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 OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE) (NCT05139810), a randomized phase 3 study. The primary outcome is Time-Normalized Investigator-Confirmed (IC) HAE Attack Rate (Per Month) From Week 1 to Week 25.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05139810 |
| Phase | Phase 3 |
| Condition | Hereditary Angioedema |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 91 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Ionis Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The trial enrolled participants with hereditary angioedema type I or type II. The primary analysis population was the FAS: randomized participants who received at least 1 dose of donidalorsen or placebo. The registry record reports 91 enrolled participants; the primary endpoint results include 22 participants in pooled placebo, 45 in Cohort A, and 23 in Cohort B.
Intervention
Donidalorsen 80 mg was given by subcutaneous injection on either an every-4-weeks schedule in Cohort A or an every-8-weeks schedule in Cohort B. Cohort A received doses at Weeks 1, 5, 9, 13, 17, and 21. Cohort B received doses at Weeks 1, 9, and 17.
Comparator
Pooled placebo combined participants assigned to placebo in Cohort A and Cohort B. Placebo was administered subcutaneously on the corresponding every-4-weeks or every-8-weeks schedule. The registry record states that placebo data were pooled for comparison with donidalorsen, as prespecified in the protocol and statistical analysis plan.
Primary question
The primary question was whether the time-normalized rate of investigator-confirmed hereditary angioedema attacks from Week 1 to Week 25 differed between pooled placebo and each donidalorsen schedule. The endpoint expresses attacks as a rate per month, rather than simply counting attacks without accounting for participants’ contributed time. The trial also assessed attack patterns, attack-free status, other attack measures, and quality of life.
3. Trial Design
OASIS-HAE (NCT05139810) was a Phase 3, randomized, quadruple-masked, parallel-group study of donidalorsen in participants with hereditary angioedema. The registry lists 91 participants as enrolled and the study status as completed. The recorded study start was 2021-12-03, and primary completion was 2023-11-09. The sponsor was Ionis Pharmaceuticals, Inc.
Participants were assigned to pooled placebo or to one of two donidalorsen 80 mg schedules. Cohort A received subcutaneous treatment every 4 weeks, at Weeks 1, 5, 9, 13, 17, and 21. Cohort B received subcutaneous treatment every 8 weeks, at Weeks 1, 9, and 17. Placebo participants followed one of those two schedules. For the primary comparison, the placebo participants from both cohorts were pooled. The registry describes that pooling as prespecified in the protocol and statistical analysis plan.
The primary outcome was the time-normalized investigator-confirmed attack rate from Week 1 to Week 25. The analysis population was the FAS, defined in the registry as all randomized participants who received at least 1 dose of study drug. The primary result lists 22 participants in pooled placebo, 45 in Cohort A, and 23 in Cohort B. The reasons that these outcome-specific counts differ from the overall enrollment are not reported in the registry record.
The registry lists 8 outcome measures and 18 analyses. Secondary outcomes covered attack rates and attack characteristics, attack-free status, clinical response, acute treatment use, angioedema control, and quality of life. The available results do not report every listed secondary outcome. Details of the allocation procedure, the exact masking roles, and other protocol procedures 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: A total of 91 participants were enrolled and randomized in the study. Out of 91, 1 participant withdrew consent prior to receiving the study drug. As pre-specified in the protocol and statistical analysis plan, for purposes of analysis, data for placebo participants from Cohort A and Cohort B was pooled for comparison to donidalorsen treated participants.
Overall Study
| Stage | Pooled Placebo | Cohort A: Donidalorsen 80 mg | Cohort B: Donidalorsen 80 mg |
|---|---|---|---|
| STARTED | 22 | 46 | 23 |
| Full Analysis Set (FAS) | 22 | 45 | 23 |
| COMPLETED | 0 | 1 | 3 |
| NOT COMPLETED | 22 | 45 | 20 |
Reasons for not completing this period:
| Reason | Pooled Placebo | Cohort A: Donidalorsen 80 mg | Cohort B: Donidalorsen 80 mg |
|---|---|---|---|
| Voluntary Withdrawal | 2 | 1 | 0 |
| Pregnancy | 1 | 0 | 0 |
| Roll Over to CS7 | 19 | 44 | 20 |
Analysis population for the primary outcome, as defined in the registry: The FAS included all randomized participants who received at least 1 dose of the study drug (donidalorsen or placebo). As pre-specified in the protocol and statistical analysis plan, for purposes of analysis, data for placebo participants from Cohort A and Cohort B was pooled for comparison to donidalorsen treated participants.
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: The FAS included all randomized participants who received at least 1 dose of the study drug (donidalorsen or placebo). As pre-specified in the protocol and statistical analysis plan, for purposes of analysis, data for placebo participants from Cohort A and Cohort B was pooled for comparison to donidalorsen treated participants.
| Characteristic | Unit | Pooled Placebo | Cohort A: Donidalorsen 80 mg | Cohort B: Donidalorsen 80 mg | Total |
|---|---|---|---|---|---|
| Participants analysed | 22 | 45 | 23 | 90 | |
| Age, Continuous | years | 35.4 (SD 11.03) | 39.6 (SD 15.23) | 34.1 (SD 13.22) | 37.2 (SD 13.88) |
| Sex: Female, Male: Female | Participants | 8 | 28 | 12 | 48 |
| Sex: Female, Male: Male | Participants | 14 | 17 | 11 | 42 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 2 | 3 | 6 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 21 | 43 | 20 | 84 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Race – American Indian or Alaskan Native | Participants | 2 | 0 | 1 | 3 |
| Race/Ethnicity, Customized: Race – Asian | Participants | 0 | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Race – Black or African American | Participants | 1 | 1 | 0 | 2 |
| Race/Ethnicity, Customized: Race – White | Participants | 18 | 42 | 22 | 82 |
| Race/Ethnicity, Customized: Race – Multiple | Participants | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Race – Other | Participants | 0 | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Time-Normalized Investigator-Confirmed (IC) HAE Attack Rate (Per Month) From Week 1 to Week 25, measured over Week 1 to Week 25.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | HAE attacks per month |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the time-normalized investigator-confirmed hereditary angioedema attack rate per month from Week 1 to Week 25. The registry defines the rate by counting attacks during the assessment period, dividing by the number of days each participant contributed, and expressing the result on a 28-day basis. This approach accounts for differences in contributed observation time, so the result is a rate rather than a raw total count.
An attack required signs or symptoms consistent with an event in at least one of the specified locations. These included peripheral angioedema, such as cutaneous swelling involving an extremity, face, neck, torso, or genitourinary region; abdominal angioedema, with abdominal pain and possible accompanying symptoms; or laryngeal angioedema, with specified airway, speaking, swallowing, throat, or oral-area symptoms. The endpoint therefore focuses on investigator-confirmed attacks meeting the registry definition, not every symptom or health event.
Rates are useful when participants contribute different amounts of observation time. A rate ratio then compares the modeled attack rates between groups. These measures describe event frequency during the stated period; they do not by themselves describe attack severity, the experience of every participant, or outcomes outside the assessment window.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results show lower estimated time-normalized attack rates in both donidalorsen groups than in pooled placebo. The reported least-squares mean rate was 2.26 HAE attacks per month for pooled placebo, with a 95% confidence interval from 1.657 to 3.085. For Cohort A, the estimate was 0.44, with a 95% confidence interval from 0.265 to 0.727; for Cohort B, it was 1.02, with a 95% confidence interval from 0.651 to 1.594.
The registry’s Poisson regression analyses report an attack rate ratio of 0.19 for Cohort A compared with pooled placebo, with a 95% confidence interval from 0.107 to 0.351 and p < 0.001. For Cohort B, the reported ratio was 0.45, with a 95% confidence interval from 0.261 to 0.777 and p = 0.004. Both confidence intervals are below 1, the value corresponding to equal modeled rates. These are model-based comparisons for the stated endpoint and period.
A confidence interval conveys the uncertainty around an estimate under the analysis assumptions. The intervals are not a guarantee that the true effect lies within the reported range, and they do not capture every possible source of uncertainty, such as limitations in measurement or missing information. The p-values quantify compatibility with a null comparison under the model; they do not measure the size or importance of an effect.
The primary finding concerns attack rate, not all dimensions of hereditary angioedema. It does not establish what happened after Week 25, whether individuals experienced the group-average pattern, or how the results apply to people outside the study population. The two dosing schedules are distinct randomized comparisons against pooled placebo; the posted primary results do not report a direct statistical comparison between Cohort A and Cohort B. The estimates should therefore be read as evidence about each schedule relative to the shared placebo group, rather than as a formal ranking of the schedules.
Secondary outcomes provide additional context, including attack-free status and angioedema control, but they do not replace the primary endpoint. Their interpretation is constrained by the number of outcomes and analyses and by the lack of a reported multiplicity procedure. Some posted secondary comparisons are simple unadjusted recalculations, while the registry includes a model-based analysis for attack-free status. The results from those different approaches address related but not identical statistical measures.
9. Statistical Methods Explained
The primary endpoint is a rate, so the registry reports a Poisson regression model for the comparison between each donidalorsen cohort and pooled placebo. Poisson regression is a general statistical method for modeling event counts. In a rate analysis, the model can account for how long participants contribute observation time, allowing the comparison to reflect events per unit of time rather than only the total number of events. The registry describes the endpoint’s time adjustment through participant days contributed and a 28-day rate basis.
The model’s reported measure is an attack rate ratio. A ratio of 1 represents equal modeled rates between the two groups; a value below 1 represents a lower modeled rate in the donidalorsen group relative to pooled placebo. The registry reports a separate ratio for Cohort A and Cohort B. Because both comparisons use pooled placebo, the estimates share a comparator, but they remain separate comparisons. A result for one cohort does not establish a direct difference between the two donidalorsen schedules.
The arm-level results are least-squares mean rates with 95% confidence intervals. A least-squares mean is a model-based estimate, not necessarily the simple arithmetic average of individual participant rates. The confidence interval describes precision under the fitted model and its assumptions. A narrower interval indicates less statistical uncertainty around the estimate than a wider interval, but precision alone does not establish clinical importance. The registry lists no separate standard deviation for these rates.
Poisson regression is designed for count data. A general consideration in count modeling is over-dispersion: the observed variability may exceed what a basic Poisson model assumes. If that occurs, uncertainty estimates from a model that does not account for it can be inaccurate. Whether over-dispersion was assessed, and whether any adjustment was used, is not reported in the registry record. Other details of the fitted model, including covariates and model diagnostics, are also not reported in the registry record.
The FAS included randomized participants who received at least 1 dose of study drug. The record states that the pooling of placebo participants from Cohort A and Cohort B for the primary comparison was prespecified in the protocol and statistical analysis plan. This explains the shared placebo comparator, but does not establish how every other analysis decision was made. Further information about the treatment of missing endpoint data, participants with incomplete observation, or deviations from assigned treatment is not reported in the registry record.
For binary secondary outcomes, a risk difference expresses the difference between the proportions meeting the outcome in two groups. Odds ratios and risk ratios are alternative measures, with distinct interpretations. Logistic regression estimates an odds ratio, while the unadjusted recalculations use the observed group counts to estimate risk differences. These quantities are not interchangeable: odds compare the odds of an outcome, whereas a risk difference compares proportions directly. A model-based odds ratio may also differ from an unadjusted comparison because the methods and estimands differ.
Confidence intervals for binary outcomes reflect uncertainty in the estimated contrast. When the interval includes the null value for that measure, the data do not provide strong evidence against an equal-group comparison under that method and its assumptions. A p-value is not a probability that the null hypothesis is true. Nor does a thresholded p-value describe the range of plausible effect sizes; the point estimate and confidence interval are needed to understand magnitude and precision.
The secondary sample-size calculations are planning illustrations derived from observed effects, not the trial’s own design justification and not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrations consider detecting 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The listed values are participants per arm for 80% power and participants per arm for 90% power. Such calculations depend on the observed effect and assumptions; they do not show the probability that this completed study detected an effect. The original sample-size justification is not reported in the registry record.
What do the confidence intervals communicate?
They show the uncertainty associated with an estimate under the statistical model. They should be read alongside the point estimate and the outcome definition. They do not account for every design, measurement, or reporting limitation, and they are not individual-level predictions.
Why distinguish the reported and recalculated analyses?
The registry’s model-based comparisons and simple unadjusted recalculations can use different statistical measures. For example, a logistic regression odds ratio is not the same estimand as an unadjusted risk difference. Differences between their estimates or p-values do not necessarily indicate an error; they can reflect the methods’ different targets and assumptions.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Poisson regression model | IC HAE attack rate ratio 0.19 | 0.107 to 0.351 | < 0.001 |
| Poisson regression model | IC HAE attack rate ratio 0.45 | 0.261 to 0.777 | =0.004 |
The registry reports the sponsor’s primary comparisons using Poisson regression, with attack rate ratios, 95% confidence intervals, and p-values for Cohort A and Cohort B versus pooled placebo. These model-based comparisons are the primary inferential results recorded for the attack-rate endpoint. The primary results give both the group-specific least-squares mean rates and the regression comparisons.
No separate recalculated primary comparison is reported in the available results. The registry does not flag a discrepancy between the sponsor analysis and a recalculation. For the primary endpoint, interpretation should therefore center on the posted Poisson regression estimates and their stated uncertainty, while recognizing that model details beyond the method name are not reported in the registry record.
For attack-free status, the sponsor’s reported analyses use logistic regression and odds ratios. The simple recalculations use unadjusted risk differences based on observed counts. Those estimates answer related, but not identical, questions, so they should not be treated as interchangeable replications. The registry does not report a sponsor analysis for the AECT outcome in the results available for this comparison. The distinction between model-based sponsor results and unadjusted recalculations matters particularly for secondary outcomes, where the method affects the measure and its uncertainty.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists 8 outcome measures and 18 analyses, including a primary attack-rate endpoint and several secondary outcomes. Testing multiple outcomes or comparisons raises a multiplicity issue: even if each test uses a conventional threshold, the chance of at least one false-positive result across a collection of tests can increase. Common approaches include prespecifying a testing hierarchy or adjusting significance thresholds, but which approach was used must come from the analysis plan. Beyond the stated pooling, the multiplicity strategy is not reported in the registry record.
The record identifies a protocol and statistical analysis plan and says that pooling placebo participants across Cohort A and Cohort B was prespecified. It does not report enough detail to determine the complete order of testing, whether the primary endpoint controlled the testing of secondary outcomes, or whether any p-values were adjusted. As a result, the secondary p-values should not be interpreted as though a multiplicity correction had been established.
The primary analysis population is described as randomized participants who received at least 1 dose of study drug. This definition identifies the FAS used for the primary endpoint, but other details of the analysis population and handling of treatment discontinuation are not reported in the registry record. The record does not describe how missing attack diaries or other missing endpoint measurements were handled, whether missingness was imputed, or whether sensitivity analyses examined alternative assumptions. The reasons that outcome-specific counts vary are also not reported in the registry record.
Missing-data methods matter because an analysis can be influenced if participants with incomplete follow-up differ from those with complete follow-up, or if missingness relates to attack experience. Without the stated methods and sensitivity analyses, the effect of missing information on the reported estimates cannot be assessed from the registry results alone. The same caution applies to other unreported elements of the statistical plan, including model diagnostics and any prespecified subgroup analyses.
12. 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 |
|---|---|---|---|
| Pooled Placebo | 1 | 22 | 4.5% |
| Cohort A: Donidalorsen 80 mg | 0 | 45 | 0.0% |
| Cohort B: Donidalorsen 80 mg | 0 | 23 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pooled Placebo | 0 of 22 |
| Cohort A: Donidalorsen 80 mg | 0 of 45 |
| Cohort B: Donidalorsen 80 mg | 0 of 23 |
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 |
|---|---|
| Pooled Placebo | 15 of 22 |
| Cohort A: Donidalorsen 80 mg | 22 of 45 |
| Cohort B: Donidalorsen 80 mg | 13 of 23 |
Most frequent serious adverse event terms
| Event term | Organ system | Pooled Placebo | Cohort A: Donidalorsen 80 mg | Cohort B: Donidalorsen 80 mg |
|---|---|---|---|---|
| Limb Injury | Injury, poisoning and procedural complications | 1 of 22 | 0 of 45 | 0 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pooled Placebo | Cohort A: Donidalorsen 80 mg | Cohort B: Donidalorsen 80 mg |
|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 5 of 22 | 6 of 45 | 3 of 23 |
| Headache | Nervous system disorders | 4 of 22 | 7 of 45 | 2 of 23 |
| Influenza | Infections and infestations | 2 of 22 | 4 of 45 | 5 of 23 |
| Upper Respiratory Tract Infection | Infections and infestations | 1 of 22 | 4 of 45 | 3 of 23 |
| Injection Site Erythema | General disorders | 0 of 22 | 6 of 45 | 1 of 23 |
| Urinary Tract Infection | Infections and infestations | 0 of 22 | 4 of 45 | 2 of 23 |
| Back Pain | Musculoskeletal and connective tissue disorders | 1 of 22 | 3 of 45 | 1 of 23 |
| Covid-19 | Infections and infestations | 3 of 22 | 1 of 45 | 1 of 23 |
| Injection Site Discolouration | General disorders | 0 of 22 | 3 of 45 | 1 of 23 |
| Gastroenteritis | Infections and infestations | 2 of 22 | 1 of 45 | 1 of 23 |
Serious events with the highest arm-level rate: limb injury (4.5%).
The registry reports serious adverse events in 1 of 22 participants in pooled placebo, 0 of 45 participants in Cohort A, and 0 of 23 participants in Cohort B. No deaths were recorded in any of the three groups. Limb Injury is listed as the top serious adverse event term, at 4.5%. These counts are descriptive and arise from groups of different sizes.
The registry also reports other adverse events in 15 of 22 participants in pooled placebo, 22 of 45 in Cohort A, and 13 of 23 in Cohort B. These figures are not a comparison of event severity or causality. The record does not establish from these counts alone whether an event was caused by study treatment, and the detailed event descriptions, exposure-adjusted rates, and statistical comparisons are not reported in the registry record.
Rare serious events are difficult to characterize precisely from small group counts. Zero recorded events in a group does not establish that the risk is zero, and a single event does not establish a difference between groups. These safety figures describe what the registry recorded during the study; they do not support conclusions about unreported events or longer-term safety.
13. What the Result Does, and Does Not, Mean
The primary results describe the rate of investigator-confirmed hereditary angioedema attacks during Week 1 to Week 25 in the analyzed trial groups. The reported group estimates and Poisson regression comparisons show lower modeled attack rates for each donidalorsen schedule than for pooled placebo during that period. The confidence intervals quantify statistical uncertainty under the reported model.
These findings do not mean that every participant in a donidalorsen group had fewer attacks than every participant receiving placebo. Group-level rates do not describe each person’s experience. Nor do the results establish what happens outside the study’s assessment period, in populations not represented in the trial, or under schedules not studied. A statistical comparison also does not by itself establish the importance of an observed difference to participants.
The two donidalorsen schedules were each compared with the shared pooled placebo group. The primary results do not report a direct test comparing the schedules with one another. Differences between their point estimates should not be treated as proof that one schedule is superior to the other without a direct comparison and its uncertainty.
Secondary outcomes add information about other aspects of attacks and disease control, but the registry does not provide numerical results for every listed secondary measure. The record also does not report a multiplicity procedure, detailed missing-data methods, or the full statistical analysis plan. These gaps limit how strongly secondary findings and the robustness of the overall analysis can be characterized.
The trial result is therefore best understood as a set of randomized group comparisons for a defined endpoint and time window, rather than a universal statement about treatment response, long-term outcomes, or individual benefit. The registry record supports statistical description of the reported data; it does not replace clinical judgment or provide individual medical advice.
14. Why This Trial Matters Statistically
This trial is statistically informative because it evaluates an event-rate endpoint rather than relying only on a single end-of-study measurement. The time-normalized rate accounts for participant time contributed to observation and gives a direct description of attack frequency over the stated period. The registry’s attack definition also makes clear that the endpoint counts investigator-confirmed events meeting specified clinical criteria.
The design includes two dosing schedules and a shared pooled placebo comparator. That structure allows each schedule to be evaluated against placebo, while also requiring readers to distinguish those comparisons from a head-to-head comparison. Reporting each group’s estimated rate alongside the rate ratio and confidence interval helps readers consider both the scale of the endpoint and the uncertainty in the comparative estimate.
Statistical interpretation also depends on what is missing from the record. The trial lists a range of secondary outcomes, but the available results do not include numerical findings for all of them. The multiplicity approach, detailed missing-data handling, and several model details are not reported. These limitations illustrate why a small p-value or a favorable direction across outcomes should not be read in isolation from the design and analysis plan.
The results also show why distinctions among statistical measures matter. A rate ratio for attack counts, an odds ratio for a binary outcome, and a risk difference each answer different questions. Their estimates should be interpreted according to their outcome definition and method, rather than combined as if they were the same measure. The planning illustrations offer a separate lesson: calculations based on observed effects can inform future planning scenarios, but they are not observed power and do not reveal the study’s original design rationale.
15. 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 analysis includes 22 participants in pooled placebo, 45 in Cohort A, and 23 in Cohort B. These group sizes frame the precision of the estimates, as reflected in their confidence intervals. The registry reports 91 participants enrolled, but the reason that the primary endpoint counts do not account for the full enrollment is not reported in the registry record. The available information does not allow that difference to be attributed to missing data, nonreceipt of treatment, or another cause.
The registry identifies Poisson regression for the primary comparisons but does not report the model specification, covariates, diagnostics, or whether over-dispersion was assessed. It also does not report detailed methods for handling incomplete attack records, missing endpoint data, or changes in treatment exposure. Those details would help assess the assumptions underlying the estimates.
The placebo group pools participants assigned to two schedules, as described as prespecified in the protocol and statistical analysis plan. The record does not provide enough information to assess whether the pooled comparison had other planned conditions or how schedule-specific placebo results might have behaved. The primary results compare each donidalorsen cohort against pooled placebo and do not report a direct schedule-to-schedule test.
Interpretation of secondary findings is limited by unreported numerical results for several listed outcomes and by the absence of a reported multiplicity strategy. The numerical secondary comparisons also include unadjusted recalculations that differ in measure from the sponsor’s logistic-regression odds ratios. Details of the original sample-size justification are not reported in the registry record; the planning illustrations based on observed effects cannot fill that gap.
Finally, the primary endpoint covers Week 1 to Week 25. The record’s posted primary result does not describe outcomes beyond that window, and the safety counts alone do not establish longer-term event patterns or causality.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE) — NCT05139810.
- Registry record last updated 2025-03-06; status last verified 2025-02.
- Results first posted 2025-03-06.
- 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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19. Record Summary
OASIS-HAE (NCT05139810) was a completed, randomized, quadruple-masked, parallel-group Phase 3 study sponsored by Ionis Pharmaceuticals, Inc. It enrolled participants with hereditary angioedema and compared donidalorsen 80 mg given every 4 weeks or every 8 weeks with pooled placebo.
The primary outcome was the time-normalized investigator-confirmed attack rate per month from Week 1 to Week 25. The registry reports Poisson regression comparisons of each donidalorsen cohort with pooled placebo, with both reported rate ratios below 1. The secondary outcomes address attack status and other measures of disease control and quality of life, although numerical results are not reported for all listed outcomes.
The record reports serious adverse event counts and no deaths. It does not report detailed missing-data methods, a multiplicity procedure, or several model details needed to assess analysis assumptions more fully. The results should be read as comparisons for the specified groups, endpoint, and period.