysis is described as a mixed-effect model for repeated measures (MMRM). In general, repeated-measures methods can account for the fact that observations from the same participant over time are related, rather than treating each visit as independent. The model can estimate treatment patterns over visits and use the specified visit-by-treatment interaction to represent whether the modeled pattern varies by treatment group.
The record names the model and its fixed effects, but does not report the covariance structure, estimation method, degrees-of-freedom approach, or diagnostic checks. These details can matter to the estimated uncertainty and to whether the model adequately represents repeated observations. They are not reported in the registry record.
What does the confidence interval add?
A confidence interval describes the statistical uncertainty around an estimate under the model and its assumptions. A narrow interval indicates greater precision than a wide interval, while an interval spanning a range of materially different effects leaves more uncertainty about the effect size. For a noninferiority assessment, the interval for the treatment contrast is interpreted in relation to a prespecified margin. The registry record does not report either the primary interval or that margin, so the noninferiority assessment cannot be reconstructed.
The record specifies a 95% confidence interval for the primary endpoint summary. That specification identifies the intended uncertainty measure, not the result itself. It does not show whether the interval was narrow, whether it included no difference, or whether it lay within a noninferiority boundary.
What is the role of baseline adjustment?
Baseline LDH was included as a continuous fixed covariate. In general, adjusting for a baseline measure can account for differences in starting values and can improve precision when baseline is associated with the follow-up outcome. The registry defines baseline as the average of all available on-study assessments before the first study drug infusion. It does not report the distribution of baseline LDH, the extent of missing baseline measurements, or the impact of adjustment on the estimates.
The model also included a stratification randomization indicator for packed red blood cell transfusion history within 12 months before Day 1. The field name refers to a randomization indicator, but the allocation field is NA and the record cautions that the arms are not a like-for-like control comparison. How this indicator was used in the analysis, and whether the allocation procedure actually used it, is not fully described in the registry record.
How should noninferiority be assessed?
In general, a noninferiority analysis asks whether the estimated difference is sufficiently compatible with a prespecified boundary, rather than asking only whether the groups differ statistically. The margin must be defined before interpreting the result, and the direction of the contrast must be clear. The treatment estimate and its confidence interval are then evaluated against that margin. The margin, contrast direction, and numerical primary results are not reported in the registry record. Therefore, the stated study objective cannot be judged from the available efficacy information.
Noninferiority conclusions also depend on the integrity of the comparison and the handling of missing observations and treatment changes. The record identifies a Full Analysis Set of participants who received at least 1 dose of randomized treatment, but does not report the number analyzed or the missing-data methods. Additional analysis populations and sensitivity analyses are not reported in the registry record.
What can the safety counts show?
Safety results are reported for the primary evaluation period and extension period, including serious adverse events and other adverse events. In general, counts with denominators give descriptive information about events recorded during a defined period. They do not by themselves establish that a treatment caused an event or that groups had comparable exposure time. Interpretation depends on definitions, observation time, event ascertainment, and participant flow, details that are not fully reported in the registry record.
The extension includes different treatment sequences, including eculizumab followed by ravulizumab. This means extension-period counts describe experience under those sequences and should not be read as a continuation of the original direct comparison. The posted safety counts are descriptive; the registry does not report a comparative statistical analysis of these events.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 9 outcome measures and 5 analyses. It identifies a primary outcome and multiple secondary outcomes, including breakthrough hemolysis, FACIT-Fatigue, transfusion avoidance, and stabilized hemoglobin. When multiple outcomes or analyses are examined, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can control or describe this issue, but the registry does not report whether any adjustment, hierarchical testing procedure, or prespecified interpretation strategy was used. The statistical plan for multiplicity is not reported in the registry record.
The primary population is called the Full Analysis Set and is defined as all participants who received at least 1 dose of randomized treatment. The record does not give the number included in the primary analysis, the number with endpoint data at each visit, or how many participants discontinued or deviated from treatment. It does not report whether a separate per-protocol population was used, which can be relevant to interpreting noninferiority analyses.
Missing-data handling is not reported in the registry record. The MMRM approach is named, but the record does not state the assumptions made about missing observations, how withdrawals or treatment changes were handled, or whether sensitivity analyses tested alternative assumptions. In general, repeated-measures models can use available observations under specified assumptions; they do not eliminate the need to examine why data are missing or how departures from assumptions could affect conclusions.
The record describes an extension after the 26-week Primary Evaluation Period, with ravulizumab used in both treatment sequences. How participants entered or remained in the extension, and how extension data were incorporated into analyses, is not reported in the registry record. This limits interpretation of long-term outcomes and of analyses spanning the primary and extension periods.
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 |
|---|---|---|---|
| Primary Evaluation Period (26 Weeks) Ravulizumab Treatment | 4 | 97 | 4.1% |
| Primary Evaluation Period (26 Weeks) Eculizumab Treatment | 8 | 98 | 8.2% |
| Extension Period (Ravulizumab To Ravulizumab) | 26 | 96 | 27.1% |
| Extension Period (Eculizumab to Ravulizumab) | 33 | 95 | 34.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Primary Evaluation Period (26 Weeks) Ravulizumab Treatment | 0 of 97 |
| Primary Evaluation Period (26 Weeks) Eculizumab Treatment | 0 of 98 |
| Extension Period (Ravulizumab To Ravulizumab) | 0 of 96 |
| Extension Period (Eculizumab to Ravulizumab) | 3 of 95 |
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 |
|---|---|
| Primary Evaluation Period (26 Weeks) Ravulizumab Treatment | 72 of 97 |
| Primary Evaluation Period (26 Weeks) Eculizumab Treatment | 85 of 98 |
| Extension Period (Ravulizumab To Ravulizumab) | 83 of 96 |
| Extension Period (Eculizumab to Ravulizumab) | 85 of 95 |
Most frequent serious adverse event terms
| Event term | Organ system | Primary Evaluation Period (26 Weeks) Ravulizumab Treatment | Primary Evaluation Period (26 Weeks) Eculizumab Treatment | Extension Period (Ravulizumab To Ravulizumab) | Extension Period (Eculizumab to Ravulizumab) |
|---|---|---|---|---|---|
| Pyrexia | General disorders | 0 of 97 | 3 of 98 | 5 of 96 | 0 of 95 |
| Haemolysis | Blood and lymphatic system disorders | 0 of 97 | 2 of 98 | 1 of 96 | 4 of 95 |
| Influenza | Infections and infestations | 1 of 97 | 0 of 98 | 1 of 96 | 3 of 95 |
| Lower respiratory tract infection | Infections and infestations | 1 of 97 | 0 of 98 | 1 of 96 | 1 of 95 |
| Haemolytic anaemia | Blood and lymphatic system disorders | 0 of 97 | 0 of 98 | 2 of 96 | 1 of 95 |
| Colitis | Gastrointestinal disorders | 1 of 97 | 0 of 98 | 1 of 96 | 0 of 95 |
| Cholelithiasis | Hepatobiliary disorders | 0 of 97 | 1 of 98 | 0 of 96 | 1 of 95 |
| Bile duct stone | Hepatobiliary disorders | 0 of 97 | 0 of 98 | 1 of 96 | 1 of 95 |
| COVID-19 | Infections and infestations | 0 of 97 | 0 of 98 | 1 of 96 | 1 of 95 |
| Infection | Infections and infestations | 0 of 97 | 0 of 98 | 0 of 96 | 2 of 95 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Primary Evaluation Period (26 Weeks) Ravulizumab Treatment | Primary Evaluation Period (26 Weeks) Eculizumab Treatment | Extension Period (Ravulizumab To Ravulizumab) | Extension Period (Eculizumab to Ravulizumab) |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 20 of 97 | 20 of 98 | 27 of 96 | 21 of 95 |
| Headache | Nervous system disorders | 27 of 97 | 17 of 98 | 21 of 96 | 21 of 95 |
| Upper respiratory tract infection | Infections and infestations | 19 of 97 | 10 of 98 | 24 of 96 | 19 of 95 |
| Fatigue | General disorders | 7 of 97 | 6 of 98 | 18 of 96 | 19 of 95 |
| Nausea | Gastrointestinal disorders | 8 of 97 | 9 of 98 | 13 of 96 | 16 of 95 |
| Diarrhoea | Gastrointestinal disorders | 9 of 97 | 7 of 98 | 15 of 96 | 14 of 95 |
| Cough | Respiratory, thoracic and mediastinal disorders | 5 of 97 | 10 of 98 | 16 of 96 | 12 of 95 |
| Pyrexia | General disorders | 9 of 97 | 2 of 98 | 15 of 96 | 16 of 95 |
| Abdominal pain | Gastrointestinal disorders | 7 of 97 | 9 of 98 | 12 of 96 | 11 of 95 |
| Dizziness | Nervous system disorders | 3 of 97 | 7 of 98 | 8 of 96 | 15 of 95 |
Serious events with the highest arm-level rate: pyrexia (5.2%), haemolysis (4.2%), influenza (3.2%), infection (2.1%), haemolytic anaemia (2.1%).
During the 26-week Primary Evaluation Period, the registry reports serious adverse events in 4 participants in the ravulizumab group, with 97 at risk, and in 8 participants in the eculizumab group, with 98 at risk. Other adverse events were reported in 72 participants in the ravulizumab group and 85 participants in the eculizumab group. No deaths were reported in either group during this period.
For the Extension Period, the record reports 26 serious adverse events among 96 at risk in the ravulizumab-to-ravulizumab sequence, and 33 among 95 at risk in the eculizumab-to-ravulizumab sequence. Other adverse events were reported in 83 and 85 participants, respectively. The record reports no deaths in the ravulizumab-to-ravulizumab sequence and 3 in the eculizumab-to-ravulizumab sequence.
These are descriptive counts for different periods and treatment sequences, not adjusted comparisons. The extension sequences do not preserve the initial treatment contrast because the eculizumab group switched to ravulizumab. Serious adverse event terms listed as occurring most often include Pyrexia (5.2%), Haemolysis (4.2%), Influenza (3.2%), Infection (2.1%), Haemolytic anaemia (2.1%), and Cholelithiasis (1.1%). Event definitions, exposure-adjusted rates, and comparative safety analyses are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record describes a Phase 3 study designed to assess noninferiority of ravulizumab relative to eculizumab in adults with PNH who were clinically stable after at least 6 months of eculizumab treatment. Its primary endpoint was percent change in LDH from baseline to Day 183, analyzed using a repeated-measures model. The outcome is a laboratory indicator related to intravascular hemolysis, and the registry states that a decrease indicates reduced hemolysis.
The record does not report the primary endpoint estimates, their confidence interval, or the noninferiority margin. It therefore does not establish from the available information whether the result met the study’s stated noninferiority objective, how large the estimated difference was, or how precisely it was estimated. The absence of those values is not evidence for either treatment being better or worse.
Secondary outcomes address breakthrough hemolysis, fatigue, transfusion avoidance, and hemoglobin stabilization. Their estimates are also not reported in the registry record. The safety counts provide descriptive information for the primary and extension periods, but do not establish comparative risks or causal attribution. The extension period includes a switch to ravulizumab for participants initially receiving eculizumab, so it represents treatment sequences rather than a sustained comparison of the original arms.
The record’s official title describes randomization, while its allocation field is NA and it flags the arms as not a like-for-like control comparison. Without allocation details, analysis estimates, and information about missing data and participant flow, the strength of causal interpretation cannot be established from this record. The study description identifies what was intended to be assessed, but the posted information does not permit a conclusion about the primary efficacy result.
13. Why This Trial Matters Statistically
This study raises several important statistical questions for clinical research. First, its stated objective is noninferiority, which requires more than a comparison of point estimates. Interpretation depends on a prespecified margin, an estimate of the treatment contrast, and a confidence interval that can be evaluated against that margin. None of those numerical primary-result details is reported in the registry record, so the objective cannot be assessed from the posted results.
Second, the record illustrates why design fields and descriptions need to be read together. The official title calls the study randomized, but allocation is listed as NA and the registry cautions that the arms are not a like-for-like control comparison. Understanding how participants were assigned is central to deciding whether observed differences can be interpreted causally. The allocation process is not reported in the registry record.
Third, a model description is not a substitute for the fitted result. Naming an MMRM and listing baseline adjustment and other effects clarifies the planned analytical structure, but readers also need estimates, uncertainty intervals, and information about missing observations and model assumptions. These details allow assessment of both precision and robustness.
Finally, the primary evaluation and extension periods answer different questions. The primary period compares the named treatment groups, while the extension includes ravulizumab in both sequences. Keeping treatment periods and sequences distinct is essential when interpreting longer-term safety or efficacy data. The registry offers safety counts by period but does not report the efficacy estimates needed to assess the main statistical objective.
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 main limitation for interpreting efficacy is that the registry record does not report the primary outcome estimates or confidence interval. It also does not report the noninferiority margin. As a result, the central study objective cannot be evaluated from the posted information, and no conclusion about the direction, magnitude, or precision of the primary contrast can be drawn.
The allocation field is NA even though the official title describes randomization. The record explicitly flags the arms as not a like-for-like control comparison. Details of allocation, concealment, and the handling of any baseline imbalance are not reported in the registry record. This leaves uncertainty about the comparability of groups and the causal interpretation of a treatment contrast.
The study was open-label, with masking listed as none. The registry does not describe safeguards for assessments or analysis that might reduce the effects of treatment knowledge. The primary outcome is a laboratory measure, but no further assessment procedures are reported in the registry record.
Information about missing observations, discontinuations, adherence, and the number included in each analysis is not reported. The Full Analysis Set is defined, but its analyzed size and the treatment of missing data are not given. Nor are model diagnostics, sensitivity analyses, or multiplicity procedures reported. These gaps limit assessment of robustness.
The extension period involves treatment sequences in which participants initially assigned to eculizumab could receive ravulizumab. Extension outcomes would therefore not represent a continued comparison of the original treatments. The registry lists safety counts but does not provide exposure-adjusted comparisons or detailed event definitions. These limitations are specific to interpretation of this record and do not establish whether the analyses were conducted or reported elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: ALXN1210 Versus Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab — NCT03056040.
- Registry record last updated 2025-03-12; status last verified 2025-02.
- Results first posted 2019-03-21.
- 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
The record describes a completed Phase 3, open-label, active-controlled, parallel study in adults with PNH who were clinically stable after at least 6 months of eculizumab treatment. Enrollment was 202. The primary evaluation period lasted 26 weeks and compared ravulizumab with eculizumab; an extension period allowed ravulizumab treatment for up to 4 years.
The primary endpoint was percent change in LDH from baseline to Day 183, analyzed using an MMRM with specified treatment, visit, baseline LDH, and transfusion-history terms. The study objective was noninferiority, but the primary estimates, confidence interval, and noninferiority margin are not reported in the registry record.
The record lists secondary clinical and patient-reported outcomes and gives serious and other adverse event counts by period and treatment sequence. It describes the official study title as randomized, while allocation is NA and the arms are flagged as not a like-for-like control comparison. Missing-data methods, multiplicity procedures, and further allocation details are not reported in the registry record.