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 A Study of RSLV-132 in Subjects With Primary Sjogren's Syndrome (NCT03247686), a randomized phase 2 study. The primary outcome is Blood Cell Gene Expression.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03247686 |
| Phase | Phase 2 |
| Condition | Sjogren's Syndrome |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 28 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Resolve Therapeutics |
| Results posted | Yes |
2. Clinical Question
The study asked whether RSLV-132 was associated with a change in interferon-inducible gene expression in blood cells among selected people with primary Sjögren's syndrome. The registry describes a population with elevated autoantibodies and an elevated interferon-stimulated gene expression pattern. Its stated rationale concerns circulating RNA complexed with autoantibodies and immune complexes, and the role of these complexes in inflammatory pathway activation.
Population
People with primary Sjögren's syndrome selected for elevated autoantibodies and an elevated interferon-stimulated gene expression pattern in blood cells. The registry record lists an enrollment of 28.
Intervention
RSLV-132, described in the record as an experimental drug. The registry does not report dosing details in the information available for this analysis.
Comparator
Placebo. The study is described as placebo-controlled and randomized.
Primary question
What was the mean change from baseline to Day 99 in blood-cell expression of the interferon-inducible genes HERC5, EPSTI1, and CMPK2, measured as log 2 fold change?
This is a biomarker question rather than a direct question about how participants felt or functioned. The registry also names EULAR ESSDAI Total Score as a secondary outcome, but it does not report that outcome's results in the record details available for this analysis. The primary endpoint's numerical estimates and treatment comparison are likewise not reported in the registry record, so the clinical question can be described but not answered from the posted results.
3. Trial Design
This was a phase 2, randomized, quadruple-masked, parallel-group, placebo-controlled study of RSLV-132 in primary Sjögren's syndrome. The listed enrollment is 28, and the study status is completed. The record gives a start date of 2017-02-01 and a primary completion date of 2018-07-15. It names Resolve Therapeutics as the sponsor.
Random allocation is intended to make treatment groups comparable on average at the start of a study, while a parallel design means participants are assigned to a group and followed in that group rather than switching between treatments. Placebo control gives the trial a comparison group for assessing the outcome under the study conditions. The record labels masking as quadruple, but does not report which roles or individuals were masked, how masking was maintained, or whether it was assessed.
The registry describes the enrolled population as a subset of people with Sjögren's syndrome who had elevated autoantibodies and an elevated interferon-stimulated gene expression pattern in blood cells. This selection is relevant to interpretation: the study's biomarker question concerns a specified biological profile, and the findings, if reported, would pertain directly to that study population. The record does not report detailed eligibility criteria or the allocation ratio.
Safety-group counts list 8 participants at risk in the placebo group and 20 in the RSLV-132 group. These are the counts associated with the safety outcomes; the registry information does not establish that they are the analysis populations for the primary endpoint. The primary endpoint is described as blood-cell gene expression measured at Day 1 and Day 99. Details of visit windows, treatment duration, dosing, adherence, and follow-up beyond the named timeframe are not reported in the registry record.
The record does not report the planned sample-size justification, the randomization method, or the intended statistical analysis plan. Those details should not be inferred from the study's phase or design labels.
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.
Before assignment: Participants were randomized in a 3:1 ratio to either RSLV-132 or placebo. A total of 22 participants were randomised to RSLV-2 and 8 to placebo. Two participants randomized to RSLV-2 were withdrawn prior to the start of study treatment, one withdrew consent and one was found not to meet the eligibility criteria.
Overall Study
| Stage | Placebo | RSLV-132 |
|---|---|---|
| STARTED | 8 | 20 |
| COMPLETED | 7 | 18 |
| NOT COMPLETED | 1 | 2 |
Reasons for not completing this period:
| Reason | Placebo | RSLV-132 |
|---|---|---|
| Withdrawal by Subject | 1 | 2 |
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: All participants randomized who received at least one dose of study treatment (RSLV-132 or placebo).
| Characteristic | Unit | Placebo | RSLV-132 | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 20 | 28 | |
| Age, Continuous | years | 59.6 (SD 8.8) | 56.5 (SD 12.9) | 57.4 (SD 11.8) |
| Sex: Female, Male: Female | Participants | 8 | 20 | 28 |
| 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 | 8 | 19 | 27 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 7 | 19 | 26 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United Kingdom | participants | 8 | 20 | 28 |
| EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) Total Score | Scores on a scale | 5.1 (SD 4.1) | 5.0 (SD 4.6) | 5.1 (SD 4.4) |
6. Primary Endpoint
The registry lists the primary outcome as Blood Cell Gene Expression, measured over Day 1 and Day 99.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | log 2 fold change |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is titled Blood Cell Gene Expression. It measures interferon gene expression as mean log 2 fold change from baseline to Day 99. The registry says that expression of HERC5, EPSTI1, and CMPK2, described as interferon-inducible genes, was measured by quantitative polymerase chain reaction to assess the interferon signature in people with Sjögren's syndrome. The listed timeframe is Day 1 and Day 99.
In general, a biomarker endpoint records a biological measurement rather than a direct measure of symptoms, daily functioning, or a clinical event. A gene-expression measure can be used to assess whether a biological signal changes during a study. The record's rationale is to examine the role of circulating RNA and immune complexes in inflammatory pathway activation and the potential therapeutic utility of nuclease therapy. This rationale explains why the endpoint was of interest; it does not establish that a change in the marker would correspond to a change in how participants feel or function.
The registry identifies the endpoint summary as a mean and its dispersion as a standard error. A mean describes the average measured change in a group. A standard error describes the precision of an estimated mean, not the spread of individual participants' measurements. However, the numerical endpoint estimates, their standard errors, and the between-group comparison are not reported in the registry record. Without those values, the direction, size, and precision of the observed primary outcome cannot be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies a randomized comparison of RSLV-132 with placebo and describes a primary biomarker endpoint, but it does not report the primary endpoint's numerical results. There is therefore no posted mean change, treatment contrast, confidence interval, or p-value to interpret. The registry record does not establish whether the measured gene expression was higher or lower in either group, how large any difference was, or how uncertain an estimate might be.
The outcome is mean log 2 fold change from baseline to Day 99 in expression of HERC5, EPSTI1, and CMPK2. A treatment comparison would need to be interpreted in relation to that defined scale and timeframe. A group mean alone would not show how much individual measurements varied; a standard error or confidence interval would help describe uncertainty around an estimate. Neither the endpoint estimates nor their uncertainty measures are reported in the registry record.
General statistical interpretation distinguishes an estimated effect from the evidence about its precision. A confidence interval gives a range of values compatible with the data under the analysis assumptions. A p-value, when reported, addresses how compatible the data are with a specified null hypothesis under those assumptions; it does not measure the probability that a treatment works. Since neither is reported for the primary comparison, no conclusion about statistical compatibility or precision can be drawn from the posted results.
The study's biomarker focus also limits what the endpoint could answer even if its numerical results were available. A change in gene expression is not itself a direct measurement of symptoms, function, disease complications, or quality of life. The registry names EULAR ESSDAI Total Score as a secondary outcome, but does not report its result in the available record. The primary biomarker and the secondary clinical measure therefore cannot be compared or connected using the information reported.
The enrollment and safety-group counts provide context for the study's scale, but they do not supply the missing primary outcome comparison. No new estimate should be reconstructed from counts alone. The record also does not report the analysis population, missing endpoint data, or adjustments used in an analysis. Those omissions prevent assessment of how the primary comparison was formed and whether the reported analysis, if any, included all randomized participants.
In short, the record documents the design and intended biomarker question, and it contains selected safety counts. It does not provide the efficacy results needed to characterize the observed treatment contrast. The appropriate reading is that the primary result is not reported in the registry record, rather than that the study found no effect or found a particular effect.
9. Statistical Methods Explained
The central statistical task in this trial would be to compare a continuous gene-expression outcome between randomized groups over the stated baseline-to-Day 99 timeframe. The registry describes the outcome as a mean and identifies standard error as the dispersion measure. It does not report the group estimates, the treatment contrast, or the procedure used to estimate that contrast. The explanations below are general descriptions of the statistical ideas relevant to this kind of outcome; they are not claims about analyses performed in this trial.
What does a mean describe?
For a continuous measure, a mean is an average across the observations included in an analysis. Here, the defined measure is log 2 fold change in expression of HERC5, EPSTI1, and CMPK2 from baseline to Day 99. A group mean would describe the average change for that group under the study's measurement and analysis procedures. It would not imply that every participant changed by that amount, nor would it describe the full distribution of participant-level results.
Comparisons are often expressed as a difference between group means or as an adjusted estimate from a statistical model. The choice depends on the prespecified analysis and available data. The registry record does not report the exact comparison estimand, any adjustment variables, or whether the mean was analyzed using a model. Consequently, an unadjusted comparison or a model-based comparison should not be attributed to this study.
What does standard error tell a reader?
In general, a standard error describes the uncertainty in an estimated statistic, such as a group mean. It is not the same as the standard deviation, which describes variation among individual observations. Standard errors can help readers judge how precisely an average has been estimated, but they do not show the range of individual responses. The record specifies standard error as the endpoint's dispersion measure, but the numerical standard errors are not reported in the registry record.
A confidence interval is a commonly used way to express estimate uncertainty. It gives a range of values compatible with the observed data under the statistical method and its assumptions. The width of the interval conveys precision: a narrower interval indicates greater precision than a wider one on the same scale. No confidence interval for the primary endpoint is reported in the available record, so its precision cannot be evaluated.
How should a p-value be understood?
In general, a p-value is calculated relative to a specified null hypothesis and statistical model. It describes how unusual the observed data, or data more extreme, would be if that null model were correct. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A p-value should be considered alongside an effect estimate and its uncertainty. The primary comparison's p-value and the hypothesis tested are not reported in the registry record.
Why does the outcome scale matter?
The named outcome is on a log 2 fold-change scale. In general, transformed scales express measurements differently from their original scale, so interpretation should stay tied to the definition and units used by the study. The registry describes the measure as mean log 2 fold change from baseline to Day 99. It does not give the underlying gene-expression values, a transformation procedure beyond the stated scale, or details on how the measurements from the three genes were combined into an endpoint. Those aspects are not reported in the registry record and should not be assumed.
What role does randomization play?
In general, random allocation helps balance known and unknown characteristics across groups in expectation. It does not guarantee that every characteristic will be balanced in a particular trial, especially when the study is small. A valid treatment comparison also depends on how participants were analyzed, how missing measurements were handled, and whether the analysis followed the planned method. The registry labels the study randomized, but the method of sequence generation, allocation concealment, and primary analysis are not reported in the registry record.
These concepts explain what would be needed to interpret a continuous endpoint rigorously. They cannot replace the trial's numerical estimates or an account of its analysis. Since those results and methods are not reported, the treatment contrast and its statistical precision remain unknown from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures and 10 analyses, but does not describe the individual analyses, their hypotheses, or how they relate to the primary and secondary outcomes. It does not report whether the trial used a multiplicity procedure, such as adjusting inference when several comparisons are made, or whether a particular comparison was designated as the main confirmatory test. The outcome and analysis counts alone do not establish how multiplicity was handled.
Multiplicity matters in general when several outcomes, time points, genes, subgroups, or statistical comparisons are examined. As the number of opportunities to identify a striking result grows, the interpretation of individual p-values can change unless the analysis plan accounts for that structure. This is a general consideration, not a statement that a particular adjustment was necessary or performed in this study. The registry's primary endpoint describes three genes and a baseline-to-Day 99 measure, but the method used to combine or analyze those measurements is not reported in the registry record.
The record does not report the amount of missing primary endpoint data, reasons for missingness, or the method used to handle missing measurements. It also does not describe whether any sensitivity analyses were performed. Missing data can affect an estimate when the observed participants differ systematically from those whose measurements are missing; the direction and extent of any effect depend on the data and assumptions. No such assessment can be made from the information reported.
The primary analysis population is not reported in the registry record. It is therefore unclear whether the primary outcome analysis included all randomized participants, participants who received treatment, or a defined subset with available measurements. The safety counts should not be treated as the primary endpoint analysis population without evidence that they are the same. The registry also does not report interim analyses or a stopping rule. None should be inferred from the trial design or completion status.
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 |
|---|---|---|---|
| Placebo | 0 | 8 | 0.0% |
| RSLV-132 | 1 | 20 | 5.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 0 of 8 |
| RSLV-132 | 0 of 20 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 8 of 8 |
| RSLV-132 | 20 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | RSLV-132 |
|---|---|---|---|
| Parotitis | Infections and infestations | 0 of 8 | 1 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | RSLV-132 |
|---|---|---|---|
| Fatigue | General disorders | 1 of 8 | 6 of 20 |
| Upper respiratory tract infection | Infections and infestations | 2 of 8 | 5 of 20 |
| Viral upper respiratory tract infection | Infections and infestations | 1 of 8 | 4 of 20 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 0 of 8 | 5 of 20 |
| Conjunctivitis | Infections and infestations | 1 of 8 | 3 of 20 |
| Lower respiratory tract infection | Infections and infestations | 3 of 8 | 1 of 20 |
| Headache | Nervous system disorders | 1 of 8 | 3 of 20 |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 1 of 8 | 2 of 20 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 8 | 2 of 20 |
| Palpitations | Cardiac disorders | 1 of 8 | 1 of 20 |
Serious events with the highest arm-level rate: parotitis (5.0%).
The safety record lists 8 participants at risk in the placebo group and 20 in the RSLV-132 group. It records 0 serious adverse events in the placebo group and 1 in the RSLV-132 group. Deaths are listed as 0 in both groups. The top serious adverse event term is Parotitis, listed as 5.0%.
These counts are descriptive. They do not, by themselves, establish that the groups had different underlying risks, and the record does not provide an inferential comparison for serious adverse events. The counts also do not describe severity beyond the serious-event classification, timing, duration, relatedness to treatment, or the clinical course. Those details are not reported in the registry record.
The record also lists other adverse events affecting 8 of 8 participants at risk in the placebo group and 20 of 20 in the RSLV-132 group. These figures should be read as registry-reported counts, not as a comparison of event severity or treatment causation. The listed Parotitis percentage does not identify an arm in the available information, so it should not be assigned to a particular group. With the limited counts reported, safety findings are best described as observed registry entries, not as proof of a causal treatment effect or a complete account of harms.
12. What the Result Does, and Does Not, Mean
This trial's record establishes that a randomized, placebo-controlled phase 2 study of RSLV-132 was conducted in a selected primary Sjögren's syndrome population. It specifies a primary biological measure: mean log 2 fold change from baseline to Day 99 in expression of interferon-inducible genes in blood cells. It also reports selected serious adverse event and death counts. These details describe the question, design, and some safety observations.
The record does not report the numerical primary endpoint results. It therefore cannot show whether mean gene expression changed in either group, whether the groups differed, how large any contrast was, or how precisely it was estimated. This absence is not evidence of no effect, and it is not evidence of a beneficial or harmful effect. It means the primary treatment comparison cannot be evaluated from the information reported in the registry record.
Even a reported change in this biomarker would not, by itself, establish a change in symptoms or other clinical outcomes. Biomarkers can inform biological questions, but their clinical meaning depends on the relationship between the marker and outcomes that matter to participants. The registry names EULAR ESSDAI Total Score as a secondary outcome, but its results are not reported in the record details available for this analysis. No connection between the gene-expression endpoint and clinical status can therefore be assessed.
The safety counts are also limited. They record one serious adverse event in the RSLV-132 group and none in the placebo group, with no deaths listed in either group. These observations are not a causal comparison and do not describe all dimensions of safety. The registry does not report event timing, relatedness, or detailed clinical follow-up.
Accordingly, the record supports a description of the study's design and intended measurement, but not a conclusion about the primary result or the treatment's clinical effects. A fuller interpretation would require the outcome estimates, uncertainty, analysis population, missing-data information, and a clear account of the planned and performed analyses.
13. Why This Trial Matters Statistically
This study is statistically notable for focusing on a biomarker in a selected population rather than relying only on a broad clinical outcome. The registry describes participants with elevated autoantibodies and an elevated interferon-stimulated gene expression pattern. That selection connects the eligibility concept to the biological question: whether the expression of specified interferon-inducible genes changes over the study timeframe.
The design includes randomization and a placebo comparator, features intended to support a fair comparison between groups. The parallel structure also gives a straightforward framework for comparing outcomes measured over time. However, the usefulness of that framework depends on reporting the treatment contrast, its uncertainty, and the analysis procedures. Those primary outcome results and methods are not reported in the registry record.
The endpoint illustrates why statistical interpretation requires more than an outcome name. Readers need to know how a gene-expression measure was constructed, which observations were included, what comparison was estimated, and how uncertain that estimate is. The record identifies the genes, measurement approach, unit, and timeframe, but does not report the numerical results or details of the analysis. Thus the biological focus is clear while the statistical result remains unavailable.
The record also distinguishes a biomarker question from a clinical-outcome question. EULAR ESSDAI Total Score is listed as a secondary outcome, but no result is reported for it. This makes the difference between biological activity and clinical status especially important: evidence about one measure cannot automatically be substituted for evidence about the other.
Finally, the study emphasizes the value of complete registry reporting. Design labels and safety counts can orient readers, but estimates, uncertainty, analysis populations, and missing-data handling are necessary to evaluate a treatment comparison. Without those elements, the trial can be described statistically, but its primary result cannot be independently interpreted from the registry record.
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 main limitation for interpreting this trial is that the primary endpoint's numerical results are not reported in the registry record. No group means, treatment contrast, standard errors, confidence intervals, or p-values are available in the record details used for this analysis. As a result, neither the direction nor the magnitude nor the precision of the primary comparison can be assessed.
The endpoint description does not explain how expression measurements from HERC5, EPSTI1, and CMPK2 were combined or whether gene-specific results were analyzed separately. The record identifies quantitative polymerase chain reaction and the log 2 fold-change scale, but does not report details of normalization, quality control, or the statistical model. The exact estimand and any covariate adjustment are also not reported in the registry record.
The primary endpoint analysis population and missing-data methods are not reported. Without those details, it is not possible to determine which participants contributed to the analysis or how absent measurements were handled. The safety-group counts do not establish the population used for the efficacy analysis.
The registry describes a selected population with elevated autoantibodies and an elevated interferon-stimulated gene expression pattern. This narrows the population to which any result would directly apply. Further eligibility details and participant characteristics are not reported in the record details used. The registry also does not report the randomization procedure, allocation concealment, dosing details, adherence, or masking roles.
Finally, the record lists EULAR ESSDAI Total Score as a secondary outcome but does not report its results. It does not describe multiplicity handling, interim analyses, or a sample-size justification. These omissions limit assessment of how the study was planned and analyzed; they should not be filled in by assumption.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of RSLV-132 in Subjects With Primary Sjogren's Syndrome — NCT03247686.
- Registry record last updated 2021-04-02; status last verified 2020-10.
- Results first posted 2021-04-02.
- 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
The registry describes a completed, randomized, quadruple-masked, parallel-group, placebo-controlled phase 2 study of RSLV-132 in primary Sjögren's syndrome. Listed enrollment is 28. The primary endpoint is mean log 2 fold change from baseline to Day 99 in blood-cell expression of HERC5, EPSTI1, and CMPK2, measured by quantitative polymerase chain reaction. EULAR ESSDAI Total Score is listed as a secondary outcome.
Safety counts list 1 serious adverse event in the RSLV-132 group and 0 in the placebo group, with 0 deaths in both groups. The registry record does not report the primary endpoint estimates, the treatment comparison, or the statistical methods needed to assess its precision. It also does not report the secondary outcome results, analysis populations, or missing-data handling. The record therefore defines the study question and design, but does not supply the results needed to evaluate the primary comparison.