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 3-year, Open-Label Study Evaluating Safety, Tolerability, and Efficacy of Lorecivivint in Knee Osteoarthritis (NCT04931667), a na phase 3 study. The primary outcome is Change From Baseline in Pain Numeric Rating Scale (NRS) Score for the Left Knee.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04931667 |
| Phase | Phase 3 |
| Condition | Osteoarthritis of the Knee |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 72 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Biosplice Therapeutics, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People with osteoarthritis of the knee were enrolled. The registry record lists 72 participants. Further eligibility details and a more complete description of the analyzed population are not reported in the registry record.
Intervention
The study evaluated a healthcare professional-administered intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle. Injection in one or both knees was permitted, as clinically indicated; bilateral injections were allowed.
Comparator
There was no control group or randomized comparison. The design is listed as single-group, with allocation recorded as NA and masking recorded as NONE. Comparisons with another treatment or with placebo therefore cannot be made from this study design.
Primary question
The planned primary endpoint was change from baseline in the left-knee pain Numeric Rating Scale score at three months after the Day 1 injection. The registry record states that efficacy analyses were not performed because the study ended early for administrative reasons. Efficacy was therefore not formally assessed.
The study was intended to evaluate safety, tolerability, and efficacy in a real-world setting. Its open-label, single-group structure describes experience among participants receiving lorecivivint, but it does not isolate an effect attributable to the injection from other influences on reported pain or clinical care. The registry record does not contain a formal efficacy analysis for the primary question.
3. Trial Design
This was a Phase 3, multicenter, open-label study of intra-articular lorecivivint in people with osteoarthritis of the knee. It was planned as a 3-year study in a real-world setting. The study began on 2021-07-15, had a primary completion date of 2021-12-13, and is recorded as TERMINATED. The registry describes the termination as being for administrative reasons.
The design is listed as SINGLE GROUP, allocation as NA, and masking as NONE. Participants received 0.07 mg lorecivivint in 2 ml vehicle by injection into one or both knees, as clinically indicated. Bilateral injection was allowed. There was no randomized or concurrent control arm, so the study cannot directly compare lorecivivint with placebo or another treatment. Open-label status also means participants and those involved in care were not masked to treatment.
The registry lists enrollment of 72. It does not report whether all enrolled participants received an injection, how many completed the planned follow-up, or the number contributing data to each outcome. The primary endpoint was planned for three months after the Day 1 injection, while the study’s stated duration was 3 years. The registry does not report the reasons for choosing the planned duration or how termination affected each outcome’s collection schedule.
WOMAC physical function and pain changes for the left and right knees are listed as secondary outcomes. There are 6 outcome measures in the record and 0 analyses listed. No efficacy analyses were performed because of early termination and concerns about data completeness. The registry record does not report a detailed protocol-level statistical analysis plan or a sample-size justification.
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 | 0.07 mg Lorecivivint |
|---|---|
| STARTED | 72 |
| COMPLETED | 0 |
| NOT COMPLETED | 72 |
Reasons for not completing this period:
| Reason | 0.07 mg Lorecivivint |
|---|---|
| Lost to Follow-up | 2 |
| Study Terminated by Sponsor | 63 |
| Withdrawal by Subject | 7 |
Analysis population for the primary outcome, as defined in the registry: Efficacy analyses were not performed due to the early termination of the study (administrative reasons). Given the impact of early termination on data completeness, efficacy of LOR for the treatment of knee OA was not formally assessed. Data collected on those subjects completing Month 3 visit are summarized without any imputation for missing data.
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 subjects who received a study injection without previous exposure to Lorecivivint.
| Characteristic | Unit | 0.07 mg Lorecivivint |
|---|---|---|
| Participants analysed | 72 | |
| Age, Continuous | years | 61.5 (SD 9.0) |
| Sex: Female, Male: Female | Participants | 42 |
| Sex: Female, Male: Male | Participants | 30 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 12 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 60 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 |
| Race (NIH/OMB): Black or African American | Participants | 11 |
| Race (NIH/OMB): White | Participants | 58 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Symptomatic OA Laterality by Investigator Assessment: Bilateral | Participants | 58 |
| Symptomatic OA Laterality by Investigator Assessment: Unilateral, Right | Participants | 10 |
| Symptomatic OA Laterality by Investigator Assessment: Unilateral, Left | Participants | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Pain Numeric Rating Scale (NRS) Score for the Left Knee, measured over Three Months after Day 1 Injection.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | units on a scale |
| Endpoint classification | not reduced to a single comparison |
The planned primary endpoint was change from baseline in the pain Numeric Rating Scale score for the left knee, assessed three months after the Day 1 injection. The pain NRS is an 11-point self-report scale ranging from 0 to 10. Participants report their average knee pain over the last 24 hours; 0 indicates no pain and 10 indicates the worst possible pain.
Change was defined as the three-month visit score minus the baseline score. Under this definition, a negative value indicates improvement and a positive value indicates worsening. The endpoint focuses on the participant’s own report of pain in a specified knee and over a specified recent period. A baseline-to-follow-up change can describe whether reported scores shifted during follow-up among participants with data, but without a control group it cannot by itself distinguish an intervention effect from changes due to other factors.
Pain is a patient-reported experience, so a self-report scale offers a direct way to record that experience in a standardized form. The registry does not report the primary endpoint’s observed mean change, variability, confidence interval, or significance test. It states that efficacy analyses were not performed because the study ended early for administrative reasons and data completeness was affected. Thus, the planned endpoint is described, but no formal efficacy result is available in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The key interpretive fact is that the registry does not report a formal efficacy analysis. The primary outcome was specified as left-knee pain NRS change from baseline at three months, but efficacy analyses were not performed following early termination for administrative reasons. The record says that the effect of early termination on data completeness meant efficacy was not formally assessed. Consequently, there is no reported primary-endpoint estimate, uncertainty interval, or hypothesis-test result from which to judge the magnitude or precision of a change.
The planned outcome has a clear direction: a negative change would indicate improvement in the pain score, while a positive change would indicate worsening. That direction rule explains how a reported estimate would be read; it does not imply that either kind of change was observed. No numerical primary outcome result is reported in the registry record, so the direction, size, and consistency of any change cannot be established from it.
The design also limits causal interpretation. Participants received lorecivivint in a single-group, open-label study, without a randomized comparator. In general, a change over time in such a design can reflect the intervention, natural fluctuation in symptoms, expectations, concurrent care, or other influences. Since there is no control group to help distinguish these explanations, and no efficacy analysis was performed, the record does not support an estimate of treatment effect relative to an alternative.
The study enrolled 72 participants, but enrollment is not the same as the number with complete outcome data. The record does not state the number who completed the Month 3 visit or contributed data to the primary endpoint. It also does not report outcome-specific missingness or a statistical method for handling incomplete observations. That makes it impossible to assess how representative any collected Month 3 data might have been, even though the record notes that some participants completed that visit.
The registry lists 6 outcome measures and 0 analyses. WOMAC function and pain changes by knee are among the listed secondary outcomes, but no formal results for them are reported in this record. Overall, the available information characterizes the planned question, study structure, and certain safety counts; it does not quantify efficacy or establish how precisely a treatment effect was estimated.
9. Statistical Methods Explained
The registry describes a planned mean change endpoint, but also states that efficacy analyses were not performed. Statistical concepts can clarify what the planned analysis would represent, while keeping separate the planned endpoint from results that are actually reported.
What does change from baseline represent?
Change from baseline is a follow-up score compared with the participant’s own starting score. For the primary endpoint, the record defines the calculation as the three-month score minus baseline. This makes the sign interpretable: negative values indicate improvement in the pain score, and positive values indicate worsening. A mean change would summarize the average of individual changes among the observations included in an analysis. It would not describe every participant’s experience, and it would not by itself show that the intervention caused the change.
In general, a mean is a measure of the center of a set of values. Its usefulness depends on the distribution of those values and on which participants contributed observations. The registry specifies MEAN and Full Range for the primary outcome but does not report an estimate, the range, or the number of observations used. No result can therefore be interpreted for size or spread from the record.
What would uncertainty quantify?
In general, a confidence interval describes a range of values compatible with the data and the statistical assumptions used to calculate it. It expresses uncertainty in an estimate; it is not a range expected to contain every participant’s individual outcome. The registry does not report a confidence interval for the primary endpoint. Because no efficacy analysis was performed, the precision of a primary-endpoint estimate cannot be assessed.
A significance test, in general, evaluates how compatible data are with a specified null hypothesis under stated assumptions. A p-value is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry record does not report a primary-endpoint test or p-value. No inference about statistical significance should be drawn from the absence of a reported test.
Why does the single-group design matter?
In general, a control group supplies a reference for separating changes associated with the intervention from changes that might also occur without it. Here, the design is single-group, open-label, and has no randomized comparison. A baseline-to-follow-up change, even if it had been analyzed, would therefore be a description of change among participants and not a controlled estimate of the effect of lorecivivint. Open-label treatment can also influence participant expectations and reporting, which matters for a self-reported pain outcome.
General statistical interpretation also depends on the target population and the observations included. Enrollment of 72 does not establish how many participants had a Month 3 score. The record does not report the endpoint analysis population, the number with complete observations, or the treatment of missing data. Without those details, the scope of any potential estimate cannot be determined.
How should planning illustrations be understood?
The registry’s sample-size description characterizes calculations as planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also says the calculations vary the effect to detect as a stated fraction of the observed effect. Such illustrations are not the trial’s own sample-size justification and are not observed power. The trial itself is single-group, so the equal-allocation, two-arm planning assumptions do not describe its actual design. The registry record does not report the protocol’s sample-size rationale.
In general, a sample-size calculation describes the number of observations a hypothetical design would require under its assumptions. It does not show that a study had that probability of detecting an effect after the fact. It also cannot substitute for an analyzed outcome. In this case, no efficacy estimate is reported in the registry, and the statistical assumptions behind any separate illustration should not be confused with observed evidence from the trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 6 outcome measures. The primary endpoint is change from baseline in left-knee pain NRS at three months after the Day 1 injection. The listed secondary outcomes include WOMAC physical function and pain changes for both the left and right knees. The record lists 0 analyses and states that efficacy analyses were not performed. It therefore reports no inferential results across which multiplicity can be evaluated.
In general, multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. The more opportunities there are to identify a result, the more important it is to know which analyses were planned and whether any adjustment or hierarchy was specified. The registry record does not report a multiplicity strategy, a testing hierarchy, or details of which outcomes would have been formally tested. It would be inappropriate to assume that an adjustment was or was not planned.
The registry attributes the absence of efficacy analysis to early termination for administrative reasons and says data completeness was affected. It does not report how much data were missing for each outcome, why particular observations were unavailable, or whether missingness differed among participants. It also does not state an imputation procedure or another method for handling missing outcome values. These details are not reported in the registry record.
The primary outcome description refers to data from subjects completing the Month 3 visit, but the record does not give the number who completed that visit or the number with an evaluable left-knee score. The analysis population and any criteria for inclusion are not reported in the registry record. Enrollment of 72 should therefore not be read as a complete primary-endpoint dataset. Without outcome-specific counts and a stated missing-data approach, the potential influence of incomplete follow-up cannot be quantified.
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 |
|---|---|---|---|
| 0.07 mg Lorecivivint | 0 | 72 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 0.07 mg Lorecivivint | 0 of 72 |
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 |
|---|---|
| 0.07 mg Lorecivivint | 2 of 72 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 0.07 mg Lorecivivint |
|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | 1 of 72 |
| Bacterial Vaginosis | Infections and infestations | 1 of 72 |
The registry lists 72 participants at risk for serious adverse events and 0 participants affected. It also lists 72 participants at risk for other adverse events and 2 affected. Deaths are recorded as 0. These counts describe the adverse-event entries in the registry; they do not provide a comparison with an untreated group or another treatment.
In general, an at-risk count is the group size used for the adverse-event summary, while the affected count indicates how many participants were recorded with an event in that category. These counts do not describe the event’s cause, severity beyond the category shown, duration, or relationship to treatment unless those details are separately reported. The record lists no top serious adverse-event terms, so specific serious-event types are not available in this summary.
Zero serious adverse events recorded in this group should be read as a count in the registry, not as proof that serious events are impossible or that risk is absent. The study was terminated early, and follow-up completeness is a stated concern for efficacy; the record does not give additional details about safety follow-up duration or completeness. The figures are descriptive safety information from a single-group study, not a comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase 3, open-label, single-group study of lorecivivint was planned in knee osteoarthritis and that it was terminated for administrative reasons. It also documents the intended primary endpoint: left-knee pain NRS change from baseline at three months after the Day 1 injection. The record explicitly says that efficacy was not formally assessed because early termination affected data completeness.
What the record does not establish is a numerical estimate of change in pain, its precision, or whether any observed change would differ from what might have occurred without the intervention. No primary-endpoint estimate, confidence interval, or test result is reported. The absence of an efficacy analysis is not evidence that the treatment had no effect; it means that the registry record does not provide a formal efficacy result to evaluate.
The study’s single-group design is important to that interpretation. In general, participants’ symptoms can change over time for reasons other than the intervention. Without a randomized comparator, a before-and-after change cannot separate the intervention’s contribution from those other influences. The open-label design also means that treatment was not masked, which is particularly relevant when the outcome is based on participants’ self-reported pain.
The safety record reports 0 serious adverse events among 72 participants at risk, 2 participants with other adverse events among 72 at risk, and 0 deaths. These are descriptive counts; they do not provide a comparative estimate or a complete account of event details. Together, the efficacy and safety entries should be understood as registry information with important limits, not as a definitive characterization of benefit or risk.
The secondary WOMAC outcomes are listed, but their efficacy results are not reported. The record also does not give the number of participants with complete Month 3 outcome data or a detailed missing-data method. Those omissions further limit what can be concluded about the collected outcomes.
13. Why This Trial Matters Statistically
This study illustrates why planned endpoints and analyzed results need to be distinguished. A registry can specify a clinically relevant measurement and its timing, yet still contain no formal efficacy result when a study ends before the planned assessment can be completed or analyzed. Here, the record identifies left-knee pain NRS change at three months as the primary endpoint, while also stating that efficacy analyses were not performed because of early termination and data-completeness concerns.
The case also shows the interpretive limits of an uncontrolled design. A single-group, open-label study can document treatment exposure, outcome collection plans, and adverse-event counts. In general, however, observed change over time is not equivalent to a controlled treatment effect. A randomized comparator helps distinguish changes associated with treatment from changes that could arise through other influences; no such comparison is present in this design.
Missing-data reporting is another statistical consideration. The study enrolled 72 participants, but the registry does not state how many completed the Month 3 visit or contributed to the primary endpoint. Without outcome-specific counts, readers cannot assess how much information underlies a potential estimate or how incomplete follow-up might affect interpretation. This matters especially when the record itself notes that early termination affected data completeness.
Finally, the record separates planning language from trial evidence. Its sample-size description refers to planning illustrations under two-arm assumptions, whereas the actual study is single-group. Such calculations are not observed power and do not replace an efficacy analysis. Reading these elements together reinforces a general principle: design, data completeness, analysis, and interpretation must align before a clinical effect can be estimated with useful precision.
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 this trial record. The study was planned as a 3-year evaluation but is recorded as terminated, with a primary completion date of 2021-12-13. The stated reason for termination was administrative. The record does not report the timing or operational details of the decision, or how follow-up ended for individual participants.
The registry explicitly states that efficacy was not formally assessed because of early termination and data-completeness concerns. No numerical result for the primary endpoint is reported. Although the primary assessment was planned for three months after the Day 1 injection, the number of participants who completed that visit and the number with evaluable left-knee scores are not reported in the registry record.
The single-group and open-label design prevents a direct randomized comparison. The intervention could be given in one or both knees as clinically indicated, and the record does not report how many participants received unilateral versus bilateral injections. No control group is listed. Thus, the design cannot distinguish an intervention-associated change from other changes over time.
The statistical details needed to assess efficacy are also absent: a primary-endpoint estimate, its variability and uncertainty, the analysis population, a missing-data method, and a multiplicity strategy are not reported in the registry record. The record lists secondary WOMAC outcomes but no analyses. Safety details are limited to event counts; specific serious-event terms are not listed, and further information on event timing or follow-up is not included in the summary.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: 3-year, Open-Label Study Evaluating Safety, Tolerability, and Efficacy of Lorecivivint in Knee Osteoarthritis — NCT04931667.
- Registry record last updated 2026-03-31; status last verified 2026-03.
- Results first posted 2026-03-31.
- 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.
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18. Record Summary
NCT04931667 is a Phase 3, multicenter, open-label, single-group study of intra-articular lorecivivint for osteoarthritis of the knee. The planned regimen was 0.07 mg in 2 ml vehicle, injected into one or both knees as clinically indicated. The registry lists enrollment of 72 and records the study as terminated for administrative reasons.
The primary endpoint was left-knee pain NRS change from baseline at three months after the Day 1 injection. The record states that efficacy analyses were not performed and efficacy was not formally assessed because early termination affected data completeness. WOMAC function and pain outcomes by knee are also listed, with 6 outcome measures and 0 analyses recorded.
For safety, the registry reports 0 serious adverse events among 72 participants at risk, 2 participants with other adverse events among 72 at risk, and 0 deaths. These are descriptive counts from a single-group study, not comparative estimates.