Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ENPP1 Deficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ENPP1 Deficiency (NCT04686175), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Dose Evaluation Period.

2. Clinical Question

3. Trial Design

NCT04686175 is a completed Phase 1/2 study titled “Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ENPP1 Deficiency.” Its official title describes a multiple ascending dose study followed by an open-label long-term extension. The registry gives the study design as single-group, with no masking and allocation not applicable. Consequently, the reported outcomes are observations among participants treated with INZ-701, not a randomized estimate against a concurrent comparator.

The study began on 2021-11-21 and reached primary completion on 2024-10-29. The registry status is completed, with enrollment of 13. Its stated aims include assessing safety, tolerability, pharmacokinetics, and pharmacodynamics, and identifying a dose regimen for further clinical development. The primary endpoint discussed in the registry is the number of participants with treatment-emergent adverse events during the Dose Evaluation Period, whose timeframe is 32 days.

The Dose Evaluation Period is described as a multiple ascending dose 3 + 3 cohort design. The arm description gives planned initial doses of 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg with a twice-weekly regimen for cohorts 1–3, and 1.2 mg/kg once weekly. The dose assigned to each cohort beyond those details, the dose actually received by each participant, and any changes to the planned regimen are not reported in the registry record. The long-term extension is named in the official title, but its detailed design and outcome results are not included in the record information summarized for these safety findings.

The registry lists nine outcome measures and no analyses. This means the posted information supports a descriptive account of recorded outcomes, but it does not provide a reported inferential analysis for estimating a treatment effect. The cohort counts should be read as safety observations within an early-phase, open-label study rather than as evidence from a controlled efficacy 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.

Period 1: Dose Evaluation Period

Period 2: Open-label Extension Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population included all participants who received at least one dose of study treatment during the respective study 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.

Population: The baseline analysis population included all 13 participants who received study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Dose Evaluation Period, measured over 32 days.

The primary endpoint is the number of participants with treatment-emergent adverse events during the Dose Evaluation Period. The registry defines treatment-emergent adverse events as any adverse event occurring from the first dose of INZ-701 through 30 days after the last dose. The stated timeframe is 32 days. The analysis population includes participants who received at least one dose of study treatment during the relevant study period.

A participant count is a binary-outcome summary: each participant is classified according to whether an event meeting the endpoint definition occurred during the specified period. Such an endpoint can give a direct descriptive account of how many treated participants had an event, without implying how many separate episodes occurred or how severe every event was. The primary endpoint as named does not itself distinguish serious from non-serious events; the registry reports serious adverse-event information separately by cohort.

Safety endpoints are used in early-phase dose evaluation because observing adverse events and their timing is part of characterizing tolerability during exposure. They can help describe the types of events recorded and whether serious events occurred in the study population. Their interpretation depends on the event definition, observation window, number of participants exposed, and completeness of recording.

The registry record does not report a separate aggregate result for the named primary endpoint in the information available for this analysis. The cohort-level serious adverse-event counts therefore should not be treated as a substitute for an overall count of all treatment-emergent adverse events. Nor does a count alone establish that treatment caused an event: causal attribution requires interpretation beyond whether an event occurred after treatment began.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting a safety result begins with identifying the population, event definition, and observation window. The primary endpoint counts participants with treatment-emergent adverse events, rather than counting every event episode. An event qualifies by its timing: it must occur from the first dose through 30 days after the last dose. The registry gives the Dose Evaluation Period timeframe as 32 days. This definition standardizes which events enter the endpoint, but it does not by itself establish that treatment caused them.

What does a participant count represent?

For a binary endpoint, each participant is considered to have either experienced an event meeting the definition or not. A count can be useful for a direct description of how many people had an event in the observed group. It is not the same as a count of all event episodes: a participant with several events may still contribute as one participant to a participant-based endpoint. The registry’s primary endpoint is explicitly a participant count. Separate serious adverse-event counts are also reported by cohort, while the serious adverse-event terms are listed with percentages.

Counts require context. The number of participants at risk describes the group in which events could be observed, while the number affected describes participants recorded with the specified outcome. Here, the registry reports those quantities by cohort for serious adverse events. The cohort counts should be retained as counts rather than treated as a precise measure of comparative risk. No confidence intervals or formal comparison results are reported alongside them.

Why does the study design matter?

The record describes a single-group, open-label study with allocation not applicable and masking none. In a randomized controlled comparison, a concurrent comparator can help distinguish treatment-group differences from changes or events that might have occurred without the study treatment. This study has no such comparison. Therefore, cohort-to-cohort differences are descriptive and cannot support a causal contrast between INZ-701 and a control treatment.

Open-label means the registry does not describe masking of treatment. General statistical principle: knowledge of treatment can affect how symptoms are reported, how events are assessed, or how decisions are made about documenting an event. This possibility does not mean that any particular event was misclassified; it is a consideration when interpreting unmasked safety data. The registry does not report independent blinded event adjudication.

The 3 + 3 dose-cohort description and multiple ascending dose plan provide context for the study’s early-phase purpose. But the actual participant-level dose exposure and the complete dose assignment by cohort are not reported in the registry record. Without those details, cohort counts should not be used to infer that a particular dose produced a particular safety profile. The reported counts do not constitute a dose-response analysis.

What can an inferential analysis add?

Inferential methods can quantify uncertainty around an observed estimate or test a specified comparison. A confidence interval is a range that, under the method’s assumptions, indicates the precision of an estimate; narrower intervals generally indicate greater precision. A p-value summarizes how compatible data are with a specified null model, assuming that model and the analysis assumptions are appropriate. Neither measure demonstrates that an observed event was caused by treatment. The registry record reports no confidence intervals, p-values, or analyses for the outcomes, so no such inferential conclusion can be drawn from the posted information.

General statistical principle: a small number of observations commonly yields limited precision, especially when outcomes are divided across cohorts. Even when a count is exact for the observed participants, it does not pin down the frequency that might be seen in a broader population. The study enrollment of 13 and the cohort sizes reported for serious adverse events make the descriptive nature of these figures particularly important. No unreported population rate should be inferred from a cohort count alone.

How should percentages and event terms be read?

The registry lists patella fracture at 33.3%, procedure aborted at 33.3%, and syncope at 25.0% among the serious adverse-event terms. The denominator and calculation basis for these percentages are not reported in the registry record. It is therefore not possible to tell from the record whether each percentage refers to participants, events, a cohort, or another denominator. The percentages should be quoted as listed, without translating them into counts or combining them.

General statistical principle: over-dispersion occurs when variability in count data is greater than a chosen model expects. In such settings, a model that assumes too little variability can make uncertainty appear smaller than it is. No count model or over-dispersion assessment is reported for this study; this concept is relevant only as a general consideration when analyzing event counts, not as a finding about these data.

What do planning illustrations mean?

Any sample-size planning illustration based on an observed effect is hypothetical, not an observed trial result and not a measure of the study’s achieved power. General statistical principle: a planning calculation describes the sample size that assumptions might require for a specified future comparison. It depends on the assumed effect, significance level, allocation, and analysis method. It cannot repair the absence of a randomized comparator or turn an early-phase cohort observation into a comparative estimate. The registry does not report a sample-size justification or the assumptions used to design this trial, so its original planning rationale is not reported in the registry record.

The registry lists nine outcome measures and no analyses. It does not report the statistical analysis plan, interim analyses, multiplicity procedure, or detailed handling of missing outcome data. Accordingly, interpretation should stay close to the endpoint definitions and the observed counts, and should not imply that an unreported model or adjustment was performed.

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("Cohort 1: Dose Level #1", "Cohort 2: Dose Level #2", "Cohort 3: Dose Level #3", "Cohort 4: Dose Level #4")
n      <- c(3, 3, 3, 4)
events <- c(0, 1, 0, 3)
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  Cohort 1: Dose Level #1  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 2: Dose Level #2  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6
ARM  Cohort 3: Dose Level #3  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 4: Dose Level #4  4  3  75.0  19.4  99.4  30.1  95.4  28.4  94.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, but the statistical analysis plan is not reported in the registry record. The multiplicity strategy, if any, is not reported in the registry record. Multiplicity matters when several outcomes or comparisons are evaluated: general statistical principle, looking across multiple tests can increase the chance of finding at least one apparently noteworthy result by chance. Without a reported analysis plan and adjustment strategy, there is no basis for describing the reported safety figures as multiplicity-adjusted or for inferring how outcome priority was handled beyond the endpoint identified as primary.

The registry record does not report interim analyses. It also does not describe how missing observations were handled, whether any outcome data were missing, or whether participants withdrew during the Dose Evaluation Period. These details matter because incomplete follow-up can affect which events are observed and the interpretation of the denominator. The stated primary-outcome population includes participants who received at least one dose during the relevant period, but the record does not provide further detail on exclusions or missing data for the outcome.

The endpoint timeframe and event definition are stated, which helps identify the intended observation window. However, the record information does not provide an aggregate result for the primary endpoint or a detailed analysis population count for that endpoint. There are no reported confidence intervals or inferential analyses. Conclusions should therefore remain descriptive: the serious adverse-event counts characterize the cohorts as recorded, but the registry does not support claims about statistical significance, adjusted comparisons, or the impact of missing data.

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: patella fracture (33.3%), procedure aborted (33.3%), syncope (25.0%).

The registry reports serious adverse events by dose cohort as participants at risk and participants affected. In Cohort 1, 0 of 3 participants were listed as affected; in Cohort 2, 2 of 3; in Cohort 3, 0 of 3; and in Cohort 4, 1 of 4. The registry lists 0 deaths in each cohort. These are cohort-level participant counts, not a comparison against an untreated or active-control group.

The serious adverse-event terms listed are patella fracture at 33.3%, procedure aborted at 33.3%, and syncope at 25.0%. The registry record does not state the denominator or calculation basis for these percentages. They should not be converted into event counts or treated as cohort-specific rates without that information. A term percentage may describe event reporting differently from the participant counts by cohort.

Serious adverse events are a subset of safety information, not the same outcome as all treatment-emergent adverse events. The primary endpoint covers any adverse event meeting its timing definition during the 32-day period, while the serious-event figures report only serious events. The record does not give an aggregate result for the primary endpoint. These observations describe events recorded during the study; they do not establish causation or comparative safety.

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

The findings mean that the registry records serious adverse events in some participants in certain cohorts during this open-label study, and no deaths in any of the reported cohorts. They also include three serious adverse-event terms with registry-listed percentages. These observations are useful as a descriptive account of what was recorded among participants exposed to INZ-701. They do not, on their own, determine whether an event was caused by treatment.

The study is single-group and has no concurrent control. Thus, there is no randomized comparison to estimate how event experience differed from a comparable group without INZ-701 or receiving another intervention. Cohort differences should not be interpreted as treatment effects, because the record does not describe randomized allocation across dose cohorts and does not provide complete participant-level dose exposure details. The small enrollment of 13 also limits how precisely the cohort experience can characterize a broader population.

The primary endpoint is intended to count participants with any treatment-emergent adverse event over a defined period, but an aggregate result for that endpoint is not reported in the registry record. Serious adverse-event counts are narrower and cannot stand in for all events included in the primary definition. The record also does not provide confidence intervals, p-values, or an inferential analysis for the reported results. Accordingly, claims about statistical significance or precise event frequencies in a wider population are not supported by the posted data.

The study’s title and stated aims include efficacy, pharmacokinetics, pharmacodynamics, safety, and tolerability. The safety results do not establish efficacy, a clinical benefit, or a comparative advantage. Nor do they establish that treatment lacks an effect. They describe the scope of the posted safety observations and the limits of what can be concluded from them. The record identifies dose-regimen selection for further development as a study goal; it does not report a conclusion on which regimen should be selected.

14. Why This Trial Matters Statistically

This study is statistically important because it illustrates the role of early-phase evidence: describing safety and tolerability while evaluating escalating dose regimens, rather than estimating a controlled treatment effect. The registry’s stated purpose includes identifying a dose regimen for further clinical development. For that purpose, cohort-level observations can contribute information about events recorded during exposure, but their interpretation depends on careful attention to denominators, event definitions, follow-up, and uncertainty.

The primary endpoint is clearly defined in timing and unit: it counts participants with treatment-emergent adverse events during a 32-day Dose Evaluation Period, with events eligible from the first dose through 30 days after the last dose. This specificity helps readers understand what the endpoint is intended to capture. At the same time, the lack of an aggregate primary-endpoint result in the registry information available for this analysis means that the main endpoint cannot be quantitatively summarized from the posted data. The serious adverse-event counts answer a narrower question.

The study also demonstrates why a count should not be mistaken for a comparative conclusion. With a single group and no masking, recorded safety outcomes are descriptive. The fact that serious adverse events appear in some cohorts and not others does not establish that cohort dose caused a difference, particularly when complete dose assignments are not reported and participant numbers are limited. A larger controlled study with prespecified analyses could address different questions, but its details or results are not reported in this record.

Finally, the registry’s limits are themselves statistically relevant. No analyses are listed, and the analysis plan, multiplicity handling, missing-data approach, and interim analyses are not reported. Readers can assess the definitions and reported cohort counts, but cannot verify an inferential framework or precision estimates from the registry record. Keeping descriptive safety observations separate from causal and efficacy claims is essential for interpreting this early-phase evidence.

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 main limitation is the absence of a concurrent control group. The registry describes a single-group, open-label design, so the reported outcomes cannot estimate a comparative effect or separate treatment-associated events from other causes. Allocation is listed as not applicable and masking as none. The study therefore does not provide a randomized, blinded contrast for interpreting safety or efficacy.

Enrollment was 13, and the serious adverse-event counts are reported within small cohorts. Counts from groups of this size are descriptive and provide limited information about how often events might occur in a broader population. The registry does not report confidence intervals or other estimates of uncertainty. In addition, the percentages attached to serious adverse-event terms have no reported denominator or calculation basis, limiting their interpretation.

The named primary endpoint is not accompanied by an aggregate result in the registry information summarized for this analysis. The serious adverse-event results do not cover every event in the primary endpoint definition. The actual doses received by participants and full dose assignment by cohort are not reported in the registry record, so dose-specific interpretation is limited.

The record does not report a statistical analysis plan, interim analyses, multiplicity procedures, or missing-data methods. It also does not describe whether outcome data were missing or how participant withdrawals were handled. The long-term extension is identified in the official title, but its detailed design and results are not included in the safety information. These omissions constrain assessment of endpoint completeness, analysis choices, and longer-term safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ENPP1 Deficiency — NCT04686175.
• Registry record last updated 2026-10-27; status last verified 2026-10.
• Results first posted 2026-10-27.
• 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

NCT04686175 is a completed Phase 1/2, open-label, single-group study of INZ-701 in adults with ENPP1 deficiency. The record lists enrollment of 13, no masking, and allocation as not applicable. The study began on 2021-11-21 and reached primary completion on 2024-10-29.

The primary endpoint is the number of participants with treatment-emergent adverse events during the 32-day Dose Evaluation Period. Serious adverse-event participant counts are reported by dose cohort, along with three serious adverse-event terms and percentages. The registry lists 0 deaths in each cohort. It does not report an aggregate result for the named primary endpoint in the information analyzed here, and the denominator for the serious-event term percentages is not stated.

The record lists nine outcome measures and no analyses. It does not report the statistical analysis plan, multiplicity approach, missing-data methods, interim analyses, or a sample-size justification. The posted data support a descriptive reading of the recorded safety observations, not a randomized comparison or a causal conclusion.