An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy (NCT03921528), a randomized phase 2 study. The primary outcome is Cohort 1: Change From Baseline in the Revised Hammersmith Scale (RHS) Total Score at Day 364 (Visit 15) [Month 12].

2. Clinical Question

3. Trial Design

TOPAZ (NCT03921528) is a Phase 2 active-treatment study of SRK-015 in patients with later-onset spinal muscular atrophy. The registry lists randomized allocation, no masking, and a parallel model. Enrollment is recorded as 58, and the study status is completed. The recorded start date is 2019-04-22, and primary completion is recorded as 2021-01-19.

The study description covers pediatric and adult patients with SMA Type 2 and Type 3. It separates participants into cohorts according to SMA type and ambulatory status: Cohort 1 is ambulatory Type 3 SMA; Cohort 2 is Type 2 SMA or non-ambulatory Type 3 SMA; and Cohort 3 is Type 2 SMA. The primary endpoint is restricted to Cohort 1. Its two posted groups are Cohort 1 monotherapy and Cohort 1 dual therapy. Outcome data for the other cohorts are not included in the primary comparison.

The registry lists SRK-015 as the intervention but does not identify the additional component of dual therapy in its intervention listing. It also does not report further details about the randomization procedure, allocation concealment, or the intended role of a control group. Because masking is listed as none, the study was open-label according to the registry classification; this can matter for outcomes involving clinical assessment or participant performance.

The study includes a range of motor-function and mobility outcomes. The primary measure is the Revised Hammersmith Scale total score at month 12 in ambulatory Type 3 participants. Secondary outcomes include other RHS time points, categories of RHS change, walking and timed tasks in Cohort 1, and HFMSE outcomes in Cohorts 2 and 3. The registry record does not report the original sample-size justification or further details of the study's statistical plan.

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

Analysis population for the primary outcome, as defined in the registry: The ITT Population: all enrolled/randomized patients who receive at least 1 dose of study drug. The ITT Population was the main population for analysis of efficacy endpoints; the analysis includes all assessments from all patients with the exception of assessments after missing 3 consecutive doses due to site access restrictions caused by COVID-19. The last observation carried forward (LOCF) method was used to impute the 12-month primary endpoint for data missing for other reasons.

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: Intent-to-Treat (ITT) Set: All participants who were enrolled/randomized and received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Cohort 1: Change From Baseline in the Revised Hammersmith Scale (RHS) Total Score at Day 364 (Visit 15) [Month 12], measured over Baseline up to 12 months.

The primary endpoint is change from baseline in the Revised Hammersmith Scale total score at Day 364, described as month 12, for Cohort 1. The RHS is a 36-item clinical assessment of physical abilities in patients with Type 2 SMA and ambulatory or non-ambulatory Type 3 SMA. The stated primary endpoint population is ambulatory Type 3 patients in Cohort 1, described as 5-21 years of age.

The RHS ranges from a minimum achievable score of 0 to a maximum achievable score of 69. Most items are graded on a scale of 0, 1, or 2, while the remaining items are scored 0 or 1. Higher total scores indicate increased motor function, and a positive change from baseline indicates improvement. Using change rather than a single follow-up score makes the endpoint a measure of how the score differs from each participant's baseline assessment.

A motor-function scale is relevant to this study because the trial concerns SMA and evaluates physical abilities. The RHS is intended to capture those abilities in the populations described in the registry. However, a group mean change does not show how individual participants changed, and a numerical change alone does not establish whether that change is important to patients. The registry record does not report a threshold for interpreting clinically meaningful change.

7. Results Posted in the Registry

• Cohort 1 - Dual Therapy: mean 0.00 versus -0.10 on control; difference 0.10 (95% CI -3.20 to 3.40), standardized effect d = 0.03; z-test p = 0.953.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Cohort 1: Change From Baseline in 30-Second Sit-to-Stand

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Cohort 1 - Dual Therapy: mean -0.20 versus -0.60 on control; difference 0.40 (95% CI -1.06 to 1.86), standardized effect d = 0.22; z-test p = 0.592.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort 1 - Dual Therapy and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering additional RHS time points, degrees of RHS change, and several mobility or timed tasks for Cohort 1, as well as HFMSE outcomes for Cohorts 2 and 3. These measures add different views of motor function and performance, but they do not all assess the same construct in the same population. In particular, outcomes from the other cohorts cannot be treated as direct replications of the Cohort 1 primary endpoint.

The available record does not support a broad claim that secondary findings consistently reinforce or contradict the primary result. Although secondary outcome names are listed and one Cohort 1 secondary comparison has posted summary statistics, the registry reports no analyses in its analysis count and provides no reported-analysis entries for the listed secondary outcomes. The individual secondary results should therefore be interpreted only where actual estimates are posted, rather than inferred from the outcome names or the primary result.

Secondary endpoints can help assess whether a primary finding is accompanied by changes in related measurements, but they generally carry less weight when numerous outcomes are considered without a reported multiplicity strategy. Testing many outcomes increases the opportunity for at least one apparently notable result to arise by chance. An unadjusted secondary p-value does not account for that broader set of tests. Without a prespecified hierarchy or adjustment method in the registry record, isolated secondary findings should be treated as exploratory rather than as independent confirmation.

The primary RHS result remains the main efficacy comparison identified in the record. Secondary outcomes may provide context, but their interpretation depends on the population, timing, measurement properties, completeness of data, and analysis plan. Those details are not all available in the registry record. The listed outcomes consequently describe the breadth of the assessment more clearly than they establish an overall pattern of efficacy.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Cohort 1:Change From Baseline in the Revised Hammersmith Scale (RHS) Total Score at Other Prespecified Timepoints
• Cohort 1: Proportion of Patients Achieving Various Magnitudes of Change in RHS Score From Baseline
• Cohort 1: Change From Baseline in 6-Minute Walk Test (6MWT)
• Cohort 1: Change From Baseline in 30-Second Sit-to-Stand
• Cohort 1: Change From Baseline in 10-Meter Walk/Run (From RHS)
• Cohort 1: Change From Baseline in Timed Rise From Floor (From RHS)
• Cohort 2 &3: Change From Baseline in HFMSE Total Score at Other Prespecified Timepoints
• Cohort 2 & 3: Proportion of Patients Achieving Various Magnitudes of Change in HFMSE Score From Baseline

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a score change, and the registry reports the mean and standard deviation for each group. A mean is the arithmetic average of the observed changes. The standard deviation describes how spread out individual changes are around that average. These summaries are useful for comparing groups, but a mean can conceal variation in individual responses and does not show the distribution of scores.

What does the mean difference represent?

The mean difference is calculated as the dual-therapy group mean change minus the monotherapy group mean change. A positive value therefore means the posted average change was higher in the dual-therapy group; on the RHS, positive change is described as improvement. This direction convention does not by itself establish a clinically important benefit. The comparison is expressed in RHS score points, not as a percentage change or a standardized score.

For the primary endpoint, the reported group means are -0.1 and 0.0, and the mean difference is 0.1. The comparison also reports a pooled standard deviation of 3.922 and a standardized difference, d, of 0.025. A standardized difference expresses the group separation relative to the pooled variability, so it can help describe the scale of a contrast without using RHS points. It does not replace the original score units or determine whether the difference matters clinically.

Why report a confidence interval?

A confidence interval describes a range of effect estimates reasonably compatible with the observed data under the statistical model used to construct it. It is not a range containing a fixed proportion of individual participant outcomes, and it is not the probability that the true effect lies inside the particular interval. The primary comparison's interval, from -3.196 to 3.396, communicates the uncertainty around the estimated mean difference. Because it includes zero, the data do not sharply distinguish a difference from no difference. Its width also shows why the point estimate alone should not be treated as definitive.

What does the p-value add?

The reported p-value is unadjusted. Under the statistical model and a null hypothesis of no group difference, it measures how inconsistent the observed result is with that null model. It is not a measure of effect size, precision, or clinical relevance. It does not state the probability that the null hypothesis is true. An unadjusted value also does not account for the possibility that many outcomes or comparisons were examined. The registry record does not report a multiplicity adjustment plan.

The registry describes the endpoint summary as a mean with standard deviation and supplies a between-group mean-difference estimate. The record does not report enough information to fully reconstruct the analysis, such as the model specification, treatment of baseline score in the comparison, or any covariate adjustment. These details should not be inferred from the summary statistics alone. The record's description of the ITT population states that it includes enrolled/randomized patients who received at least one dose and that it was the main population for efficacy analyses. It also mentions an exception for assessments after missing 3 consecutive doses, but the description is truncated, so the full rule is not reported in the registry record.

Why can variability and over-dispersion matter?

General statistical explanation: when participant outcomes vary substantially, the mean difference is estimated less precisely unless the study has enough information to characterize that variation. A model that assumes less variation than is actually present can produce standard errors that are too small and confidence intervals that are too narrow. Over-dispersion refers generally to observed variability exceeding what a statistical model expects. The registry record does not state that over-dispersion was assessed or used as a model feature in this trial, so it should not be assumed to have occurred.

The posted group standard deviations differ, and the sample sizes in the two primary groups are small. That makes the estimate sensitive to the particular observations in each group. The confidence interval is therefore important alongside the point estimate: it expresses uncertainty that is not captured by saying only that the mean difference was 0.1. The registry record does not report a prespecified analysis plan, an interim analysis plan, or the assumptions used in the trial's original design.

11. Confidence Intervals and Precision

The primary estimate is a mean difference of 0.1 RHS points, with a 95% confidence interval from -3.196 to 3.396. The point estimate is close to zero, but the interval is considerably wider than the point estimate. It includes zero as well as negative and positive differences, so the data do not establish the direction of a possible difference between groups. The confidence interval gives a more complete account of uncertainty than the point estimate alone.

A confidence interval is an interval produced by a statistical procedure that, under its assumptions, would cover the underlying effect at the stated rate over repeated use of that procedure. It is not a probability statement about the one fixed underlying effect after the data have been observed. Nor does the interval describe the range of changes among individual participants. It concerns the estimated difference between group means.

Precision depends on the amount of information and the variability in the data, among other features of the analysis. The posted primary groups have 11 and 12 participants, with standard deviations of 5.01 and 2.56. Those summaries help explain why the estimated group difference should be read with uncertainty rather than as a stable, exact value. The record does not report additional details that would allow independent assessment of the interval's model assumptions.

The interval should not be interpreted as demonstrating equivalence. The registry record does not report an equivalence margin, and the interval includes effects in both directions. It also does not identify a threshold for a clinically important RHS difference. Thus, statistical precision and clinical importance cannot be collapsed into a single judgment from the reported interval. The evidence is best described as an imprecise estimate centered near zero, not as proof that the groups have identical outcomes.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial's original design calculation. For continuous outcomes such as this one, the figures are participants per arm, not a total across arms or a total number of events. The planning assumptions listed in the registry record are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect to detect is the stated fraction of the observed effect.

The 80% power column describes the estimated participants per arm for a future study to have an 80% chance of detecting the assumed effect under those assumptions, if that effect and the model assumptions are correct. The 90% power column uses a higher chance of detection and therefore requires a larger planned sample under the same assumptions. The rows scale the assumed effect to 100%, 75%, and 50% of the observed effect. As the assumed effect becomes smaller, more participants are needed to distinguish it from random variation.

The primary comparison's planning figures are very large. That follows from using the small observed mean difference as the effect to detect, together with the observed variability and the stated planning assumptions. This does not mean the original trial required or enrolled those numbers; the registry record does not report the trial's own sample-size justification or original design assumptions. The planning estimates are not observed power. They are hypothetical sample-size calculations that use the observed effect as an input, and they should not be interpreted as a retrospective measure of how likely the completed study was to find an effect.

These calculations are especially sensitive when the observed effect is small or unstable. A different assumed effect, variability, allocation, analysis, or significance level would produce different planning estimates. The registry record does not report a planned clinically meaningful RHS difference, so the observed-effect fractions should not be treated as established clinical targets.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.100; pooled standard deviation σ = 3.922.
2. n = 2 × (1.96 + 0.842)² × 3.922² / 0.100² = 24,151.4, rounded up to 24,152 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.1                      # observed difference in means
sigma <- 3.92240572438225                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3921528)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 24,152 (80% power), 32,332 (90% power)
 75% of observed effect: n per arm = 42,936 (80% power), 57,479 (90% power)
 50% of observed effect: n per arm = 96,606 (80% power), 129,328 (90% power)
power.t.test: 24152.4 
Simulated power at n = 24,152 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study assesses multiple outcomes, time points, subgroups, or comparisons. Each statistical test carries a possibility of a false positive under its null hypothesis; with many tests, the overall chance of at least one apparently significant result can increase. Methods such as a prespecified testing hierarchy or statistical adjustment can address this issue, but the registry record does not report whether such methods were planned or used. The posted p-value for the primary comparison is explicitly unadjusted, and the record does not describe a multiplicity strategy for the secondary outcomes.

The registry lists 13 outcome measures and 11 posted secondary outcomes. The range of measures and time points makes it important to know which outcomes were prespecified, how they were ordered, and whether any adjustment was planned. The record identifies the primary endpoint, but does not report a complete statistical analysis plan or enough detail to determine how the full family of tests was handled. Accordingly, isolated secondary findings, if considered, should be interpreted cautiously.

Missing-data handling is also relevant for change-from-baseline outcomes. The registry's ITT description defines the main efficacy population as enrolled/randomized patients who received at least one dose, and says the analysis includes assessments from all such patients except assessments after missing 3 consecutive doses. The description ends mid-sentence, so the full exception and its implementation are not reported in the registry record. The record does not provide the amount or pattern of missing endpoint data, the method used to handle missing measurements, or sensitivity analyses assessing the effect of missingness.

The trial's exact analysis population for the posted primary summary and the consequences of any exclusions are therefore not fully clear from the registry record. Randomized allocation is reported, but details about analysis according to assigned group, handling of treatment adherence, and the use of any adjusted model are not reported. These gaps limit assessment of how closely the posted estimate follows the randomized comparison and how robust it is to missing outcome data.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: scoliosis surgery (33.3%), pneumonia (20.0%), scoliosis (20.0%), gait inability (18.2%), upper respiratory tract infection (10.0%).

The registry reports serious adverse events by group, using the number at risk and the number affected. In Cohort 1, serious adverse events were reported for 4 of 11 participants in monotherapy and 4 of 12 in dual therapy. In Cohort 2, 9 of 15 were affected; in Cohort 3 low dose, 6 of 10; and in Cohort 3 high dose, 5 of 10. No deaths were reported in the listed groups.

These are counts of participants affected, not a comparison adjusted for differences between groups or an estimate of a causal treatment effect. The cohorts differ in their descriptions, and only the Cohort 1 groups form the primary efficacy comparison. Serious-event percentages listed by term include scoliosis surgery, pneumonia, scoliosis, gait inability, upper respiratory tract infection, and acute respiratory failure. The registry record does not give enough context in the posted term list to interpret those percentages as comparative risks across the treatment groups.

Safety summaries should be read separately from efficacy results. The record gives event counts but does not provide detailed timing, severity beyond the serious-event classification, attribution, or exposure-adjusted analyses in the registry record. These data describe reported events during the study; they do not by themselves establish whether an event was caused by study treatment.

16. What the Result Does, and Does Not, Mean

The primary result describes the average month-12 RHS change in two Cohort 1 groups. The group means are close, and the estimated mean difference is 0.1 points. The confidence interval spans negative and positive values, so the result does not determine the direction of a possible difference with precision. The unadjusted p-value does not provide evidence of a clear between-group difference under the stated comparison, but it is not proof that the groups are equivalent.

The result applies to the defined Cohort 1 comparison, not automatically to Cohort 2, Cohort 3, or all patients with later-onset SMA. The study included patients described across Type 2 and Type 3 SMA and different ambulatory statuses, while the primary endpoint addresses ambulatory Type 3 participants. The findings also concern a scale-based motor-function measure at a specific follow-up time, not every aspect of health or function.

The RHS score has an interpretation defined in the record: higher scores indicate increased motor function, and positive change indicates improvement. However, the registry does not state a clinically meaningful difference threshold. A statistically estimated difference therefore cannot be translated from this record alone into a judgment about the importance of a change for patients. Group averages also do not show whether participants had similar responses or varied substantially.

The trial is described as randomized, which is relevant to comparing groups, but the registry record does not report the randomization method, full analysis plan, or complete missing-data procedures. It also does not identify the additional component of dual therapy in the intervention listing. These limitations restrict interpretation of what precisely differs between the groups and how the reported estimate was obtained.

In short, the posted result is an imprecise estimate centered close to zero for the stated endpoint and population. It neither establishes a meaningful advantage for either group nor demonstrates that no meaningful difference exists. Broader conclusions about treatment effects, other SMA populations, or unreported outcomes are not justified by this endpoint alone.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate, an uncertainty interval, and the study context need to be read together. The primary mean difference is close to zero, but the confidence interval covers values in both directions. A statement based only on the point estimate would understate uncertainty; a statement based only on the unadjusted p-value would also miss how much the data leave unresolved.

The endpoint is a clinically oriented motor-function scale, but score direction and clinical importance are separate questions. The registry explains that higher RHS scores indicate increased motor function and that a positive change indicates improvement. It does not report a threshold for a clinically meaningful change. Statistical interpretation can therefore describe the estimated difference and its precision, but cannot establish the practical importance of that difference from the posted record alone.

The trial also shows how population definitions shape the scope of a result. The overall study covers several cohort descriptions, whereas the primary comparison concerns ambulatory Type 3 SMA in Cohort 1. A result for that comparison should not be generalized without qualification to the other cohorts. Cohort-specific outcomes and analyses matter in a study that includes different SMA types and ambulatory statuses.

Finally, the record lists multiple secondary outcomes and provides planning illustrations based on the observed effect. These raise distinct statistical questions: how to interpret multiple unadjusted tests, how missing measurements were handled, and how a small observed difference should inform future sample-size planning. The record does not fully answer those questions. Recognizing what is reported and what remains unspecified is part of drawing appropriately bounded conclusions from a clinical trial record.

18. 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 comparison is based on small Cohort 1 groups, and the confidence interval is broad relative to the point estimate. The resulting estimate is imprecise, and group means do not reveal the participant-level distribution of change. The registry record does not report a clinically meaningful RHS threshold, which limits interpretation of the score difference in practical terms.

The trial is listed as open-label, with no masking. Knowledge of group assignment can affect performance or assessment, particularly for clinical and functional measures. The record does not report whether any outcome assessors were otherwise masked. Randomized allocation is listed, but the randomization procedure and allocation concealment are not described in the registry record.

The intervention listing names SRK-015, while the Cohort 1 outcome groups are labelled monotherapy and dual therapy. The additional component of dual therapy is not identified in the intervention list. This makes the precise treatment contrast difficult to characterize from the registry record alone. The record also does not state whether the primary analysis adjusted for baseline score or other variables, or give sufficient details to reconstruct the model.

Missing-data rules are incompletely described: the ITT population definition is truncated after mentioning assessments following missing 3 consecutive doses. The extent and pattern of missingness, the analysis method for missing outcomes, and sensitivity analyses are not reported. The record does not describe multiplicity handling despite listing multiple outcomes, and does not give the original sample-size rationale or statistical analysis plan. These gaps limit assessment of robustness and of how closely the posted summaries correspond to the intended analysis.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy — NCT03921528.
• Registry record last updated 2024-12-02; status last verified 2024-11.
• Results first posted 2022-11-17.
• 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.

22. Record Summary

NCT03921528, TOPAZ, is a completed Phase 2 randomized, open-label, parallel study of SRK-015 in later-onset SMA Type 2 and Type 3. The record lists enrollment of 58 and three cohorts defined by SMA type and ambulatory status.

The primary endpoint is change from baseline in RHS total score at month 12 for ambulatory Type 3 SMA in Cohort 1. The posted mean difference between dual therapy and monotherapy is 0.1, with a confidence interval from -3.196 to 3.396 and an unadjusted p-value of 0.953. The estimate is close to zero but imprecise, and the interval includes values in either direction.

The record lists multiple secondary outcomes and serious adverse event counts across the cohorts. Important details—including the full statistical analysis plan, original sample-size rationale, full missing-data rule, and the additional component of dual therapy—are not reported in the registry record.