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 A Study to Evaluate Lumasiran in Adults With Recurrent Calcium Oxalate Kidney Stone Disease and Elevated Urinary Oxalate Levels (NCT05161936), a randomized phase 2 study. The primary outcome is Percent Change in 24-hour Urinary Oxalate From Baseline to Month 6.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05161936 |
| Phase | Phase 2 |
| Condition | Recurrent Calcium Oxalate Kidney Stone Disease, Elevated Urinary Oxalate Levels |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alnylam Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Adults with recurrent calcium oxalate kidney stone disease and elevated urinary oxalate levels. The registry record lists enrollment as 2. It does not report participant characteristics such as age, sex, baseline urinary oxalate values, or the number assigned to each group.
Intervention
Lumasiran, administered by subcutaneous injection. The record identifies Lumasiran Dose 1 and Lumasiran Dose 2 as separate groups, but does not report the dose amounts or enough detail to describe their schedules.
Comparator
Placebo administered by subcutaneous injection. The study is described as randomized, triple-masked, and parallel. The record does not specify the allocation ratio or identify which roles were masked.
Primary question
The primary question was whether lumasiran affected the percent change in 24-hour urinary oxalate from baseline to Month 6. The record says that no participant data were collected for this outcome because the study terminated early. It therefore does not provide an estimate of the primary effect.
The registry also lists secondary outcomes: the percentage of patients achieving at least a 20% reduction in 24-hour urinary oxalate from baseline to Month 6, and percent change in urinary calcium oxalate supersaturation over the same period. Their presence in the record does not establish that they were measured or analyzed. No outcome analyses are listed. The available record consequently describes the question the trial was designed to investigate, but does not answer whether urinary oxalate changed in the study groups.
3. Trial Design
This was a Phase 2, randomized, triple-masked, parallel study sponsored by Alnylam Pharmaceuticals. The registry lists three groups: Lumasiran Dose 1, Lumasiran Dose 2, and placebo. Participants in each group were to receive the assigned drug by subcutaneous injection. The record does not state the dose amounts, treatment schedule, duration of assigned treatment, allocation ratio, or which participants or study personnel were masked.
The study concerned adults with recurrent calcium oxalate kidney stone disease and elevated urinary oxalate levels. Its primary purpose was to evaluate the effect of lumasiran on percent change in urinary oxalate excretion. The primary endpoint was defined as percent change in 24-hour urinary oxalate from baseline to Month 6. The listed secondary outcomes concerned a reduction threshold in urinary oxalate and change in urinary calcium oxalate supersaturation.
The registry reports a start date of 2022-01-27, a primary completion date of 2022-11-01, and a status of terminated. It lists enrollment as 2. The reason for termination, the timing of the decision, and any operational circumstances surrounding it are not reported in the registry record. The record explicitly states that early termination meant no participant data were collected for the primary outcome.
Randomization is intended to reduce systematic differences between treatment groups, while masking can limit the influence of treatment knowledge on care, measurement, and reporting. These are general design principles; the record does not give enough information to assess how randomization or masking was implemented in this study. With no primary endpoint observations reported and no outcome analyses listed, the design description should not be mistaken for evidence of a treatment effect.
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 | Lumasiran Dose 1 | Lumasiran Dose 2 | Placebo |
|---|---|---|---|
| STARTED | 1 | 0 | 1 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 1 | 0 | 1 |
Reasons for not completing this period:
| Reason | Lumasiran Dose 1 | Lumasiran Dose 2 | Placebo |
|---|---|---|---|
| Study terminated by Sponsor | 1 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: No participant data was collected for this outcome measure due to early study termination.
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: No participants were enrolled or treated with Lumasiran Dose 2.
| Characteristic | Unit | Lumasiran Dose 1 | Lumasiran Dose 2 | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 1 | 0 | 1 | 2 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 0 | 0 | 1 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 1 | 1 |
| Age, Continuous | years | 52 (52 to 52) | — | 65 (65 to 65) | 58.5 (52 to 65) |
| Sex: Female, Male: Female | Participants | 1 | — | 0 | 1 |
| Sex: Female, Male: Male | Participants | 0 | — | 1 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | — | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | — | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | — | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | — | 0 | 0 |
| Race (NIH/OMB): White | Participants | 1 | — | 1 | 2 |
| 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: Belgium | participants | 1 | — | 0 | 1 |
| Region of Enrollment: United States | participants | 0 | — | 1 | 1 |
| Region of Enrollment: Italy | participants | 0 | — | 0 | 0 |
| Region of Enrollment: United Kingdom | participants | 0 | — | 0 | 0 |
| Region of Enrollment: Switzerland | participants | 0 | — | 0 | 0 |
| Region of Enrollment: Spain | participants | 0 | — | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change in 24-hour Urinary Oxalate From Baseline to Month 6, measured over Baseline to Month 6.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was percent change in 24-hour urinary oxalate from baseline to Month 6. A 24-hour urine measurement represents oxalate excretion over a full collection period; expressing change as a percentage relates the follow-up value to the participant’s baseline value. This can be useful when participants begin with different baseline levels, because the endpoint focuses on relative change rather than only the follow-up measurement. That is a general explanation of the measure, not a claim about the trial’s analysis method.
Urinary oxalate was a relevant measurement for the stated study population because elevated urinary oxalate levels were part of the condition being studied, and the primary purpose was to evaluate lumasiran’s effect on urinary oxalate excretion. The endpoint is a biochemical measure; it is not itself a count of kidney stone events. The record does not report a result linking changes in this measure to stone recurrence in this study.
For this trial, the registry defines the measurement period as baseline to Month 6, but states that no participant data were collected for the outcome because of early termination. There is therefore no reported baseline-to-follow-up change, group contrast, uncertainty interval, or test result for the primary endpoint. The intended endpoint can be described, but its observed value and the size or direction of any treatment effect cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical finding is an absence of primary outcome data, not a measured null effect. The registry explicitly states that no participant data were collected for the percent change in 24-hour urinary oxalate from baseline to Month 6 because the study terminated early. As a result, there is no reported estimate comparing either lumasiran dose group with placebo on the primary endpoint.
No primary endpoint effect estimate, confidence interval, or p value is reported. A confidence interval would ordinarily describe the range of effect values compatible with the data under an analysis model; without outcome observations and an analysis, there is no such interval to interpret. Likewise, the record does not support a conclusion that groups were similar or different. An unobserved effect is not evidence of no effect, and it is not evidence of benefit.
The registry lists enrollment as 2 and reports 0 outcome analyses. Those details underscore the limited outcome information available, but they do not permit reconstruction of the primary result. The record does not say how enrollment was distributed among the three groups, and no group-specific urinary oxalate measurements are reported. It is therefore not possible to assess balance at baseline, describe within-group changes, or estimate a comparative treatment effect.
The secondary outcomes are listed as planned measures, but the record does not report their results or analyses. Their inclusion cannot be taken as evidence that either outcome was collected. In particular, the urinary oxalate reduction threshold and the urinary calcium oxalate supersaturation measure cannot fill the primary endpoint gap without reported observations and an analysis.
The termination status is important context for interpreting the missing endpoint, but the reason for termination is not reported in the registry record. Nothing in the reported information establishes whether termination was related to safety, recruitment, operations, or another cause. Any explanation would be speculation.
Overall, the record documents a trial design and intended outcomes, along with early termination and absent primary endpoint data. It does not provide an efficacy estimate or the precision needed to judge one. The appropriate statistical reading is that the primary treatment comparison is unavailable, rather than that a comparison was conducted and found no difference.
9. Statistical Methods Explained
What does the primary endpoint measure?
The primary endpoint is percent change in 24-hour urinary oxalate from baseline to Month 6. In general, percent change expresses a follow-up value relative to a starting value. A full 24-hour collection is intended to capture excretion over that collection period. The registry identifies the measurement and timeframe, but does not specify the formula, collection procedures, number of collections, or rules for validating a collection. Those details are not reported in the registry record.
The primary endpoint is not reported as a kidney stone event outcome. It measures urinary oxalate, while the stated disease concerns recurrent calcium oxalate kidney stone disease. A biomarker can be useful for studying a biological response, but interpretation of the biomarker does not by itself establish a change in clinical events. No relationship between an observed biomarker change and stone recurrence is reported for this study.
What can randomization and masking tell readers?
Randomization is a general method for assigning participants to groups in a way intended to limit systematic differences in prognosis and other characteristics. In a parallel design, assigned groups are followed as separate groups rather than each participant receiving every study condition in sequence. Masking is generally used to reduce the influence of knowledge about assignment on participant experience, clinical management, outcome measurement, and assessment. These descriptions explain the design terms; they do not verify how well these protections worked in this trial.
The record calls the study randomized, triple-masked, and parallel, but does not describe sequence generation, concealment of assignment, or which roles were masked. It also does not report the allocation ratio. Thus, readers can identify the intended design, but cannot audit its implementation from the registry information available.
Why is there no effect estimate to interpret?
An effect estimate requires observed outcome information and a defined comparison. Here, the registry explicitly says there were no participant data for the primary outcome due to early study termination, and it lists 0 outcome analyses. Accordingly, there is no reported change within a group or contrast between a lumasiran group and placebo. No confidence interval or p value is reported for the primary outcome.
In general, a confidence interval communicates uncertainty around an estimate, while a hypothesis test assesses compatibility between observed data and a specified null hypothesis under assumptions. Neither can be interpreted when the relevant outcome estimate is unavailable. A missing result should not be described as a statistically nonsignificant result: nonsignificance would require an analysis, whereas the record says the primary outcome was not collected.
How should the planning assumptions be read?
The sample-size planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detecting a stated fraction of an observed effect. It also distinguishes participant counts per arm from total event counts for time-to-event settings. These are planning assumptions, not evidence about what happened in this trial. The record does not report the trial’s own sample-size justification or protocol-based power calculation.
Planning calculations ask how much information a future study might need under specified assumptions. They are not observed power, and they do not establish that the present study could detect an effect. They also depend on an effect size and other assumptions that may not hold in a future setting. Since the primary outcome has no participant data in this record, the observed primary effect needed to ground an effect-based planning illustration is not available in the reported outcome information. No numerical sample-size planning result is stated in the registry entries.
Over-dispersion is a general concern when outcome variability exceeds what a simple statistical model assumes. If it is present and not accommodated, standard errors and confidence intervals may be misleading. The registry record does not report a statistical model, dispersion assessment, or adjustment for over-dispersion. It is therefore not possible to say whether this issue arose or how it was handled.
What analysis details remain unknown?
The record does not describe the primary analysis model, covariate adjustment, analysis population, missing-data method, or multiplicity procedure. It does not report interim analyses or a monitoring plan. These features should not be inferred from the Phase 2 label, randomized design, or listed outcomes. The absence of those details limits assessment of the planned analysis, while the absence of primary outcome data prevents a result-level assessment regardless of the model that might have been intended.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study evaluates several outcomes, time points, treatment comparisons, or statistical tests. In general, testing multiple hypotheses can increase the chance of at least one apparently positive result under a collection of null effects. Researchers may address this through a prespecified hierarchy, adjustment procedure, or a clearly limited set of confirmatory comparisons. The registry lists one primary outcome and two secondary outcomes, but the procedure for handling multiplicity is not reported in the registry record. No analyses are listed, so there are no reported p values or outcome claims whose multiplicity adjustment can be assessed.
The registry identifies the primary outcome timeframe as baseline to Month 6 and says no participant data were collected for that outcome because of early termination. It does not report whether the secondary outcomes were collected, how missing measurements would have been handled, or whether any sensitivity analyses were planned. A missing-data method cannot recover an endpoint that the record says was not collected; more generally, methods for incomplete observations depend on why and how data are missing, which is not described.
The analysis population is also not reported. The record does not specify whether the intended analysis was based on randomized assignment, treatment received, or another population definition. It does not describe exclusions, adherence rules, or the treatment of participants without follow-up measurements. These details are relevant to interpreting a randomized comparison, but no analysis population can be attributed to this trial from the available record.
The absence of endpoint data and analyses means there is no result to evaluate for multiplicity, missing-data sensitivity, or population selection. These unknowns should not be replaced with assumptions about standard practice.
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 |
|---|---|---|---|
| Lumasiran Dose 1 | 0 | 1 | 0.0% |
| Placebo | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Lumasiran Dose 1 | 0 of 1 |
| Lumasiran Dose 2 | 0 of 0 |
| Placebo | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lumasiran Dose 1 | 1 of 1 |
| Lumasiran Dose 2 | 0 of 0 |
| Placebo | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lumasiran Dose 1 | Lumasiran Dose 2 | Placebo |
|---|---|---|---|---|
| Type 2 Diabetes Mellitus | Metabolism and nutrition disorders | 1 of 1 | n/a of 0 | 0 of 1 |
| Cough | Respiratory, thoracic and mediastinal disorders | 0 of 1 | n/a of 0 | 1 of 1 |
The adverse-event record reports serious adverse events by study group as counts of participants at risk and counts affected. For Lumasiran Dose 1, 1 participant was at risk and 0 were affected by a serious adverse event. For placebo, 1 participant was at risk and 0 were affected. For Lumasiran Dose 2, the record lists 0 at risk and 0 affected. Deaths are reported as 0 in each group. No serious adverse-event terms are listed.
These are small, descriptive counts, not precise estimates of comparative safety. The record does not report a formal statistical comparison, confidence intervals, follow-up duration by participant, or enough information to establish the completeness of adverse-event collection. A count of 0 affected participants in a group does not demonstrate that risk is absent; it means no serious adverse event was recorded among the group’s reported at-risk count.
The record also lists other, non-serious adverse events: 1 participant at risk and 1 affected in Lumasiran Dose 1, and 1 at risk and 1 affected in placebo; Lumasiran Dose 2 has 0 at risk and 0 affected. These sparse counts should not be used to infer a reliable difference between treatments. The reason that the Dose 2 group has 0 participants at risk is not reported in the registry record. No causal conclusion about treatment and adverse events is supported by these figures.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, triple-masked, parallel Phase 2 study was designed to evaluate lumasiran against placebo in adults with recurrent calcium oxalate kidney stone disease and elevated urinary oxalate levels. It identifies two lumasiran dose groups and a placebo group, a primary urinary oxalate endpoint, and secondary urinary outcomes. It also reports that the study was terminated and that no participant data were collected for the primary endpoint because of early termination.
These registry entries describe the study’s purpose and its incomplete outcome record. They do not establish that lumasiran reduced or increased urinary oxalate, that either dose differed from placebo, or that urinary calcium oxalate supersaturation changed. No effect estimate, uncertainty interval, or inferential test is reported. The absence of a measured primary result cannot be interpreted as evidence that treatment had no effect.
The safety counts are also limited. They report few participants at risk in the groups with recorded exposure and do not support precise comparisons or broad conclusions about safety. The registry does not report the reason for termination, group assignment details, baseline characteristics, treatment schedules, or the analysis population. These gaps constrain interpretation without indicating why the information is absent.
The appropriate conclusion is narrow: the study was intended to assess a urinary biomarker, but the registry does not provide the primary outcome data needed to answer that question. The design and outcome definitions may inform understanding of the research question; they are not substitutes for observed results. Any broader conclusion about clinical effects, stone recurrence, or the balance of benefits and harms would go beyond what this record reports.
13. Why This Trial Matters Statistically
This trial is statistically notable because the registry documents a randomized, masked comparison but reports no participant data for its primary endpoint. It illustrates why a study’s design and a study’s results must be distinguished. Randomization and masking describe intended methods for producing a credible comparison; they do not create evidence of an effect when the outcome was not collected.
The primary measure was a change in 24-hour urinary oxalate from baseline to Month 6. That makes the intended question concrete: whether the urinary measure changed under the assigned study conditions. But an endpoint definition alone does not show how participants’ values changed, how much variability there was, or whether groups differed. Without those observations, precision and statistical uncertainty cannot be quantified.
The record also makes visible the limits of sparse safety counts. Counts by group can be reported descriptively, but a small number at risk does not permit a stable estimate of uncommon outcomes or a useful comparison of event rates. The entries should be read as what the registry records, not as a complete characterization of safety.
Finally, the study highlights the importance of transparent reporting about termination and analysis. The record states that termination occurred and that the primary outcome was not collected, but does not give the reason for termination or details of the intended statistical plan. Such information would help readers understand the context and distinguish planned methods from analyses that were actually possible. The present record supports a careful account of what was intended and what is unavailable, rather than a conclusion about efficacy.
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 principal limitation is that the registry explicitly reports no participant data for the primary endpoint because of early termination. With no primary outcome observations, the treatment effect and its precision cannot be estimated. The record also lists 0 outcome analyses, so no inferential results are available for the primary or secondary outcomes.
The reported enrollment is 2, but the record does not describe assignment by group or provide participant-level characteristics. It does not give baseline urinary oxalate values, follow-up measurements, treatment adherence, or the time each participant was observed. The listed adverse-event counts are correspondingly sparse and cannot support precise safety comparisons.
Important design and analysis details are not reported in the registry record, including the reason for termination, allocation ratio, dose amounts, treatment schedule, masking roles, analysis population, missing-data plan, and multiplicity procedure. The record also does not state the sample-size justification or describe interim analyses. These omissions prevent a full assessment of how the study was conducted and how an intended analysis would have been interpreted.
The secondary outcomes are listed, but their data collection and results are not reported. Their presence therefore does not resolve the lack of primary outcome information. Nor does the record establish a relationship between urinary biomarker changes and kidney stone events. These limitations make the available information descriptive of the trial’s design and status, rather than an estimate of treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate Lumasiran in Adults With Recurrent Calcium Oxalate Kidney Stone Disease and Elevated Urinary Oxalate Levels — NCT05161936.
- Registry record last updated 2024-05-22; status last verified 2024-04.
- Results first posted 2024-05-22.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a Phase 2, randomized, triple-masked, parallel study sponsored by Alnylam Pharmaceuticals. It evaluated two lumasiran dose groups and placebo in adults with recurrent calcium oxalate kidney stone disease and elevated urinary oxalate levels. Enrollment is listed as 2; the study began on 2022-01-27, has a primary completion date of 2022-11-01, and is marked terminated.
The primary outcome was percent change in 24-hour urinary oxalate from baseline to Month 6. The record states that no participant data were collected for this outcome because of early termination, and lists 0 outcome analyses. Two secondary outcomes are listed, but their results are not reported. The record does not state why the trial terminated. Adverse-event counts are recorded by group, but are too sparse to support precise comparisons.