Open-label Extension of the HOPE-2 Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-label Extension of the HOPE-2 Trial (NCT04428476), a na phase 2 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs) From Baseline Through Month 12.

2. Clinical Question

3. Trial Design

This is a Phase 2, multicenter, open-label extension of the HOPE-2 Duchenne Muscular Dystrophy trial. It enrolled 13 participants who had been in HOPE-2 and completed 12 months of follow-up. The study has a single-group design, with deramiocel as the intervention and no concurrent control arm described. Masking is listed as none. The study began on 2020-08-05, and the primary completion date is 2022-02-16. Its registry status is active, not recruiting.

The protocol description outlines repeated intravenous deramiocel infusions, with each infusion separated by 3 months. The arm description specifies 150 million Cardiosphere-Derived Cells per infusion. The initial open-label period is described as approximately 60 months, with assessments scheduled from screening and Day 1 through Month 60. Participants who complete all Month 60 assessments may be eligible to continue in a long-term open-label extension, receiving treatment every 3 months until commercial availability, study termination, or withdrawal or termination of participation. These statements describe the planned study structure; the record does not report actual exposure, visit completion, or long-term follow-up for individual participants.

Safety and efficacy assessments are described at regular study visits. The primary outcome is the number of participants with treatment-emergent adverse events from baseline through Month 12. Secondary measures include treatment-emergent adverse events at later time points and by severity, upper-limb function measured with PUL 2.0, and cardiac measures including left ventricular ejection fraction and indexed ventricular volumes. The registry lists 15 outcome measures, but no analyses are listed. The record does not report a randomized allocation procedure, a control condition, or a statistical analysis 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all participants who received investigational product.

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: Safety population included all participants who received investigational product.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs) From Baseline Through Month 12, measured over Baseline up to Month 12.

The primary endpoint is the number of participants with treatment-emergent adverse events from baseline through Month 12. An adverse event is defined in the record as an unfavourable and unintended sign, symptom, or disease associated in time with study-drug use, whether or not considered related to the drug. The definition includes abnormal laboratory findings. A treatment-emergent adverse event begins after treatment starts, or begins before treatment and worsens after treatment starts.

This endpoint is used to describe safety experience during the specified period. Counting participants with an event gives a direct description of how many people in the safety population experienced at least one qualifying event; it does not indicate the total number of event episodes or their duration. The record also defines serious adverse events by specified outcomes, including death, life-threatening events, persistent or significant disability, hospitalization, congenital anomaly or birth defect, or another medically important event. Seriousness is a classification and is distinct from whether an event is considered related to treatment.

The registry record identifies the safety population as all participants who received investigational product. It does not report an inferential analysis for the primary endpoint, an estimate of uncertainty, or a comparison group. The posted counts therefore describe the recorded safety experience without establishing a treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who receive the intervention. It can report how many participants experienced an event or how measurements changed over time, if those results are posted. Without a concurrent control group, it cannot directly estimate how outcomes would have differed under another treatment or under no treatment. This extension is described as single-group, with allocation listed as not applicable, so there is no randomized between-group contrast to interpret.

What does open-label mean for interpretation?

In general, open-label means treatment assignment is not masked from participants or study personnel. Knowledge of treatment can affect reporting, clinical assessments, decisions about care, or the timing and recording of events. These possibilities do not demonstrate that any particular result is biased; they are reasons to interpret uncontrolled, unmasked observations cautiously. The registry lists masking as none and does not report masking procedures for outcome assessment.

How should a participant count be understood?

A count of participants with an event records how many people met the event definition during the stated period. It is different from a count of event episodes: one participant may have more than one event, while the participant count still records that person once for the relevant outcome. A participant count also does not by itself describe severity, duration, timing, or whether the event was judged related to treatment. The record defines the primary outcome as a participant count of treatment-emergent adverse events from baseline through Month 12. Its safety population includes everyone who received investigational product.

What information does a confidence interval add?

In general, a confidence interval gives a range of values compatible with an estimate under the analysis assumptions and communicates statistical uncertainty. Narrower intervals indicate greater precision, while wider intervals indicate less precision. A confidence interval does not remove limitations in study design or show that a result is clinically important. No confidence interval is reported for the outcomes described in this registry record, and no inferential analysis is listed.

Why does the absence of a control group matter?

In general, a control group helps distinguish changes associated with an intervention from changes that might have occurred for other reasons. In an extension, participants have already reached a later stage of a preceding study and may differ from people who did not enter or continue. As a result, observed experiences in the extension may reflect selection as well as treatment exposure and the underlying condition. The record does not report an analysis that addresses these issues. Because the design is not randomized and has no like-for-like control group, comparative claims are not supported by the posted information.

What do the adverse-event categories convey?

The record defines serious adverse events through outcomes or clinical importance, while the primary endpoint includes treatment-emergent adverse events whether serious or non-serious. These concepts are not interchangeable: seriousness describes the event classification, whereas treatment emergence concerns timing in relation to treatment start. The posted safety entries separately list participants with serious events, other events, and deaths. The registry record does not provide event descriptions, event-level counts, attribution judgments, or enough detail to reconstruct how participants may appear across categories.

Can the record establish the planned analysis?

The registry describes outcomes and follow-up visits, but no analyses are listed. The statistical analysis plan, model specifications, handling of repeated observations, covariate adjustments, and interim analyses are not reported in the registry record. These details should not be inferred from the outcome names or the study schedule. In general, repeated measurements on the same participant are correlated, so an analysis of change over time should account for that dependence. Whether or how such methods were used in this study is not reported.

The registry record also does not report a sample-size justification. Any sample-size planning illustration based on an observed effect is not an observed-power calculation and cannot substitute for the study’s own design rationale. No outcome effect estimate or analysis result is listed from which to assess such an illustration. The appropriate statistical reading is therefore limited to the design descriptions and the posted participant counts, without extrapolating to unreported models, tests, or conclusions.

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("Deramiocel")
n      <- c(13)
events <- c(11)
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  Deramiocel  13  11  84.6  54.6  98.1  57.8  95.7  57.2  95.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including adverse-event outcomes, upper-limb function measures, and cardiac parameters at several follow-up visits. Considering many outcomes or time points raises a general multiplicity issue: the more hypotheses examined, the more opportunities there may be for apparently notable findings to arise by chance when formal tests are used. Methods such as prespecifying a primary analysis or adjusting for multiple testing can address this issue, but the registry record does not report a multiplicity strategy or an inferential analysis. No interpretation of statistical significance across outcomes is possible from the posted entries.

The record identifies the safety population as all participants who received investigational product. It does not describe analysis populations for the functional or cardiac outcomes, nor does it state how participants with missing visits or incomplete measurements were handled. The number of participants with available measurements at each visit is not reported in the registry record. It is also not reported whether missing values were imputed, excluded, or handled by a repeated-measures method.

In general, missing outcome data can affect interpretation when the probability of missingness is related to participants’ health or their measured outcomes. The direction and size of any such effect depend on the missingness pattern and analysis assumptions. Those details are not available, so the extent to which missing data could influence later-visit findings cannot be assessed. The registry’s planned follow-up schedule alone does not establish that all participants completed every assessment.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s safety entries list 0 participants with serious adverse events among 13 at risk for serious events, 11 participants with other adverse events among 13 at risk for those events, and 0 deaths in the Deramiocel group. These are participant counts, not a count of event episodes. The entries do not provide descriptions of individual events, their duration, severity beyond the serious-event classification, or whether they were judged related to study treatment.

The primary endpoint is defined as participants with treatment-emergent adverse events from baseline through Month 12. The registry record does not include a posted inferential analysis of that endpoint or clarify in the safety entries the period represented by each listed count. The counts should therefore be read as descriptive registry safety figures, not as a comparison with another group or proof that an event cannot occur. Zero recorded serious events and zero deaths are observations in this study group; they do not establish that the underlying risk is zero. The record does not report uncertainty intervals for these counts.

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

The results recorded for this extension describe safety experience in a small, single-group cohort: the registry lists 13 participants at risk, with 0 participants recorded with serious adverse events, 11 with other adverse events, and 0 deaths. These entries are descriptive. They do not show how the same participants would have fared under a control condition, and they do not quantify a treatment effect relative to another intervention.

The distinction between what the study set out to examine and what the registry posts is important. The study description includes safety and efficacy aims and lists functional and cardiac outcomes at later visits. However, no analyses are listed, and numerical results for those secondary outcomes are not reported in the registry record. The outcome descriptions alone do not establish improvement, worsening, stability, or a treatment-related change.

In general, an observed event count is not the same as a precise estimate of the event frequency in a broader population. Precision depends on the amount of information and the analysis used; no uncertainty interval is posted. The open-label, uncontrolled extension design also limits causal interpretation, since observed outcomes cannot be separated from the natural course of the condition, selection into the extension, or other influences using a concurrent comparison.

The entries therefore support a narrow conclusion about what the registry records for this study group, not a conclusion about treatment effectiveness or safety in other populations. They do not establish that an event is impossible, that treatment caused an event, or that treatment prevented one. Further interpretation would require fuller outcome results, participant follow-up information, and analysis details, none of which are reported in the registry record.

14. Why This Trial Matters Statistically

Extension studies address follow-up beyond the initial period of a preceding trial. This record describes continued deramiocel exposure among participants who completed 12 months of follow-up in HOPE-2, with assessments planned through Month 60 and possible continued treatment in a long-term open-label extension. Such follow-up can be relevant for describing longer-term exposure and outcomes, particularly when the registered outcomes include repeated safety, functional, and cardiac assessments.

Statistically, however, extended observation does not by itself create a controlled comparison. Participants entering an extension have already passed through earlier study participation and may be a selected subset. With a single group and no masking, the observations are useful as descriptive records but cannot isolate the effect of treatment from other explanations. This distinction matters when readers interpret event counts or later-visit measures.

The record also illustrates why a detailed outcome schedule should not be mistaken for a reported analysis. It names several outcome domains and visits, but lists no analyses or numerical results for efficacy measures. The registry does report selected safety counts, yet those figures are not accompanied by uncertainty estimates or event-level detail. The design and reporting information therefore set clear limits on what can be inferred.

For biostatistical interpretation, the key contribution is a description of the study structure and its reporting boundaries: an open-label, single-group extension, a participant-count safety endpoint, and descriptive safety entries. Recognizing those boundaries helps prevent unsupported comparisons and keeps the distinction clear between planned assessments and results actually reported.

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 study has no concurrent control group and is not randomized, so the registry record cannot support a like-for-like comparison of outcomes. Its open-label design also means treatment is not masked. These features limit causal conclusions from observed safety counts or changes over time. The record describes participants as having completed 12 months of follow-up in HOPE-2 before entering the extension, so the enrolled group may not represent all people with Duchenne Muscular Dystrophy or everyone who began HOPE-2.

Enrollment was 13, and the posted safety counts have no reported confidence intervals or inferential analyses. The registry lists 0 participants with serious adverse events, 11 with other adverse events, and 0 deaths, but it does not provide event-level descriptions, timing, attribution, or a breakdown of the other adverse events. The period represented by each safety count is not specified alongside those entries. Thus, their relationship to the primary endpoint’s baseline-through-Month-12 window cannot be established from the posted details alone.

The registry lists functional and cardiac outcomes at later visits but does not report numerical results or analyses for them. It also does not report how many participants completed each visit, how missing measurements were handled, or which analysis populations were used for those outcomes. The statistical analysis plan, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record. These gaps prevent assessment of the precision, robustness, or potential influence of missing data on longitudinal findings. The study’s planned duration and visit schedule do not establish actual treatment exposure or completed follow-up.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-label Extension of the HOPE-2 Trial — NCT04428476.
• Registry record last updated 2026-09-22; status last verified 2026-07.
• Results first posted 2025-02-24.
• 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

NCT04428476 is a Phase 2, multicenter, open-label extension of the HOPE-2 Duchenne Muscular Dystrophy trial, sponsored by Capricor Inc. It is a single-group study with no masking and enrollment of 13 participants who completed 12 months of follow-up in HOPE-2. The intervention is intravenous deramiocel (CAP-1002), described as 150 million Cardiosphere-Derived Cells per infusion every 3 months.

The primary endpoint is the number of participants with treatment-emergent adverse events from baseline through Month 12. The registry’s safety entries list 0 participants with serious adverse events among 13 at risk, 11 with other adverse events among 13 at risk, and 0 deaths. No analyses are listed. Numerical results for the listed upper-limb and cardiac outcomes are not reported in the registry record, nor are the statistical analysis plan, missing-data methods, or sample-size justification. The study is active, not recruiting.