Study of AOC 1001 in Adult Myotonic Dystrophy Type 1 (DM1) Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of AOC 1001 in Adult Myotonic Dystrophy Type 1 (DM1) Patients (NCT05027269), a randomized phase 1, phase 2 study. The primary outcome is Frequency of Treatment Emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled Phase 1/2 study. The registry describes quadruple masking and a sequential study model. Its stated aim was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple intravenous doses of AOC 1001 in adults with DM1. The registry lists Avidity Biosciences, Inc. as the sponsor and the study status as completed.

The study had two parts. Part A was a single-dose design with one dose-level cohort. Participants received either 1 mg/kg AOC 1001 once or saline placebo once. The described treatment period was one day, followed by six months of follow-up; the stated patient duration was six months.

Part B was a multiple-ascending-dose design with two dose-level cohorts. The listed AOC 1001 groups received 2 mg/kg or 4 mg/kg, and the placebo group received saline. The arm descriptions specify three administrations. The described treatment period was three months, followed by three months of follow-up; the stated patient duration was six months.

The registry lists enrollment as 39 and gives the study start as 2021-10-28 and primary completion as 2023-02-14. Those record-level details do not establish how many participants were analyzed for each endpoint, or whether everyone completed follow-up. Those analysis and completion counts are not reported in the registry record. The posted outcome groups are presented separately for the two parts, so their results should be read in the context of the different dosing schedules and placebo groups rather than treated as one simple dose comparison.

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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Frequency of Treatment Emergent Adverse Events (TEAEs), measured over Through study completion, up to Day 183.

The primary endpoint is the frequency of treatment-emergent adverse events, expressed as the cumulative number of participants with an event by the end of the study. The stated timeframe is through study completion, up to Day 183. A participant count addresses whether an event occurred at least once; it does not describe how many events each participant experienced, how long events lasted, or how severe they were unless those details are separately reported.

Safety endpoints are used in early-phase studies to describe tolerability and identify potential harms while dose regimens are being evaluated. In general, counting participants with at least one event is a straightforward way to summarize how commonly an event was recorded in each group. It is not, by itself, a causal estimate: events can occur during a study without being caused by the assigned intervention. Interpretation also depends on the study’s event definitions, observation time, completeness of follow-up, and the number of participants contributing data.

The posted primary results give group counts, with no confidence intervals or comparative test results. They therefore describe the observed event counts but do not quantify uncertainty around those counts or establish a statistical difference between groups. The registry record does not report further details about endpoint adjudication or how events were attributed to treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary endpoint is binary at the participant level: a participant either had at least one treatment-emergent adverse event during the stated timeframe or did not. The displayed result is the number of participants with an event, alongside the group size. This is a count summary, not a continuous measurement such as a laboratory value and not a count of every event episode. A participant with multiple events still contributes as one participant to this endpoint if the endpoint is based on whether any event occurred.

What does a participant count tell the reader?

As a descriptive statistic, the count makes clear how many participants in each group met the event definition. It is easy to interpret, but it does not by itself convey the precision of an underlying event frequency. In general, uncertainty depends on the number of participants observed and the number with events. A confidence interval would communicate a range of plausible values under a specified statistical model; no such interval is posted for the primary results. No comparative p-value or treatment-effect estimate is posted either.

The record’s analysis information indicates that a two-arm comparison for this binary endpoint was not available or estimable. Consequently, inferential comparisons between active treatment and placebo should not be reconstructed from the displayed counts. A re-calculation could only be a simple, unadjusted calculation based on posted summaries; it could not reproduce an analysis that used participant-level data, adjusted for design features, or followed a sponsor-specified method. The record does not report such an analysis, and the listed primary results do not contain a sponsor comparison to take precedence.

Why do design features matter?

Part A and Part B have different dosing schedules and different placebo groups. Part A examines a single administration, while Part B examines repeated administrations and has two dose levels. The Part B placebo is described as pooled. These features mean that the groups should be interpreted within their study part and regimen. A comparison that ignores the parts, dosing schedule, or pooling would mix groups that were not described as a single common comparison.

Randomization is intended, in general, to reduce systematic differences between assigned groups. It does not guarantee balance in every characteristic, especially when groups are small. Masking can reduce the influence of expectations on assessment and reporting, but the registry description alone does not establish how masking was maintained or whether it was successful. The record does not report the randomization procedure, allocation ratio, stratification factors, or details of the masking process.

What can planning calculations say?

In general, a sample-size calculation estimates how many participants a future study might need under specified assumptions about the effect to detect, variability or event frequency, significance level, and power. Such a calculation is a planning exercise, not an observed result. The planning assumptions recorded for this study describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of an observed effect. The registry record does not report the study’s own sample-size justification, and planning illustrations based on observed results are not observed power. They should not be interpreted as evidence that this trial had a particular probability of detecting an effect.

For a binary endpoint, an event frequency and an assumed comparison are central to planning. The posted information does not provide an estimable two-arm comparison for this endpoint, so the participant counts alone should not be treated as a precise planning effect. Any planning illustration depends on assumptions and is not a substitute for a trial’s prespecified design rationale. The registry record does not report the target effect, planned power, or a formal sample-size justification for the trial.

What uncertainty remains?

Counts can be affected by missing observations and differing time at risk. The primary timeframe runs through study completion, up to Day 183, but the registry information does not state how missing safety data were handled, whether participants with incomplete follow-up were included, or how the analysis population was defined. General methods may address incomplete data through prespecified rules, but no such rules should be assumed for these results.

The endpoint also combines different event types. This makes it a broad indicator of whether any treatment-emergent event was recorded, rather than a detailed measure of event burden. A richer safety interpretation would depend on event descriptions, severity, seriousness, timing, duration, and relationship to treatment. Those details are not all represented in the primary endpoint. The separate serious-event summary adds some information, but does not supply comparative uncertainty or establish causation.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Part A Single Dose: 1 mg/kg AOC 1001", "Part A Single Dose: Placebo", "Part B Multiple Dose: 2 mg/kg AOC 1001", "Part B Multiple Dose: 4 mg/kg AOC 1001", "Part B Multiple Dose: Pooled Placebo")
n      <- c(6, 2, 9, 13, 8)
events <- c(6, 1, 9, 13, 7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Part A Single Dose: 1 mg/kg AOC 1001  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Part A Single Dose: Placebo  2  1  50.0  1.3  98.7  9.5  90.5  9.4  90.6
ARM  Part B Multiple Dose: 2 mg/kg AOC 1001  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7
ARM  Part B Multiple Dose: 4 mg/kg AOC 1001  13  13  100.0  75.3  100.0  77.2  100.0  76.8  99.8
ARM  Part B Multiple Dose: Pooled Placebo  8  7  87.5  47.3  99.7  52.9  97.8  51.8  97.2

11. Multiplicity, Missing Data and Analysis Populations

The study lists safety, pharmacokinetic, and pharmacodynamic outcomes. The registry record identifies nine outcome measures and eight posted secondary outcomes, but it does not report a multiplicity strategy for interpreting results across those measures. In general, when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase. Statistical approaches may control that risk or may distinguish confirmatory from exploratory outcomes, but the registry record does not report which approach, if any, was used.

The record lists no analyses for the posted results. It does not report a prespecified statistical analysis plan, analysis populations, or details of how participants were included in each outcome analysis. It also does not report whether outcomes were analyzed according to randomized assignment, treatment received, or another population definition. Such choices can affect the interpretation of randomized trial results and should not be inferred from the group labels alone.

Missing-data handling is not reported in the registry record. In general, incomplete follow-up can matter for safety outcomes because participants observed for different periods have different opportunities for events to be recorded. The stated primary timeframe is through study completion, up to Day 183, but the record does not describe how incomplete observations, withdrawals, or unavailable endpoint data were handled.

The registry does not report interim analyses, stopping rules, or a sample-size justification. Those details cannot be assumed from the completed status or the enrollment listing. In the absence of these methods details, the posted counts are best treated as descriptive summaries and not as a basis for claims about adjusted, multiplicity-controlled, or missing-data-robust treatment effects.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory failure (11.1%), thalmus haemorrhage (7.7%).

The serious adverse event record lists zero serious events among 6 participants in the Part A 1 mg/kg AOC 1001 group, zero among 2 participants in the Part A placebo group, one among 9 participants in the Part B 2 mg/kg group, one among 13 participants in the Part B 4 mg/kg group, and zero among 8 participants in the Part B pooled placebo group. The recorded death count is zero for each group. These are group-level counts, not evidence that an event was caused by or unrelated to treatment.

The registry also lists “Respiratory Failure” at 11.1% and “Thalmus haemorrhage” at 7.7% among the top serious terms. It does not specify in the information recorded which study group those terms correspond to, nor does it explain the calculation or denominator for those percentages. The Part B 2 mg/kg serious-event listing spells the drug name as “ACO 1001,” while the corresponding outcome arm is labeled AOC 1001.

Serious adverse events are distinct from the primary endpoint, which counts participants with any treatment-emergent adverse event. These summaries do not give event timing, severity beyond seriousness, duration, attribution, or a comparative statistical analysis. With small groups and no posted uncertainty estimates, the counts should be read as descriptive safety information rather than as a precise comparison.

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

The posted results establish what the registry reports about treatment-emergent adverse events in each study group: the count of participants with at least one event and the recorded group size. They also show the recorded serious adverse event and death counts by group. These summaries are relevant to the study’s stated focus on safety and tolerability, and they make the observed group-level data explicit.

They do not establish whether AOC 1001 caused any particular event. The endpoint is treatment-emergent, meaning it concerns events observed during the treatment-emergent timeframe; the record does not provide a treatment-relatedness judgment for each event. Nor do the counts establish how treatment affects DM1 symptoms or function. The primary endpoint is not an efficacy outcome, and the posted primary results do not compare clinical benefit.

The counts also do not provide a precise estimate of the difference between AOC 1001 and placebo. No confidence interval or comparative analysis is reported for the primary endpoint, and a two-arm binary comparison is listed as unavailable or not estimable. General statistical interpretation: when groups are small, observed counts can be unstable, and uncertainty is important when comparing groups. Without a reported estimate and its uncertainty, the direction or size of a treatment effect cannot be reliably quantified from these summaries.

The design’s parts should remain distinct in interpretation. Part A involved a single administration, whereas Part B involved multiple administrations at two dose levels and a pooled placebo group. The record does not report a formal test of dose response or a combined comparison across parts. The results therefore do not support ranking dose regimens statistically.

The record includes planned aims concerning pharmacokinetics and pharmacodynamics, but those aims are not substitutes for the posted primary safety outcome. The registry information identifies relevant secondary outcome categories, while detailed analyses and their uncertainty are not reported. Overall, these data are descriptive findings from a completed early-phase study; they do not by themselves resolve comparative safety, causation, or efficacy questions.

14. Why This Trial Matters Statistically

This trial is statistically notable because it combines an early-phase safety focus with randomized and masked comparisons across single-dose and multiple-dose regimens. The design produces several distinct treatment groups rather than one simple active-versus-placebo contrast. That structure matters: the single-dose Part A groups and multiple-dose Part B groups have different exposure schedules, and the placebo groups are specific to each part, with the Part B placebo pooled. Interpreting the outcomes requires preserving those distinctions.

The primary endpoint is a participant-level event count, an accessible summary for an early-phase safety question. Its simplicity also sets limits. It records whether a participant experienced an event, not the full event burden, event severity, or treatment attribution. The additional serious adverse event counts provide a narrower safety perspective, but they remain descriptive group counts without an accompanying comparative model or uncertainty estimate.

Small group sizes make precision especially important. An observed count can change substantially in meaning depending on how many participants were followed and for how long, and the record does not report confidence intervals or an estimable two-arm comparison for this endpoint. The analysis therefore illustrates why a randomized design does not automatically make every posted group contrast statistically conclusive. Randomization supports a comparison in principle; the analysis method, amount of information, and uncertainty determine what can be concluded.

The registry also describes pharmacokinetic and pharmacodynamic aims, which are relevant to understanding exposure and biological response in an early-phase study. However, the posted primary safety counts cannot answer those questions. Keeping endpoint purpose, study-part structure, and uncertainty in view helps prevent descriptive safety findings from being read as evidence of efficacy or as a definitive comparison among regimens.

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 posted primary results consist of participant counts and group sizes, with no confidence intervals or inferential comparison. The registry indicates that values were missing or not estimable for a two-arm comparison of this binary endpoint. As a result, the observed counts do not quantify the precision of a treatment-versus-placebo contrast.

The groups are small and differ in size. Part A and Part B also differ in dosing schedule, and Part B uses a pooled placebo group. These design features limit simple cross-group comparisons. The registry record does not report whether analyses adjusted for study part or other design features, or whether a dose-response comparison was planned.

The record does not report how many participants contributed data to each analysis beyond the group sizes attached to the posted outcome, nor does it explain missing-data handling, withdrawals, or the definition of analysis populations. Follow-up duration is described, but the record does not give participant-level time at risk or confirm completeness of follow-up for each group.

Further limitations include the absence of reported endpoint adjudication details, event-relatedness assessments, a statistical analysis plan, multiplicity procedures, interim-analysis information, and a sample-size justification. The serious-event term percentages are listed without an explanation of their denominator or group attribution. The Part B 2 mg/kg safety listing also uses “ACO 1001” where the outcome arm uses “AOC 1001.” These gaps mean that the results are best interpreted as registry-level descriptive safety summaries, not as a complete statistical analysis of comparative effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of AOC 1001 in Adult Myotonic Dystrophy Type 1 (DM1) Patients — NCT05027269.
• Registry record last updated 2026-09-28; status last verified 2026-09.
• Results first posted 2026-09-28.
• 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.

19. Record Summary

The registry describes a randomized, double-blind, placebo-controlled Phase 1/2 study of intravenous AOC 1001 in adults with DM1. It used a single-dose Part A and a multiple-ascending-dose Part B, with saline placebo groups. Enrollment is listed as 39, and study status is completed.

The primary endpoint counts participants with treatment-emergent adverse events through study completion, up to Day 183. The posted results report group counts and sizes, along with separate serious adverse event and death counts. No inferential analysis is posted for the primary endpoint, and a two-arm binary comparison is listed as unavailable or not estimable. The registry record does not report the analysis plan, missing-data methods, or sample-size justification. The results should therefore be read as descriptive safety information rather than a precise comparative estimate.