ECOSPOR IV: An Open-Label Study Evaluating SER-109 in Recurrent Clostridioides Difficile Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ECOSPOR IV: An Open-Label Study Evaluating SER-109 in Recurrent Clostridioides Difficile Infection (NCT03183141), a na phase 3 study. The primary outcome is Cohort 1: Recurrence of CDI and Sustained Clinical Response.

2. Clinical Question

3. Trial Design

ECOSPOR IV is listed as a Phase 3, open-label study evaluating SER-109 for recurrent Clostridioides difficile infection. Its design is single-group, with allocation listed as NA and masking listed as none. The registry record reports enrollment of 263 and a completed status. The recorded study start was 2017-10-23, and primary completion was 2022-04-29.

The study description distinguishes two cohorts. Cohort 1 concerned participants who had a CDI recurrence in SERES-012 within 8 weeks after receiving study drug. The stated purpose was to assess safety and efficacy of SER-109 in adults with that recurrence history, including people who had received SER-109 or placebo in SERES-012. Cohort 2 was an open-label program for people not part of SERES-012, aged 18 years or older, with at least a first CDI recurrence; its stated purpose was to describe safety and tolerability.

All participants in the current study received an oral dose of SER-109, according to the arm description. Because the current study is single-group and open-label, it does not provide a concurrent randomized comparison. Prior receipt of SER-109 or placebo in SERES-012 is part of the Cohort 1 history, not evidence of a randomized comparison within ECOSPOR IV. The registry record does not report the detailed treatment schedule, dose amount, adherence information, or additional eligibility criteria.

The primary endpoint is described for Cohort 1 and covers recurrence and sustained clinical response up to Week 8. The analysis population is described as all enrolled participants. Whether the primary endpoint count includes Cohort 2 or how Cohort 2 contributes to the primary analysis is not reported in the registry record. No statistical analyses are listed in the record, and it does not provide a numerical result for the primary endpoint.

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: The analysis population consisted of all enrolled participants.

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 Cohort 1: Recurrence of CDI and Sustained Clinical Response, measured over Up to Week 8.

The primary endpoint is titled “Cohort 1: Recurrence of CDI and Sustained Clinical Response.” It is measured as a count of participants, with a timeframe of up to Week 8 after treatment. The description defines recurrence using a stool Clostridioides difficile toxin assay. Sustained clinical response means the absence of CDI recurrence through that same period.

Counting participants with an event is a way to describe how often a defined outcome occurred in the population under analysis. The recurrence definition gives the outcome an operational measurement rule, while the follow-up period specifies when recurrence contributes to the endpoint. Sustained clinical response expresses the complementary clinical status in terms of no recurrence during follow-up. Those definitions help make the endpoint interpretable, but a count alone does not convey uncertainty or support a comparison unless the relevant denominators and analysis are also available.

The registry record says the analysis population consisted of all enrolled participants, although the endpoint title and description specify Cohort 1. This distinction matters when interpreting any count because the population represented by the endpoint must be clear. The record does not explain the relationship between these descriptions. It also does not report the primary endpoint’s observed counts or denominators. Consequently, the endpoint definition can be described, but its numerical result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design tell readers?

In general, a single-group study describes outcomes among people who received the study intervention, rather than estimating a difference against a concurrent randomized group. A count or rate from such a study can be informative as a description of the observed participants, but it does not by itself separate the intervention’s contribution from other influences. These may include participant characteristics, clinical course, and differences in how outcomes are detected. This is a general limitation of the design, not a claim about what influenced outcomes in ECOSPOR IV.

The registry record identifies ECOSPOR IV as single-group, open-label, and with no masking. It lists allocation as NA. It does not report a statistical comparison between SER-109 and a concurrent control group. Although Cohort 1 participants may previously have received SER-109 or placebo in SERES-012, their earlier study assignment is not a randomized control group within this record.

How should a count endpoint be understood?

In general, an event count records the number of participants who meet an outcome definition. To interpret a count as a frequency, the analysis population and denominator also need to be clear. A confidence interval, when reported, describes uncertainty around an estimate under the assumptions of the method used; it does not correct bias caused by study design or incomplete follow-up. No confidence interval or numerical primary endpoint result is reported in the registry record.

Here, the endpoint is defined as recurrence and sustained clinical response up to Week 8. The recurrence criterion is a stool C. difficile toxin assay, and sustained clinical response is absence of recurrence up to Week 8. The analysis population is described as all enrolled participants, but the endpoint is identified with Cohort 1. The record does not clarify the population scope or give the endpoint counts and denominators. These omissions prevent a complete interpretation of the endpoint measure.

What can open-label status affect?

In general, open-label status means participants and study personnel are not masked to treatment assignment. Awareness can affect behavior, care processes, reporting, and assessment, depending on the outcome and study procedures. A laboratory assay may use a defined measurement rule, but open-label status alone does not establish how specimen collection, follow-up, or other decisions were handled. The registry record does not report details sufficient to assess those processes for this study. This is a general methodological consideration, not evidence that any particular bias occurred.

What are the limits of the posted statistical information?

The registry record lists no statistical analyses. It does not report an inferential method for the primary endpoint, a confidence interval, a hypothesis test, an adjustment strategy, or missing-data procedures. Those details are therefore not reported in the registry record. A reader should not infer a statistical plan from the endpoint definition alone.

General planning calculations can illustrate the sample size needed under stated assumptions, but such illustrations are not results from the trial and are not observed power. The planning assumptions associated with this record use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event calculations, the illustration concerns total events using the Schoenfeld method; other illustrations concern participants per arm. These assumptions describe hypothetical planning, not the actual single-group design of ECOSPOR IV. Numerical planning results and the observed effect used for them are not reported in the registry record.

Over-dispersion is a general issue when count outcomes vary more than a model assumes. If present and not accounted for, it can make uncertainty estimates too narrow. The primary endpoint is described as a count of participants, not as a rate model, and the record does not report a count-model analysis or a dispersion estimate. It would therefore be inappropriate to claim that over-dispersion was present or that a particular method addressed it.

For any outcome, clear reporting ordinarily includes the analysis population, outcome definition, denominator, handling of missing observations, and uncertainty estimate. Here, the endpoint’s population wording is not fully aligned across its description, and the numerical results and analysis methods are absent. The registry record also does not report interim analyses, a sample-size justification, or further details of a statistical analysis plan. The presence of a completed status does not fill these reporting gaps.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and zero statistical analyses. It does not report whether the outcomes were assigned a hierarchy, whether multiple hypotheses were tested, or whether any multiplicity adjustment was planned or used. These matters are not reported in the registry record. Without an analysis plan and results, it is not possible to determine how multiple outcomes were handled or whether a particular result was intended as confirmatory.

Missing-data methods are also not reported in the registry record. The entry does not describe how missing endpoint observations, withdrawals, incomplete follow-up, or unavailable toxin assay results were treated. In general, missing observations can affect both the estimated outcome frequency and its uncertainty, and different assumptions about missingness can lead to different interpretations. No such assumptions or sensitivity analyses are described.

The stated analysis population is all enrolled participants, while the primary endpoint is identified as a Cohort 1 outcome. The record does not clarify whether that population statement applies to the endpoint as written, or how Cohort 2 is handled in relation to it. This scope ambiguity should be kept distinct from missing-data questions: the record does not explain either the cohort inclusion for the endpoint or the treatment of incomplete observations.

No primary endpoint results or inferential analyses are listed. Accordingly, multiplicity, missing-data handling, and the analysis population cannot be evaluated from numerical findings. These details are not reported in the registry record.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urosepsis (3.4%), cellulitis (1.7%), clostridium difficile infection (1.7%), urinary tract infection (1.3%), clostridium difficile colitis (0.9%).

The adverse-event entries list affected counts for Cohort 1 and Cohort 2, alongside the corresponding numbers described as at risk. In Cohort 1, the serious-event category lists 1 affected among 29 at risk, and the other-event category lists 14 affected among 29 at risk. In Cohort 2, the serious-event category lists 32 affected among 234 at risk, and the other-event category lists 68 affected among 234 at risk. The death counts listed are 0 for Cohort 1 and 8 for Cohort 2.

The record also lists selected serious-event terms with percentages: Urosepsis, 3.4%; Cellulitis, 1.7%; Clostridium difficile infection, 1.7%; Urinary tract infection, 1.3%; Clostridium difficile colitis, 0.9%; and Corona virus infection, 0.9%. These are descriptive entries; the registry record does not provide enough detail to infer a comparison between cohorts or attribute an event to SER-109.

In general, an affected-participant count is not necessarily the same as a count of all events, since one participant may have multiple events. The record does not explain whether categories overlap, how seriousness was classified, or the exact derivation and denominators for the listed term percentages. These safety figures should therefore be read as descriptive registry entries, not as evidence of comparative risk or causation.

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

The registry record documents a Phase 3, open-label, single-group study of SER-109 in two cohorts with recurrent CDI. It defines a Cohort 1 endpoint involving recurrence and sustained clinical response up to Week 8 and identifies a stool toxin assay as the recurrence measure. It also includes adverse-event counts and selected serious-event terms. These details establish what the study set out to describe and provide some context for reading its safety entries.

The record does not report numerical results for the primary endpoint. It therefore does not establish the observed number of participants with recurrence or sustained clinical response, the denominator for those outcomes, or the precision of an estimate. No statistical analyses are listed. The entry cannot support a quantified efficacy interpretation from the primary endpoint information available in the registry record.

The design also matters to what the study can establish. A single-group, open-label study has no concurrent randomized control comparison described in this record. Descriptive outcomes among enrolled participants cannot, on their own, establish how outcomes would have differed under another treatment. Cohort 1 participants’ prior SERES-012 treatment history does not constitute a current-study randomized comparison. Cohort 2 has a separate stated purpose focused on describing safety and tolerability.

These limitations do not mean that the study has no statistical information. Its design, endpoint definitions, cohort descriptions, enrollment, and some adverse-event entries are reported. They do mean that conclusions must stay within those details. The analysis-population statement and Cohort 1 endpoint description do not fully specify the endpoint’s population scope, and analysis methods and missing-data procedures are not reported in the registry record. The appropriate reading is therefore descriptive and bounded: the record identifies the questions and reporting framework, but it does not provide the primary endpoint results needed to assess the observed outcome or its statistical precision.

13. Why This Trial Matters Statistically

This trial illustrates why study design and outcome reporting need to be read together. ECOSPOR IV is described as open-label and single-group, while its primary endpoint is a count of participants with recurrence and sustained clinical response through Week 8. The endpoint definition identifies how recurrence was determined and the time period used. Yet without the observed counts, denominators, and uncertainty estimates, the outcome cannot be evaluated quantitatively from the registry record.

The two-cohort structure also demonstrates why population definitions matter. Cohort 1 is linked to the primary endpoint and a recurrence history in SERES-012; Cohort 2 is an open-label program for adults not in that earlier study. At the same time, the analysis population is described as all enrolled participants. A clear account of how each cohort contributes to each endpoint is essential for interpreting a count or rate. That relationship is not reported in the registry record.

Finally, the record separates descriptive safety information from an efficacy comparison. Event counts and selected serious-event terms can describe what was recorded, but they do not create a concurrent control group or establish causation. The entry lists no statistical analyses, and it does not provide the primary outcome results. Statistically, the key lesson is that a well-defined outcome and a completed study status are not substitutes for transparent results, population details, and analysis methods.

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.

Several limitations are specific to the information recorded for this study. First, the primary endpoint is described for Cohort 1, while the stated analysis population is all enrolled participants. The registry record does not clarify how these descriptions fit together or whether Cohort 2 contributes to the endpoint analysis. This leaves uncertainty about the population represented by any primary endpoint count.

Second, the record provides no numerical primary endpoint result. It does not state the number of Cohort 1 participants with recurrence or sustained clinical response, the relevant endpoint denominators, or an uncertainty estimate. The listed total enrollment does not resolve the cohort-specific endpoint denominators. No statistical analyses are listed, so the registry record does not explain how any endpoint estimate was calculated.

Third, the design is open-label and single-group, with no concurrent randomized comparator described. The earlier SERES-012 treatment history for Cohort 1 does not supply a randomized comparison within this study. Cohort 2 is described as a separate open-label program, not a control group. Consequently, the design described in the record is limited to reporting outcomes in the study cohorts rather than a controlled treatment contrast.

Fourth, the record does not report a sample-size justification, interim analyses, a detailed statistical plan, missing-data methods, or multiplicity handling. It also does not provide details about the derivation of the listed adverse-event term percentages or the relationship between participants affected and total events. These items are not reported in the registry record and should not be inferred from the available counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: ECOSPOR IV: An Open-Label Study Evaluating SER-109 in Recurrent Clostridioides Difficile Infection — NCT03183141.
• Registry record last updated 2023-04-10; status last verified 2023-04.
• Results first posted 2023-03-31.
• 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.

18. Record Summary

NCT03183141 is a completed Phase 3, open-label, single-group study evaluating oral SER-109 for recurrent Clostridioides difficile infection. The registry record reports enrollment of 263, a start date of 2017-10-23, and primary completion on 2022-04-29.

The study describes Cohort 1, whose participants had a CDI recurrence in SERES-012 within 8 weeks after study drug, and Cohort 2, an open-label program for adults outside SERES-012 with at least a first recurrence. The primary endpoint is recurrence and sustained clinical response up to Week 8 in Cohort 1, measured using a stool toxin assay for recurrence. Numerical primary endpoint results and statistical analyses are not reported in the registry record. Selected adverse-event counts and serious-event terms are listed, but the record does not establish a randomized comparison.