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 Trial of CF101 to Treat Patients With Dry Eye Disease (NCT01235234), a randomized phase 3 study. The primary outcome is Number of Subjects Who Achieved Complete Clearing of Corneal Staining (i.e., Total Corneal FS Score = 0) at Week 24.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01235234 |
| Phase | Phase 3 |
| Condition | Keratoconjunctivitis Sicca |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 236 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Can-Fite BioPharma |
| Results posted | Yes |
2. Clinical Question
The clinical question is whether participants with moderate-to-severe dry eye disease assigned to oral CF101 differ from participants assigned to placebo on the recorded primary endpoint: complete clearing of corneal staining in the target eye at 24 weeks. The registry describes CF101 at 0.1 mg and 1 mg, with matching placebo as the comparator. The endpoint is a count of participants meeting the specified clearing criterion, rather than a reported average change in a continuous score.
The study also lists tear production and patient symptoms among its assessments. Secondary outcomes include the number of subjects with an increase in Schirmer Test tearing by >9 mm over baseline and the Ocular Surface Disease Index. These outcomes provide additional perspectives on tear production and symptoms, but their results are not reported in the registry record.
The primary efficacy population is identified as the ITT population, and the endpoint description says the count used NRI at 24 weeks. The registry record does not report the number meeting the primary endpoint in each group, a comparison between groups, or an uncertainty interval. Therefore, the clinical question is identifiable, but the posted record does not show an answer to it.
Population
Eligible patients with moderate-to-severe dry eye disease; the primary outcome description specifies the ITT population and a target eye.
Intervention
Oral CF101, randomized at 0.1 mg or 1 mg, twice daily for 24 weeks.
Comparator
Matching placebo, taken orally twice daily for 24 weeks.
Primary question
How many participants achieved complete clearing of corneal staining in the target eye at 24 weeks in each randomized group?
3. Trial Design
The registry describes a Phase 3, randomized, parallel-group, placebo-controlled, dose-finding study of daily oral CF101 in patients with moderate-to-severe dry eye disease. The record lists three arms: CF101 0.1 mg, CF101 1 mg, and matching placebo. Each assigned treatment was taken twice daily for 24 weeks. Enrollment is recorded as 236, and the trial status is completed.
The official title calls the study double-masked, while the registry’s masking classification is quadruple. These are the two descriptions recorded; the registry record does not explain how masking was implemented or which roles were included in its classification. Random allocation and a parallel-group model are recorded. The method used to generate or conceal the allocation sequence is not reported in the registry record.
The start is recorded as 2011-07 and primary completion as 2013-11. The study’s stated assessments included ocular surface integrity, tear production, and patient symptoms. The primary endpoint was complete clearing of corneal staining at 24 weeks. Listed secondary outcomes concern Schirmer Test tearing and the Ocular Surface Disease Index.
The record names Can-Fite BioPharma as sponsor. It does not report the number assigned to each arm in the trial-design information, the final number analyzed for each outcome, adherence, treatment discontinuations, or the statistical plan. Those details should not be inferred from the overall enrollment or from the descriptions of the arms.
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 | CF101 0.1 mg | CF101 1 mg | Placebo |
|---|---|---|---|
| STARTED | 77 | 78 | 81 |
| COMPLETED | 75 | 76 | 80 |
| NOT COMPLETED | 2 | 2 | 1 |
Reasons for not completing this period:
| Reason | CF101 0.1 mg | CF101 1 mg | Placebo |
|---|---|---|---|
| Adverse Event | 2 | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: The Number of Subjects Who Achieved Complete Clearing of Corneal Staining in Target Eye Using NRI at 24 weeks (ITT Population)
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 | CF101 0.1 mg | CF101 1 mg | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 77 | 78 | 81 | 236 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 57 | 56 | 59 | 172 |
| Age, Categorical: >=65 years | Participants | 20 | 22 | 22 | 64 |
| Age, Continuous | years | 56.8 (22 to 82) | 54.5 (19 to 90) | 55.1 (20 to 86) | 55.5 (19 to 90) |
| Sex: Female, Male: Female | Participants | 55 | 62 | 71 | 188 |
| Sex: Female, Male: Male | Participants | 22 | 16 | 10 | 48 |
| Region of Enrollment: Israel | participants | 77 | 78 | 81 | 236 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects Who Achieved Complete Clearing of Corneal Staining (i.e., Total Corneal FS Score = 0) at Week 24, measured over 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants who achieved complete clearing of corneal staining in the target eye at 24 weeks. The registry defines complete clearing as a total corneal fluorescein staining score of zero. The target eye was selected using the eye with the larger baseline corneal fluorescein staining value; if the baseline values were equal, the description specifies the eye with the larger central corneal staining value.
Corneal staining is an assessment of ocular surface integrity. A complete-clearing threshold turns the score into a binary outcome for each participant: the criterion is either met or not met. Reporting the number who meet it can make the endpoint straightforward to interpret, but the count alone is not enough to compare treatment groups. Group denominators and a treatment-effect estimate, with its uncertainty, are also needed for that comparison.
The endpoint is specified at 24 weeks and for the ITT population, with NRI named in the outcome description. The implementation of NRI is not reported in the registry record. Nor are the group-specific endpoint counts or a statistical comparison. Thus, the record defines what was intended to be counted, but does not provide the result needed to judge the magnitude or precision of a group difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the primary endpoint and the planned comparison, but does not report the primary endpoint counts. It therefore does not show how many participants in any arm achieved complete corneal-staining clearing at 24 weeks. No treatment-effect estimate, confidence interval, or p-value for that endpoint is reported in the registry record. The direction, size, and precision of a difference between CF101 and placebo cannot be described from these results.
This absence matters for interpretation. The endpoint is a count, but a raw count cannot be interpreted without its relevant denominator. Even with denominators, counts alone would not indicate how uncertain a group contrast is. A confidence interval, in general, describes a range of values compatible with the data and the method used; its width indicates precision. The registry record does not report such an interval for the primary outcome.
The record lists an ITT population and says the primary efficacy analysis used NRI. These labels identify aspects of the planned endpoint analysis, but they do not replace outcome results. The record does not state how NRI was implemented, how many observations were missing, or how missing observations were handled in practice. It also does not report the number analyzed in each arm.
Secondary outcomes include change in Schirmer Test tearing by the stated threshold and the Ocular Surface Disease Index. Their results are not reported in the registry record either. The study description mentions evaluations of ocular surface integrity, tear production, and symptoms, but that broad description is not evidence of a particular result on any of those measures.
The adverse-event information is separate from the efficacy endpoint. It records serious and other adverse-event counts by arm, along with selected serious-event terms and percentages. Those entries can describe what the registry lists for safety, but they do not fill in the missing efficacy comparison. Overall, the posted record permits a description of the study question and some safety counts, not a conclusion about the comparative primary outcome.
9. Statistical Methods Explained
The registry identifies a randomized, parallel-group design with CF101 dose groups and a placebo group. In general, randomization is intended to make assigned groups comparable, on average, with respect to measured and unmeasured baseline characteristics. It does not guarantee that every group will be balanced, and it does not remove the need to report how the allocation was performed or how participants were analyzed. The allocation-generation and concealment methods are not reported in the registry record.
What does the endpoint count?
The endpoint is binary at the participant level: complete clearing is achieved or it is not, according to the stated target-eye criterion. A binary endpoint can be presented as a count and, when the denominator is available, as a proportion. A comparison can then express a difference or another contrast between groups. The record reports the endpoint definition, but not group counts, denominators for this outcome, or a treatment-effect estimate. No comparison should be reconstructed without those inputs.
What does the target-eye rule contribute?
The registry specifies that the eye with the larger baseline corneal fluorescein staining value was selected as the target eye, with a central-staining rule for ties. Selecting an eye by a prespecified baseline rule can provide a consistent unit of assessment when the two eyes differ. The record does not describe any additional handling of eye-level measurements or give the eye-level results. The endpoint should therefore be interpreted as the registry’s participant-level count for the designated target eye, not as a summary of both eyes.
How should randomization and masking be read?
Randomization assigns participants to treatment groups by chance under a specified procedure. Masking is intended to reduce the influence of knowledge of assignment on care, measurement, or assessment. The record says randomized and gives both a double-masked description in the official title and a quadruple masking classification. It does not explain the masking roles or procedures. The parallel-group label means the record describes separate assigned groups rather than a crossover comparison; no further design detail should be inferred from that label.
What is an uncertainty interval?
In general, a confidence interval presents an estimate together with a range reflecting sampling uncertainty under its statistical method and assumptions. A narrow interval indicates greater precision than a wide interval, while neither interval alone establishes that a result is clinically important. Interpretation also depends on the endpoint, the comparison being made, and the analysis plan. No primary-outcome confidence interval or treatment-effect estimate is reported in the registry record, so its precision cannot be assessed.
What does NRI tell the reader?
The primary outcome description names NRI for the ITT population at 24 weeks. These are analysis labels, not a full account of the missing-data procedure. The registry record does not define the NRI implementation, report missingness by arm, or state how participants with unavailable endpoint assessments were classified. In general, assumptions about missing outcomes can affect a binary endpoint estimate; readers need the operational rule and missing-data information to assess that influence.
Why can multiplicity matter?
Multiplicity arises when a study makes several statistical comparisons or evaluates multiple outcomes. In general, repeated testing can increase the chance of at least one apparently notable result if no adjustment or hierarchy is used. The record lists a primary endpoint and secondary outcomes, but does not report a testing hierarchy, adjustment method, or full statistical analysis plan. No conclusion about multiplicity control is possible from the outcome list alone.
What is the role of a planning illustration?
In general, sample-size planning asks how much information a future study might need under stated assumptions about the effect to detect, allocation, significance level, and statistical method. The record’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it says the effect is a stated fraction of the observed effect. For time-to-event planning, it describes total events, and for other planning it describes participants per arm. Such calculations are planning illustrations, not observed power and not evidence of an observed treatment effect. The effect values and planning outputs are not reported in the registry record, so no numerical planning result can be interpreted from the information recorded.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary endpoint and lists secondary outcomes, but does not report a statistical testing hierarchy or a method for controlling multiplicity. In general, testing several outcomes or contrasts without a stated plan can make selective emphasis difficult to evaluate and can increase the chance of a seemingly notable result. The record does not establish whether any adjustment was used, so multiplicity control is not reported in the registry record.
The primary efficacy population is labeled ITT, and the endpoint description names NRI at 24 weeks. The record does not explain the NRI rule, identify how missing endpoint assessments were classified, or state whether any sensitivity analyses were performed. It also does not report missingness by group or the number included in the primary analysis. These omissions prevent assessment of how incomplete follow-up may have influenced the endpoint counts.
In general, an ITT analysis aims to analyze participants according to randomized assignment, but the label alone does not reveal the handling of unavailable outcome measurements or deviations from assigned treatment. The registry’s population label should not be treated as a complete analysis description. The statistical plan, analysis sets, and missing-data methods are not reported in the registry record.
Because outcome counts and comparative estimates are absent, the available information also cannot show whether the planned methods were followed or how robust the result was to alternative assumptions. No inference about the direction or reliability of an efficacy result is warranted from the population and method labels alone.
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 |
|---|---|---|---|
| CF101 0.1 mg | 6 | 77 | 7.8% |
| CF101 1 mg | 0 | 78 | 0.0% |
| Placebo | 1 | 81 | 1.2% |
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 |
|---|---|
| CF101 0.1 mg | 9 of 77 |
| CF101 1 mg | 13 of 78 |
| Placebo | 9 of 81 |
Most frequent serious adverse event terms
| Event term | Organ system | CF101 0.1 mg | CF101 1 mg | Placebo |
|---|---|---|---|---|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 1 of 77 | 0 of 78 | 0 of 81 |
| Facial nerve disorder | Nervous system disorders | 1 of 77 | 0 of 78 | 0 of 81 |
| Cerebral aneurysm ruptured syphilitic | Nervous system disorders | 1 of 77 | 0 of 78 | 0 of 81 |
| Endometrial cancer | Reproductive system and breast disorders | 1 of 77 | 0 of 78 | 0 of 81 |
| Cerebrovascular accident | Vascular disorders | 0 of 77 | 0 of 78 | 1 of 81 |
| Type 2 diabetes mellitus | Endocrine disorders | 1 of 77 | 0 of 78 | 0 of 81 |
| Hypertension | Vascular disorders | 1 of 77 | 0 of 78 | 0 of 81 |
| Angina unstable | Cardiac disorders | 1 of 77 | 0 of 78 | 0 of 81 |
Most frequent non-serious adverse event terms
| Event term | Organ system | CF101 0.1 mg | CF101 1 mg | Placebo |
|---|---|---|---|---|
| Urinary tract infection | Renal and urinary disorders | 9 of 77 | 13 of 78 | 9 of 81 |
Serious events with the highest arm-level rate: pneumonia (1.3%), facial nerve disorder (1.3%), cerebral aneurysm ruptured syphilitic (1.3%), endometrial cancer (1.3%), type 2 diabetes mellitus (1.3%).
The registry lists serious adverse-event counts for CF101 0.1 mg, CF101 1 mg, and placebo. The serious-event entries are 6 of 77, 0 of 78, and 1 of 81, respectively. It separately lists other adverse-event counts as 9 of 77, 13 of 78, and 9 of 81. These are registry counts, not comparative effect estimates, and no confidence intervals or statistical comparisons are reported in the registry record.
The selected serious-event terms are each listed with 1.3%: Pneumonia, Facial nerve disorder, Cerebral aneurysm ruptured syphilitic, Endometrial cancer, Type 2 diabetes mellitus, and Hypertension. The record does not provide enough detail alongside this list to establish an arm-specific comparison for each term. The deaths field is not populated; deaths are not reported in the registry record.
In general, adverse-event counts depend on the stated observation period, event definitions, and ascertainment. The registry record does not provide further detail about those elements or exposure-adjusted rates. The counts should be read as descriptive entries rather than proof of a causal relationship or a complete assessment of safety.
12. What the Result Does, and Does Not, Mean
The record means that a completed randomized Phase 3 study was registered to compare oral CF101 dose groups with matching placebo over 24 weeks in patients with moderate-to-severe dry eye disease. It specifies a primary endpoint based on complete clearing of corneal staining in a designated target eye and identifies an ITT population with NRI. Those details define the question and the intended outcome measure.
It does not mean that a comparative efficacy result can be determined from the posted results. Group-specific primary endpoint counts, an effect estimate, an uncertainty interval, and a p-value are not reported in the registry record. Without these, the direction, magnitude, and precision of the primary comparison are unknown from this record. The listed secondary outcomes likewise do not have results reported in the registry record.
The safety entries give descriptive counts and selected event terms, but they do not by themselves establish that an event was caused by treatment or support a full between-group safety comparison. The registry record does not report deaths. More complete interpretation would require outcome results and analysis details, including missing-data handling and the statistical plan; those details are not reported in the registry record.
In general, a registered trial design and an outcome definition are not substitutes for observed comparative results. The status completed indicates the trial’s recorded status, not that every planned result is available in the registry. Accordingly, the record supports a description of the study design, endpoint, and posted safety entries, but not a treatment-benefit conclusion.
13. Why This Trial Matters Statistically
This study is statistically notable for its combination of a randomized, parallel-group, dose-finding design and a binary primary endpoint. The endpoint translates corneal staining into whether complete clearing was achieved in the target eye at 24 weeks. That threshold is easy to state, but interpretation still requires the count and denominator in each group and a comparative estimate with its uncertainty.
The record also illustrates why an endpoint definition and a result are different kinds of information. It describes the target-eye selection rule, the ITT population, and NRI, yet does not report the primary outcome counts or the implementation of the missing-data method. A reader can identify the intended analysis question without being able to evaluate its answer.
Multiplicity and analysis-population details matter when a trial includes a primary outcome and additional outcomes. The registry lists secondary measures but does not report a testing hierarchy, adjustment approach, or complete statistical plan. The record therefore cannot show how the different outcome analyses were intended to relate to one another.
Finally, the planning description distinguishes assumptions for illustrative sample-size calculations from observed trial results. In general, planning calculations depend on assumptions and do not measure the power achieved after a trial. Here, no planning outputs or observed primary effect are reported in the registry record. The distinction is useful when interpreting any planning information associated with the trial: it cannot supply the missing efficacy estimate.
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 principal limitation of the registry record for interpreting efficacy is that it does not report the primary endpoint counts by group, the group denominators for that endpoint, or a treatment-effect estimate. It also does not report a confidence interval or p-value. Thus, neither the direction nor the precision of the primary comparison can be assessed. Results for the listed secondary outcomes are not reported in the registry record.
The record names the ITT population and NRI, but does not define the NRI procedure, describe missing endpoint assessments, or report analyses under alternative missing-data assumptions. It does not provide the number analyzed by group or explain how the primary analysis population was formed. These gaps limit assessment of the analysis and its sensitivity to missing observations.
Although randomization and masking are recorded, details of the allocation procedure and masking implementation are not reported in the registry record. The official title describes double masking, whereas the masking classification is quadruple; the record does not reconcile these descriptions. A statistical analysis plan, multiplicity approach, adherence information, and treatment discontinuation details are also not reported in the registry record.
The posted safety information is descriptive and lacks reported comparative estimates or uncertainty. The event observation period and further ascertainment details are not reported in the registry record. The selected serious-event terms do not provide enough context for a complete arm-specific assessment, and deaths are not reported. These limitations concern what can be concluded from the registry record, rather than establishing that the information was unavailable elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Trial of CF101 to Treat Patients With Dry Eye Disease — NCT01235234.
- Registry record last updated 2022-06-30; status last verified 2022-06.
- Results first posted 2015-03-11.
- 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 Phase 3 randomized, parallel-group, placebo-controlled, dose-finding study of oral CF101 in moderate-to-severe dry eye disease. The recorded arms are CF101 0.1 mg, CF101 1 mg, and matching placebo, each taken twice daily for 24 weeks. Enrollment is 236.
The primary endpoint is the number achieving complete clearing of corneal staining in the target eye at 24 weeks, with the primary analysis described for the ITT population using NRI. The registry record does not report the primary outcome counts, a treatment-effect estimate, or its precision. Secondary outcome results are also not reported in the registry record.
Descriptive serious and other adverse-event counts are recorded by arm, along with selected serious-event terms. The record does not report deaths. Details of the statistical plan, NRI implementation, missing-data handling, and multiplicity control are not reported in the registry record.