Extension Study to Study PQ-110-001 (NCT03140969): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Study to Study PQ-110-001 (NCT03140969) (NCT03913130), a na phase 1, phase 2 study. The primary outcome is Frequency of Ocular AEs.

2. Clinical Question

3. Trial Design

This was an open-label extension study of QR-110, listed as phase 1 and phase 2. Its official title describes evaluation of safety, tolerability, efficacy, and pharmacokinetics in subjects with Leber congenital amaurosis associated with the specified CEP290 mutation. The record lists a single-group model, no masking, and allocation as not applicable. These features mean that the study was not designed as a blinded, randomized comparison between treatment groups.

The extension was intended for subjects who completed study PQ-110-001. The brief summary says they could be given the opportunity to enroll for continued dosing if available data supported current and/or future benefits for the subject. This describes a selected extension population rather than an unselected group of all people with the condition. The registry record does not report how many people were eligible, how many were invited, or how many declined participation.

Nine participants enrolled. The first treated eye was assigned maintenance dosing every 6 months, while the contralateral eye received a loading dose followed by maintenance dosing every 6 months; both regimens used intravitreal administration. The record does not report dose amounts, adherence, interruptions, or the number of participants who received treatment in both eyes throughout follow-up.

The listed primary endpoint was frequency of ocular adverse events over 24 months, expressed as participants. Secondary outcomes include changes in best-corrected visual acuity in the first treated eye, mobility course score, photoreceptor outer segment layer thickness, OCI, blue and red full-field stimulus testing, VFQ-25, and CVAQ. The record lists 14 outcome measures overall. No analyses are reported for these outcomes in the registry record, so the listed measures indicate what was planned or tracked, not evidence of a reported efficacy result.

The study started on 2019-05-13, had a primary completion date of 2022-10-03, and is marked terminated. The reason for termination and whether termination affected follow-up or outcome collection are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

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 Ocular AEs, measured over 24 months.

The primary endpoint is the frequency of ocular adverse events over 24 months. It is defined in terms of participants, so the intended summary is a count of participants experiencing an event rather than a measure of event severity, duration, or change in vision. The registry record does not give the endpoint result or explain how multiple events in one participant would be handled in the endpoint calculation.

Safety endpoints are used to describe unwanted events observed during treatment and follow-up. In general, counting participants with an event can show how widely an event occurred in the study group. It is different from counting every event: one participant can experience more than one event, and a participant count does not show the total number of episodes. A count also does not establish that the treatment caused the event. Attribution, event definitions, timing, and comparison with an appropriate control are relevant to causal interpretation.

The registry record separately lists serious adverse events and other adverse events. Those safety figures should not be treated as the primary ocular endpoint result: the record does not establish in the posted outcome data that the serious-event count is a result for ocular adverse events over the stated 24-month timeframe. The endpoint definition and timeframe are reported, but its analysis population, event-coding rules, and result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study and lists counts of participants with safety events. These are descriptive statistics: they summarize what was recorded among the people enrolled. No inferential analysis of the clinical outcomes is reported in the registry record. Statistical concepts below are general explanations and should not be taken as a description of analyses actually performed for this study.

What does a participant count tell us?

A count of participants with an event answers how many people in the study group were recorded as having at least one event under the relevant definition. It does not count repeated episodes separately. If the aim is to summarize the proportion affected, the count needs to be interpreted alongside the number of participants at risk and the rules for follow-up. A percentage can make a count easier to compare across groups, but it does not remove uncertainty, especially when the group is small. The record gives a percentage for the leading serious-event term, but it does not report a confidence interval for that percentage.

A confidence interval is a range of values generated by a statistical method to express uncertainty around an estimate. In general, a narrower interval indicates greater precision under the assumptions of that method. An interval is not a guarantee that the true value lies in the range, and its interpretation depends on the design and analysis. No confidence interval for the primary endpoint or other clinical outcomes is reported in the registry record.

Why does the single-group design matter?

With one treated group, the direct descriptive question is what happened among participants who received QR-110 in the extension. A treatment comparison requires a credible reference group or another suitable design-based source of comparison. Without a concurrent control group, a change from an earlier measurement could reflect treatment, natural variation, progression, prior treatment, measurement conditions, or other factors. A before-and-after change alone would not isolate the treatment effect.

In a randomized comparison, allocation is intended to make groups comparable on average with respect to factors affecting the outcome. This record lists allocation as not applicable and describes a single group, so that protection against confounding is not available. Open-label conduct also means outcomes that require judgment may be susceptible to expectations or observer effects. These are general design considerations; the registry record does not report a masking procedure or a comparator analysis.

How should the planning calculations be understood?

The sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration considers detecting stated fractions of the observed effect. These are planning assumptions, not evidence that the extension itself had two arms. The trial record identifies a single-group study, so the two-arm allocation assumption in the planning illustration does not describe the observed design.

Sample-size calculations ask how many participants might be needed under specified assumptions to detect an effect with a chosen statistical procedure. Such calculations depend on the assumed effect, variability, outcome type, allocation, significance level, and target power. An illustration based on an observed effect is not a prospective justification for this study's enrollment, and it is not observed power. Observed power is not a substitute for reporting an estimate with its uncertainty. The numerical sample-size outputs and the effect estimate on which the illustration is based are not reported in the registry record.

What do significance tests and multiplicity address?

In general, a significance test assesses how compatible data are with a specified null hypothesis under a statistical model. A p-value does not measure the size or clinical importance of an effect, and it does not state the probability that a hypothesis is true. Because no outcome analyses or p-values are reported in the registry record, no conclusion based on statistical significance can be drawn from the listed endpoints.

When several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. Multiplicity procedures may control a chosen error rate, or investigators may designate one outcome as primary and treat others as supportive or exploratory. Which approach, if any, was specified for this study is not reported in the registry record. The number of listed outcome measures alone does not establish how they were prioritized or analyzed.

What does over-dispersion mean in general?

For count outcomes, a statistical model may assume a particular relationship between the average count and its variability. Over-dispersion means the observed variability is greater than that assumed by a model such as a simple Poisson model. If ignored, standard errors can be too small and confidence intervals or tests can be misleading. This concept is relevant to analyses of event counts, but the primary endpoint is described as participants with an event, and the registry record does not report a count model or any adjustment for over-dispersion.

What can be said about the analysis plan?

The registry record does not report the statistical analysis methods for the primary or secondary outcomes, the analysis populations, handling of missing observations, or any interim analyses. It also does not report model covariates, adjustment procedures, or prespecified sensitivity analyses. Those details cannot be inferred from the endpoint names or from the fact that results are absent. The defensible interpretation is therefore descriptive: the record contains a small set of safety counts and outcome definitions, but not reported outcome analyses from which to assess efficacy, precision, or formal statistical evidence.

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("Drug QR-110")
n      <- c(9)
events <- c(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  Drug QR-110  9  7  77.8  40.0  97.2  45.3  93.7  44.4  93.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 14 outcome measures, including the primary frequency of ocular adverse events and secondary outcomes addressing visual acuity, mobility, retinal structure, stimulus testing, and vision-related questionnaires. It does not report how the secondary outcomes were prioritized, whether a hierarchy was prespecified, or whether any adjustment for multiple comparisons was planned. When several outcomes are assessed, unadjusted tests can increase the chance of a false-positive finding across the family of tests. That general concern does not imply that any false-positive result occurred; no outcome analyses are reported in the registry record.

Missing-data methods are not reported in the registry record. It does not state how missing visits, incomplete outcome measurements, withdrawals, or deaths would be handled in efficacy analyses. The number completing follow-up and the amount of missing data for each outcome are also not reported. Without these details, it is not possible to determine whether an analysis would use available observations, imputation, or another method, or to assess whether missingness could bias an estimate.

The analysis populations are not reported in the registry record. It is therefore not possible to establish whether outcomes were intended to be analyzed in all enrolled participants, only participants meeting specified criteria, or another group. No interim analyses or stopping rules are reported. The study's terminated status alone does not establish why it ended, whether any planned analysis was changed, or how missing observations were treated.

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: lumbar vertebral fracture (11.1%).

The safety record lists nine participants at risk in the QR-110 group. One participant is recorded as affected by a serious adverse event, and eight are recorded as affected by other adverse events. The record lists zero deaths. The leading serious-event term is lumbar vertebral fracture, reported as 11.1%. These figures are counts and a reported percentage for the listed group; they are not a comparison with an untreated group.

A serious adverse event is a classification of seriousness, not a statement that the event was caused by treatment. The registry record does not report the event's relationship to QR-110, timing, duration, outcome, or whether it was ocular. The leading term should not be read as an ocular adverse event merely because the primary endpoint concerns ocular adverse events. The separate primary endpoint result is not reported in the registry record.

Counts of affected participants also do not necessarily equal counts of all event episodes. The record does not provide event-level detail or explain whether an individual could contribute to both serious and other-event categories. These safety observations are useful as descriptive information about the enrolled group, but the small group and absence of a comparator limit conclusions about frequency, causation, and how the observations compare with other populations.

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

The registry record establishes that an extension study of QR-110 enrolled nine participants and collected or planned to collect safety and efficacy outcomes. It reports counts of participants with serious and other adverse events, identifies a leading serious-event term, and lists zero deaths. Those details describe the posted safety information; they do not establish a treatment effect.

The record does not report results for the primary endpoint, frequency of ocular adverse events over 24 months. It also does not report analyses for the listed visual, mobility, retinal, testing, or questionnaire outcomes. As a result, no numerical estimate of change in these measures, no confidence interval, and no statistical comparison can be interpreted from the registry record. Absence of a posted analysis is not evidence that an outcome did or did not change.

The study has no concurrent control group and is open-label. In general, those design features limit causal interpretation: changes over time cannot be attributed to QR-110 alone, and knowledge of treatment may influence assessment or reporting. The extension's participants had completed a preceding study and were offered further enrollment under the conditions described in the summary. The enrolled group may therefore not represent people who did not complete or enter the earlier study.

The serious-event count does not establish that QR-110 caused an event, and the registry record does not report event attribution. Likewise, a count of participants with other adverse events does not reveal the severity, duration, recurrence, or clinical course of each event. These limits matter even when counts are reported clearly: descriptive safety data and causal evidence answer different questions.

The record's terminated status is a study-status designation, not a result. The reason for termination, its timing relative to outcome collection, and its effect on completeness are not reported in the registry record. The findings should therefore be read as a limited description of the participants and information posted, rather than as a complete estimate of safety or efficacy for a broader population.

14. Why This Trial Matters Statistically

Extension studies address a different question from a trial that assigns participants to treatment and control groups. They can describe continued dosing and longer-term observations among people who have already participated in an earlier study. In this case, the registry summary describes an opportunity for subjects completing PQ-110-001 to enter for continued dosing when available data supported current and/or future benefits for the subject. That context is important when interpreting who entered the extension and what the results can represent.

Statistically, a small single-group record illustrates the distinction between observing events and estimating comparative effects. The adverse-event counts convey what was recorded among the enrolled group, while the absence of a concurrent comparator prevents a direct estimate of how those counts differ from what would have occurred without QR-110. A count can be informative as a description and still leave substantial uncertainty about general frequency and causation.

The endpoints span several domains: ocular safety, visual acuity, mobility, retinal structure, visual function testing, and questionnaires. This breadth can be useful for mapping what investigators intended to monitor. At the same time, multiple outcomes require transparent priorities, analysis methods, and missing-data handling for readers to judge the strength and precision of findings. Those details and outcome analyses are not reported in the registry record.

The record also demonstrates why registration status and outcome reporting should be read separately. The study is marked terminated and includes study dates, but the reason for termination and the fate of planned analyses are not reported. A registered endpoint is not itself a result, and an enrollment count is not evidence of adequate precision. Clear distinction among design, observed safety counts, and unreported efficacy analyses prevents stronger conclusions than the record supports.

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.

Enrollment was nine, and the study had a single group with no concurrent control. The safety counts therefore describe a limited treated cohort and cannot support a direct treatment-versus-control comparison. The record does not report participant characteristics beyond the condition and mutation named in the study description, limiting assessment of how closely the enrolled group may resemble other populations.

The extension was intended for subjects completing the preceding study, with an opportunity to enroll described as conditional on available data supporting current and/or future benefits for the subject. The numbers eligible, invited, declining, or not entering are not reported in the registry record. Selection into the preceding study and extension may limit how broadly observations can be generalized.

The study was open-label. The registry record does not report masking for outcome assessment or details of event adjudication. The primary endpoint timeframe is 24 months, but participant-level follow-up and completion are not reported. The reason for termination and whether it affected outcome collection are also not reported in the registry record.

No primary or secondary outcome analyses are reported. Statistical methods, analysis populations, missing-data procedures, multiplicity handling, and interim analyses are not reported in the registry record. These omissions prevent assessment of estimated efficacy, precision, robustness, and the impact of incomplete observations. The reported safety counts do not include enough event-level information to evaluate timing, recurrence, severity beyond the serious classification, ocular status, or causal attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Extension Study to Study PQ-110-001 (NCT03140969) — NCT03913130.
• Registry record last updated 2024-10-15; status last verified 2024-10.
• Results first posted 2023-01-04.
• 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

NCT03913130 is an open-label, single-group extension study of QR-110 in subjects with Leber congenital amaurosis associated with the c.2991+1655A>G mutation in CEP290. It is listed as phase 1 and phase 2, enrolled nine participants, and is marked terminated. The study started on 2019-05-13, with primary completion dated 2022-10-03.

The primary endpoint was frequency of ocular adverse events over 24 months. Listed secondary outcomes cover visual acuity, mobility, retinal structure, stimulus testing, and vision-related questionnaires. No analyses are reported for the outcomes in the registry record.

Safety information lists one participant with a serious adverse event, eight with other adverse events, and zero deaths. Lumbar vertebral fracture is the leading serious-event term, reported as 11.1%. The record does not report causal attribution or a comparator. The reason for termination, analysis methods, missing-data procedures, and participant-level follow-up are not reported in the registry record.