This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease (NCT04553406), a randomized phase 2 study. The primary outcome is Maximum Plasma Concentration (Cmax) of SPR719.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04553406 |
| Phase | Phase 2 |
| Condition | Mycobacterium Avium Complex, Non-tuberculous Mycobacterium Pulmonary Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Spero Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with Mycobacterium avium complex (MAC) pulmonary disease, within the broader category of nontuberculous mycobacteria pulmonary disease. The registry reports an enrollment of 2. It also states that no participants were enrolled at study sites conducting intensive pharmacokinetic evaluations, so the primary endpoint's planned assessment population was absent.
Intervention
The active intervention was oral SPR720, a prodrug that generates SPR719, the active moiety. The two described dose regimens were SPR720 500 mg once daily and SPR720 1000 mg once daily, each for 28 days. The study's central pharmacokinetic question concerned the plasma concentration of SPR719 after SPR720 administration. Safety, tolerability, and efficacy were also part of the broader study purpose.
Comparator
The registry describes placebo and open-label Standard of Care (SOC) as comparator interventions. Placebo was administered orally once daily for 28 days. SOC was a regimen selected at the investigator's discretion. The record does not report enough outcome analyses to establish how these comparators were used in statistical comparisons or to characterize comparative effects.
Primary question
The primary endpoint was the maximum plasma concentration (Cmax) of SPR719, assessed on Day 1 and Day 28, before dosing and at scheduled post-dose times. This endpoint asks how high plasma SPR719 concentration reaches during the specified sampling period. Because no participants enrolled at intensive PK sites, the registry does not report Cmax results. The record therefore cannot answer the primary pharmacokinetic question or support a comparison of Cmax across treatment groups.
3. Trial Design
The registry describes a randomized, partially blinded, placebo- and comparator-controlled, multicenter, phase 2a, dose-ranging, proof-of-concept study. Its official title also identifies safety, tolerability, pharmacokinetics, and efficacy as areas of evaluation. The design is recorded as parallel, with quadruple masking. These descriptions appear alongside an open-label SOC intervention; the record does not explain which study roles were masked or how masking applied to SOC.
SPR720 was assigned in two described oral regimens: 500 mg once daily for 28 days or 1000 mg once daily for 28 days. Placebo was also administered orally once daily for 28 days. The SOC regimen was at the investigator's discretion. The registry records randomized allocation, but the allocation procedure and concealment details are not reported in the registry record.
The recorded study start was 2020-12-03, and primary completion was 2021-01-28. The status is terminated. The reason for termination, any planned follow-up beyond treatment, and whether the study stopped according to its original schedule are not reported in the registry record. The registry lists enrollment as 2, while also noting that no participants were enrolled at the sites intended for intensive PK evaluation. Consequently, the planned primary endpoint lacks observations, and the record does not offer a basis for interpreting efficacy or safety as comparative treatment effects.
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
| Stage | SPR720 500 mg | Placebo |
|---|---|---|
| STARTED | 1 | 1 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | SPR720 500 mg | Placebo |
|---|---|---|
| Study Discontinuation | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: No participants were enrolled at study sites that were conducting intensive PK evaluations.
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.
| Characteristic | Unit | SPR720 500 mg | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 1 | 2 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 1 | 1 |
| Age, Categorical: >=65 years | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: White | Participants | 1 | 1 | 2 |
| Region of Enrollment: United States | participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Plasma Concentration (Cmax) of SPR719, measured over Day 1 and Day 28 pre-dose and 1, 2, 4, 8, 12, and 24 hours post-dose.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is maximum plasma concentration, or Cmax, of SPR719. SPR720 is described as a prodrug, and SPR719 as its active moiety. Cmax captures the highest measured plasma concentration over a specified sampling period. In pharmacokinetic studies, it is used to characterize systemic exposure to a drug-related active substance and can help describe how exposure varies across dose regimens. It is an exposure measure, not a direct measure of clinical benefit.
Blood samples were planned on Day 1 and Day 28, before dosing and at 1, 2, 4, 8, 12, and 24 hours after dosing. The description says intensive PK evaluation was to occur at a subset of study sites. The registry reports that no participants were enrolled at those sites. Thus, although the endpoint and sampling schedule are specified, Cmax observations and a statistical summary are not reported in the registry record. The unit and analysis parameter beyond the named Cmax endpoint are also not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The key result is the absence of primary pharmacokinetic observations, rather than an estimate of SPR719 exposure. The registry identifies Cmax as the primary endpoint and specifies intensive blood sampling, but states that no participants were enrolled at the sites conducting those assessments. No Cmax value, variability estimate, confidence interval, or treatment-group comparison is reported. Therefore, the primary endpoint cannot be interpreted as evidence for or against a difference in plasma exposure.
The record describes enrollment of 2 and a terminated status. Those details establish that the registry records a small enrollment and that the study did not continue to its planned completion status. They do not explain why it was terminated, whether the enrolled participants completed treatment, or whether outcome data were collected for all listed objectives. The reason for termination and participant-level disposition are not reported in the registry record.
The posted safety counts are limited. For SPR720 500 mg and placebo, the registry lists 1 participant at risk for serious adverse events in each group and 0 affected in each. It also lists 1 participant at risk for other adverse events in each group and 1 affected in each. These counts are descriptive and provide no stable basis for estimating comparative safety. No serious adverse event terms are listed. The registry does not state whether the other adverse events were considered related to treatment, how severe they were, or when they occurred.
The study title includes efficacy, but no efficacy result or statistical analysis is reported. The registry lists 12 outcome measures and 0 analyses. This distinction matters: outcome measures describe what was intended for assessment, while analyses would provide results and their statistical interpretation. The record does not report estimates of treatment effects, measures of uncertainty, or tests comparing groups. A result cannot be inferred from the study's proof-of-concept label or from its planned design.
Overall, the record documents the intended trial framework and a limited set of safety counts, but it does not furnish the primary PK data or comparative efficacy analyses needed to answer the main clinical and pharmacological questions. The absence of reported estimates is not evidence that groups were equivalent, and it is not evidence that an intervention had or lacked an effect.
9. Statistical Methods Explained
Randomization is a design method for assigning participants to study groups using a chance-based process. In general, it is intended to reduce systematic differences between groups at the point of assignment. The registry records randomized allocation and a parallel model, meaning that participants were assigned to a study group and followed under that group rather than being described as switching among treatments. The actual randomization procedure, allocation concealment, and balance of prognostic characteristics are not reported in the registry record. With enrollment recorded as 2, the record does not support reliable estimation of between-group differences even if outcomes had been available.
What does the primary pharmacokinetic endpoint measure?
Cmax is the maximum observed plasma concentration for the analyte and sampling period being studied. Here, the analyte is SPR719, described as the active moiety generated from the SPR720 prodrug. Pharmacokinetic endpoints help characterize exposure; they do not directly establish a clinical effect. The planned schedule covered measurements before dosing and at 1, 2, 4, 8, 12, and 24 hours after dosing on Day 1 and Day 28. The registry says these intensive assessments were planned at a subset of sites, but no participants enrolled at those sites. As a result, no Cmax estimate can be calculated from the reported record.
Why are estimates and uncertainty important?
A treatment-effect estimate describes the observed difference or pattern in outcomes between groups. A confidence interval, in general, expresses the statistical uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies within a particular interval. When estimates and confidence intervals are reported together, readers can assess both the direction and the precision of the results. The registry does not report primary endpoint estimates, confidence intervals, or group-comparison tests. Without those results, neither the size nor the precision of a possible pharmacokinetic or clinical effect can be assessed.
What can the adverse-event counts show?
Adverse-event counts describe how many participants in a group experienced an event under the categories recorded. Counts are not the same as an estimate of comparative risk, especially when the number of participants is very limited. A difference between small group counts can arise by chance and does not, on its own, establish a treatment-related pattern. Serious and other adverse events are separate registry categories; the record lists zero serious events and one participant with an other adverse event in each of the SPR720 500 mg and placebo groups. Event descriptions, severity, timing, and attribution are not reported in the registry record. A statistical comparison or an adjusted safety analysis is also not reported.
What does the record say about the analysis plan?
The registry lists 12 outcome measures and 0 analyses. The primary endpoint is named, and several secondary outcomes concern treatment-emergent adverse events, examination findings, concomitant medication, laboratory tests, vital signs, and electrocardiogram findings. Naming outcomes does not show that they were analyzed or reported. The statistical methods, analysis populations, handling of repeated measurements, covariate adjustment, and approach to missing data are not reported in the registry record.
Multiplicity refers, in general, to the increased chance of obtaining apparently notable results when many outcomes or hypotheses are tested. A prespecified strategy may control that issue, for example by defining a primary comparison or adjusting inference across tests. The record does not report whether any multiplicity strategy was planned or used. The absence of analyses means readers cannot assess how testing across the listed outcomes was handled.
Over-dispersion is a general concern when count data vary more than an assumed statistical model expects. It can make standard errors too small if the model fails to account for that extra variation. No count-model analysis is reported for this study, and the registry does not provide enough outcome data to assess whether over-dispersion was relevant. Likewise, no sample-size justification, interim analysis plan, or detailed statistical analysis plan is reported in the registry record. No power calculation should be inferred from the enrollment or from the absence of results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 12 outcome measures, including the primary SPR719 Cmax endpoint and secondary safety, laboratory, vital-sign, medication-use, examination, and electrocardiogram outcomes. It records 0 analyses. The listed outcomes indicate areas intended for assessment; they do not establish that every measure was collected, analyzed, or reported.
Multiplicity arises in general when several hypotheses or outcomes are examined, because repeated testing can make chance findings more likely. A statistical plan can specify which comparisons are primary, whether secondary analyses are exploratory, and whether any adjustment is used. Such a plan, including any multiplicity procedure, is not reported in the registry record. No inferential results are available to determine how multiplicity might have affected interpretation.
The record does not report analysis populations, including the definition of any intention-to-treat, per-protocol, or safety population. Participant flow, treatment adherence, endpoint evaluability, and reasons for missing observations are also not reported in the registry record. The primary PK description explicitly states that no participants enrolled at intensive PK sites; it does not give Cmax results for another population. Details on imputation, exclusion of incomplete measurements, or sensitivity analyses are not reported.
Accordingly, readers cannot assess whether missing data were related to treatment, outcome status, or study termination. Nor can they judge whether reported results, if any, would apply to all randomized participants or only to a selected analysis group. These are uncertainties about reporting and analysis, not evidence that a particular missing-data method was used.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| SPR720 500 mg | 0 | 1 | 0.0% |
| Placebo | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| SPR720 500 mg | 0 of 1 |
| Placebo | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| SPR720 500 mg | 1 of 1 |
| Placebo | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | SPR720 500 mg | Placebo |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 1 of 1 | 1 of 1 |
| Diarrhea | Gastrointestinal disorders | 1 of 1 | 0 of 1 |
| Vomiting | Gastrointestinal disorders | 1 of 1 | 0 of 1 |
For the SPR720 500 mg group, the registry lists 1 participant at risk for serious adverse events and 0 with a serious event. For placebo, it likewise lists 1 participant at risk and 0 with a serious event. The record lists 1 participant at risk for other adverse events in each group, with 1 affected in each. No serious adverse event terms are listed.
These are sparse descriptive counts, not precise estimates of comparative safety. The record does not report event names for the other adverse events, their severity or timing, or whether investigators considered them related to study treatment. The figures do not cover the SPR720 1000 mg or SOC groups in the adverse-event summary, so they should not be generalized to those interventions. The registry's limited counts cannot establish the presence or absence of less common harms.
12. What the Result Does, and Does Not, Mean
The record does establish that a randomized phase 2a study of SPR720 was undertaken for MAC pulmonary disease, with planned assessment of pharmacokinetics, safety, tolerability, and efficacy. It names Cmax of SPR719 as the primary endpoint and describes the planned sampling schedule. It also records the intervention regimens, comparator options, enrollment, study dates, and terminated status. These details explain the intended research question and the structure of the study.
What the record does not establish is the primary pharmacokinetic result. No participants enrolled at intensive PK sites, and no Cmax estimates are reported. The record also does not provide efficacy comparisons, confidence intervals, or statistical tests. Therefore, it cannot show whether SPR720 changed SPR719 exposure relative to another group, or whether any treatment group differed on clinical outcomes.
The safety counts are limited to the groups and categories recorded and should be read as descriptive observations. They do not permit reliable comparisons or conclusions about treatment-related risk. The absence of listed serious events in the reported groups does not establish that serious harms cannot occur, while the reported other adverse events do not by themselves establish causation.
More broadly, no result should be inferred from the study's phase, proof-of-concept label, randomization, or planned endpoints. A study can be designed to answer a question yet lack the observations and analyses needed to answer it. The registry record documents that gap. Its missing outcome estimates are not evidence of no effect, equivalence, or a favorable effect; the relevant comparative results are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a prespecified endpoint and an estimable endpoint. Cmax of SPR719 was clearly named, and a detailed sampling schedule was specified. Yet the registry states that no participants enrolled at sites conducting intensive PK evaluation. Without the planned measurements, there is no primary endpoint estimate to interpret. A well-defined endpoint alone cannot substitute for observations.
The record also shows why trial labels and design features must be separated from evidence. Randomization and masking can support credible comparisons when data are collected and analyzed appropriately, but they do not guarantee that those comparisons can be made. The study is recorded as randomized and quadruple-masked, while the official title says partially blinded and the SOC intervention is open-label. The record does not explain how these masking descriptions were implemented. This uncertainty affects assessment of the design but does not generate outcome evidence.
Enrollment of 2 and the terminated status place the sparse adverse-event counts in context. With very limited information, counts are best read literally rather than treated as precise safety estimates. The registry lists 12 outcome measures but 0 analyses, emphasizing that registering outcomes is different from reporting statistical results. Without estimates and uncertainty measures, readers cannot judge effect magnitude, precision, or the consistency of findings.
For clinical researchers, the central statistical lesson is that the strength of a conclusion depends on the data available for the question being asked. Here, the primary PK question remains unanswered in the registry record. The same caution applies to efficacy and broader safety interpretation.
14. 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 most consequential trial-specific limitation is that no participants enrolled at the sites conducting intensive PK evaluations. Since the primary endpoint was SPR719 Cmax and its description depended on intensive sampling, the registry reports no primary endpoint result. The planned schedule is described, but there are no concentration summaries or comparisons to interpret.
The registry records enrollment as 2 and status as terminated. It does not report the reason for termination, participant disposition, completion of assigned treatment, or whether the termination affected collection of other outcomes. The record therefore cannot establish how much of the intended study was completed or which secondary measurements were available.
The reported adverse-event summary covers SPR720 500 mg and placebo, with one participant at risk in each group for the listed categories. It does not provide event descriptions for the other adverse events, attribution, severity, or timing. It also does not provide a comparable safety summary for SPR720 1000 mg or SOC in the registry record recorded. These limitations preclude broad safety comparisons.
The record names multiple outcomes but reports no analyses. It does not describe analysis populations, missing-data handling, the statistical analysis plan, multiplicity procedures, or the reason for study termination. The relation between the partially blinded description, quadruple masking, and open-label SOC is not explained. These reporting gaps restrict assessment of both internal validity and generalizability; they should not be filled by assumptions about how the trial was conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease — NCT04553406.
- Registry record last updated 2022-02-28; status last verified 2021-11.
- Results first posted 2022-02-28.
- 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.
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18. Record Summary
NCT04553406 is a randomized, parallel, multicenter phase 2a study of SPR720 for MAC pulmonary disease. The design included SPR720 500 mg, SPR720 1000 mg, placebo, and investigator-discretion SOC. SPR720 and placebo were described as once-daily oral regimens for 28 days. The registry records enrollment of 2 and a terminated status.
The primary endpoint was SPR719 Cmax, with planned sampling on Day 1 and Day 28. No participants enrolled at sites conducting intensive PK evaluation, and no primary endpoint result is reported. The registry lists 12 outcome measures and 0 analyses. Its adverse-event summary lists no serious events in the SPR720 500 mg and placebo groups and reports an other adverse event in each. Comparative efficacy, complete safety findings, analysis methods, and the reason for termination are not reported in the registry record.