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 Evaluation of Efficacy of 20 µg/ml rhNGF New Formulation (With Anti-oxidant) in Patients With Stage 2 and 3 NK (NCT02227147), a randomized phase 2 study. The primary outcome is Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02227147 |
| Phase | Phase 2 |
| Condition | Neurotrophic Keratitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 48 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Dompé Farmaceutici S.p.A |
| Results posted | Yes |
2. Clinical Question
Population
People with stage 2 or stage 3 neurotrophic keratitis (NK). Stage 2 is described as a persistent epithelial defect, and stage 3 as a corneal ulcer. The primary endpoint population is described as the intention-to-treat population with last observation carried forward (LOCF), with an eligibility-related exclusion described for one randomized participant.
Intervention
rhNGF eye drops at 20 µg/ml, given 6 times a day. The formulation contains an anti-oxidant.
Comparator
Vehicle eye drops given 6 times a day. The vehicle formulation also contains an anti-oxidant, so the planned contrast is between rhNGF and a matched vehicle formulation rather than between drops and no treatment.
Primary question
At Week 8, what percentage of participants achieved complete healing of the persistent epithelial defect or corneal ulcer, as determined by a central reading center from corneal fluorescein staining of clinical pictures?
The clinical question is about complete healing at a prespecified assessment point, not just change in the appearance of the cornea. Healing was assessed centrally using clinical pictures and corneal fluorescein staining. The study description also identifies duration of complete healing, visual acuity, and corneal sensitivity as efficacy interests. These are related but distinct questions: reaching complete healing by Week 8 does not itself describe how long healing lasted, whether visual acuity changed, or whether corneal sensitivity improved.
The comparison is randomized, and both formulations contain an anti-oxidant. This design focuses the primary contrast on rhNGF versus vehicle under the study’s treatment conditions. The registry record does not report the arm-specific Week 8 healing percentages, an estimate of the difference between groups, or its uncertainty. Consequently, the clinical question can be specified from the record, but the posted results do not establish the direction or precision of the primary comparison.
3. Trial Design
The registry record describes a Phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel-group study. Its official title specifies an 8-week treatment period with a 24 or 32 Week Follow-up. The registered enrollment is 48, and the study status is completed. The sponsor is Dompé Farmaceutici S.p.A. The recorded study start is 2015-02 and primary completion is 2016-06.
Participants were assigned to rhNGF 20 µg/ml or vehicle. The rhNGF arm received eye drops containing rhNGF and an anti-oxidant; the vehicle arm received the anti-oxidant formulation without rhNGF. Both were described as given 6 times a day. The allocation was randomized, and the design was parallel-group, meaning the comparison was between assigned groups rather than a crossover in which participants received both formulations in sequence. The registry lists masking as quadruple and the official title describes the study as double-masked; the record does not explain the difference between those descriptions.
The main efficacy focus was complete healing of stage 2 or stage 3 NK by Week 8, assessed by a central reading center. The study description also refers to duration of healing, visual acuity, and corneal sensitivity. Listed secondary outcomes include investigator-defined healing, healing defined by both the central reading center and investigator, corneal clearing, visual acuity changes and gains, corneal sensitivity, and deterioration.
The registry record does not report the allocation sequence method, concealment procedures, the exact follow-up schedule for individual participants, or the reasons for the 24 or 32-week follow-up alternatives. It also does not report a statistical analysis plan or sample-size justification. The recorded enrollment should not be treated as the number included in every analysis: the primary endpoint description says one randomized participant had no post-baseline data and was excluded from the analysis.
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.
Controlled Treatment Period
| Stage | rhNGF 20 µg/ml | Vehicle |
|---|---|---|
| STARTED | 24 | 24 |
| COMPLETED | 18 | 21 |
| NOT COMPLETED | 6 | 3 |
Reasons for not completing this period:
| Reason | rhNGF 20 µg/ml | Vehicle |
|---|---|---|
| Adverse Event | 4 | 3 |
| Other | 2 | 0 |
Follow-up Period
| Stage | rhNGF 20 µg/ml | Vehicle |
|---|---|---|
| STARTED | 18 | 21 |
| COMPLETED | 15 | 16 |
| NOT COMPLETED | 3 | 5 |
Reasons for not completing this period:
| Reason | rhNGF 20 µg/ml | Vehicle |
|---|---|---|
| Other | 3 | 5 |
Analysis population for the primary outcome, as defined in the registry: ITT population, LOCF. One patient (randomized to rhNGF although not eligible) had no post-baseline data, was assumed to be missing, and was excluded from the analyses.
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: ITT population
| Characteristic | Unit | rhNGF 20 µg/ml | Vehicle | Total |
|---|---|---|---|---|
| Participants analysed | 24 | 24 | 48 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 11 | 13 | 24 |
| Age, Categorical: >=65 years | Participants | 13 | 11 | 24 |
| Age, Continuous | years | 65.9 (SD 13.85) | 54.5 (SD 14.15) | 65.2 (SD 13.87) |
| Sex: Female, Male: Female | Participants | 14 | 15 | 29 |
| Sex: Female, Male: Male | Participants | 10 | 9 | 19 |
| Region of Enrollment: United States | Participants | 24 | 24 | 48 |
6. Primary Endpoint
The registry lists the primary outcome as Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer, measured over Week 8.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with complete healing of a persistent epithelial defect or corneal ulcer at Week 8. The central reading center determined healing from clinical pictures using corneal fluorescein staining. The endpoint therefore reduces a clinical assessment to whether complete healing was achieved by a specified assessment time.
A binary endpoint such as this can be straightforward to interpret: each participant is classified as having or not having achieved the defined healing state at the assessment. A group percentage describes how often that state occurred in the analyzed participants. For a treatment comparison, the arm-specific percentages and a between-group estimate with an uncertainty interval would be needed to assess both the direction and precision of the contrast.
Central assessment is relevant because it applies a designated review process to the clinical pictures rather than relying only on each site investigator’s judgment. The registry also lists investigator-defined healing and an outcome combining central reading center and investigator definitions, which are related assessments but not identical endpoint definitions. The central-reader endpoint is the designated primary measure, so results from other definitions should not be substituted for it.
The endpoint captures complete healing at Week 8, but not the timing of healing before that visit or whether healing persisted afterward. Duration of complete healing is separately identified as an efficacy interest. The registry record does not report the primary endpoint’s arm-specific percentages, the treatment contrast, or a confidence interval, so the magnitude and precision of the primary result are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a primary efficacy question but does not report its numerical result. It gives the Week 8 endpoint definition and analysis population, yet no percentage achieving complete healing in either arm, no between-arm estimate, and no confidence interval or p-value. Without those results, the direction and size of the observed primary comparison cannot be described. There is also no basis in the registry record for judging how precisely the treatment contrast was estimated.
This distinction matters for a binary endpoint. The percentage in each arm would describe the observed frequency of complete healing under the study conditions. A between-arm estimate would describe the contrast, and a confidence interval would show the range of values reasonably compatible with the data under the analysis assumptions. A p-value, if reported, would address compatibility with a specified null hypothesis; it would not by itself show the size or clinical importance of a contrast. These are general statistical interpretations, not conclusions about this trial’s missing primary result.
The study record identifies the analysis population as ITT with LOCF. It also states that one participant randomized to rhNGF was not eligible, had no post-baseline data, was treated as missing, and was excluded from analyses. That detail is important when interpreting the stated analysis population: the label ITT does not mean that every randomized participant contributed to this endpoint analysis. The record does not give the arm-level analysis denominators or describe how the missing observation affected the endpoint estimate.
Other outcomes could inform different aspects of the study question, including investigator-defined healing, corneal clearing, visual acuity, corneal sensitivity, and deterioration. They cannot fill in the missing primary endpoint result unless their definitions and results directly address that primary question. The registry lists 8 outcome measures and 15 analyses, but does not report how the analyses were prioritized or whether adjustments were made for multiple comparisons.
Safety information is reported separately by treatment period and includes serious adverse event counts and deaths. Those counts are descriptive and have changing numbers at risk across periods. They should not be treated as a substitute for the primary efficacy comparison, and the available safety summaries alone do not establish a causal explanation for individual events.
Overall, the record allows readers to understand the trial question, endpoint, and some analysis details, but not the primary efficacy finding. The absence of reported primary results is not evidence that the groups were alike or different; it means the comparative estimate and its precision are not reported in the registry record.
9. Statistical Methods Explained
What does a percentage endpoint describe?
The primary endpoint is a binary outcome: complete healing is either recorded or not recorded for each participant at Week 8 under the central reading center’s definition. A percentage is a way to express the frequency of that outcome within an analyzed group. Comparing the two groups requires more than knowing that healing was assessed. The arm-specific percentages and a defined between-group contrast are needed to describe the observed result.
For a binary outcome, common contrasts include a difference between percentages or a ratio of percentages. Which contrast is used affects how the effect is expressed, but the registry record does not report the primary comparison or identify a primary effect measure. No such estimate should therefore be inferred from the endpoint description. General statistical principle: an estimate summarizes the observed contrast, while its uncertainty interval indicates how much uncertainty remains given the data and model assumptions.
Why does central assessment matter?
The primary endpoint was determined by a central reading center from clinical pictures, using corneal fluorescein staining. Central review can provide a common assessment process across participating centers. It does not eliminate all measurement uncertainty: pictures may vary in quality, and endpoint classifications can still be subject to interpretation. The registry record does not describe reviewer training, agreement between reviewers, or procedures for resolving disagreements.
Several other healing outcomes are listed, including investigator-defined healing and an outcome defined by both the central reading center and investigator. These outcomes may differ because they use different assessment sources or definitions. In general, an endpoint’s result is interpretable only in relation to its stated definition; results for one definition should not automatically be assumed to apply to another.
What is the role of masking and randomization?
Randomization is intended to make the assigned groups comparable, on average, with respect to factors that could affect outcomes. It does not guarantee balance in every characteristic in a particular trial. The record describes randomized allocation and lists masking as quadruple, while its official title says double-masked. It does not explain these different masking descriptions or provide operational details about who was masked. The record also does not describe the randomization sequence or allocation concealment.
Masking is generally used to reduce the influence of knowledge about assigned treatment on care, assessment, or reporting. Central review of pictures is a separate feature of endpoint assessment. Neither randomization nor masking can compensate for outcome results that are not reported; they describe design features, not the size or precision of the observed treatment contrast.
What can an uncertainty interval tell readers?
General explanation: a confidence interval expresses uncertainty around an estimated effect under a specified statistical procedure. A wide interval indicates that the estimate is compatible with a broad range of effects; a narrower interval indicates greater precision. The interval does not state the probability that a particular fixed effect is true. Interpreting it also requires knowing the effect measure, analysis population, and method used to construct it.
The registry record does not report a confidence interval for the primary endpoint, or the analysis method used to estimate one. It therefore does not permit a trial-specific assessment of precision. A reported percentage alone, even if available for each arm, would not fully describe uncertainty in the comparative effect.
Why can missing data and analysis choices matter?
The primary endpoint description names the ITT population with LOCF. LOCF means that a participant’s last observed value is carried forward to a later assessment when a later value is missing. General explanation: this approach can affect estimates because it substitutes an earlier observation for a missing later one. Whether that substitution is appropriate depends on why data are missing and how outcomes could change over time. The registry record does not report the missing-data assumptions or sensitivity analyses.
The record specifically notes that one participant randomized to rhNGF was not eligible, had no post-baseline data, was regarded as missing, and was excluded from analysis. This is a stated exception to a simple interpretation of ITT as including all randomized participants. The analysis denominators by arm and the handling of any other missing observations are not reported in the registry record.
What do the planning assumptions mean?
The sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These assumptions describe hypothetical future planning scenarios, not the trial’s own design rationale or an observed power calculation. The registry record does not report the original sample-size justification, and the planning illustrations should not be read as proof that the study had a particular probability of detecting an effect.
General explanation: over-dispersion occurs when outcome variability is greater than a statistical model assumes. It can make standard errors too small if ignored, leading to overconfident intervals or tests. This concept may matter in some outcome models, but the primary endpoint is described as a percentage and the registry record does not report a model or an over-dispersion assessment. No trial-specific claim about over-dispersion can be made from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 8 outcome measures and 15 analyses. The primary endpoint is complete healing at Week 8 as defined by the central reading center, but several secondary outcomes address other healing definitions, corneal clearing, visual acuity, corneal sensitivity, and deterioration. When several outcomes or analyses are examined, the chance of finding an apparently notable result by chance can increase. General statistical practice may address this through prespecified prioritization or multiplicity adjustment, but the registry record does not report whether either approach was used.
The statistical analysis plan, including the testing hierarchy and any adjustment for multiple comparisons, is not reported in the registry record. The record also does not identify which of the 15 analyses were confirmatory, exploratory, or otherwise prioritized. Therefore, any isolated result among secondary outcomes would need to be interpreted with caution and in the context of the analysis plan, which is not reported.
The primary endpoint population is described as ITT with LOCF. One participant randomized to rhNGF was not eligible, had no post-baseline data, was treated as missing, and was excluded from the analyses. The arm-level analysis denominators, the amount and pattern of any other missing data, and sensitivity analyses are not reported in the registry record.
LOCF carries the last observed value forward when a later measurement is missing. As a general matter, this requires assumptions about how an outcome would have changed after the last observation. The registry record does not state those assumptions or provide analyses using alternative missing-data methods. The stated analysis label and exclusion note therefore do not by themselves show how robust the findings were to missing-data choices. In this case, the primary result itself is not reported in the registry record, so the effect of missing-data decisions on its estimate cannot be assessed.
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 |
|---|---|---|---|
| rhNGF 20 µg/ml - Controlled Treatment Period | 4 | 23 | 17.4% |
| Vehicle - Controlled Treatment Period | 4 | 24 | 16.7% |
| rhNGF 20 µg/ml - Follow-up Period | 4 | 18 | 22.2% |
| Vehicle - Follow-up Period | 2 | 21 | 9.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| rhNGF 20 µg/ml - Controlled Treatment Period | 0 of 23 |
| Vehicle - Controlled Treatment Period | 0 of 24 |
| rhNGF 20 µg/ml - Follow-up Period | 5 of 18 |
| Vehicle - Follow-up Period | 2 of 21 |
| Uncontrolled Treatment Period | 0 of 13 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 4% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| rhNGF 20 µg/ml - Controlled Treatment Period | 21 of 23 |
| Vehicle - Controlled Treatment Period | 18 of 24 |
| rhNGF 20 µg/ml - Follow-up Period | 14 of 14 |
| Vehicle - Follow-up Period | 9 of 9 |
| Uncontrolled Treatment Period | 7 of 13 |
Most frequent serious adverse event terms
| Event term | Organ system | rhNGF 20 µg/ml - Controlled Treatment Period | Vehicle - Controlled Treatment Period | rhNGF 20 µg/ml - Follow-up Period | Vehicle - Follow-up Period | Uncontrolled Treatment Period |
|---|---|---|---|---|---|---|
| Disease Progression | General disorders | 1 of 23 | 2 of 24 | 0 of 18 | 0 of 21 | n/a of 0 |
| decreased visual acuity | Eye disorders | 0 of 23 | 1 of 24 | 1 of 18 | 1 of 21 | n/a of 0 |
| Corneal perforation | Eye disorders | 0 of 23 | 0 of 24 | 2 of 18 | 0 of 21 | n/a of 0 |
| Syncope | Nervous system disorders | 1 of 23 | 0 of 24 | 0 of 18 | 0 of 21 | n/a of 0 |
| Corneal Thinning | Eye disorders | 1 of 23 | 0 of 24 | 0 of 18 | 0 of 21 | n/a of 0 |
| Aqueous Humour Leakage | Injury, poisoning and procedural complications | 1 of 23 | 0 of 24 | 0 of 18 | 0 of 21 | n/a of 0 |
| ventral hernia | Gastrointestinal disorders | 0 of 23 | 1 of 24 | 0 of 18 | 0 of 21 | n/a of 0 |
| Death | General disorders | 0 of 23 | 0 of 24 | 1 of 18 | 0 of 21 | n/a of 0 |
| Disease recurrence | General disorders | 0 of 23 | 0 of 24 | 0 of 18 | 1 of 21 | n/a of 0 |
| Viral gastroenteritis | Infections and infestations | 0 of 23 | 0 of 24 | 1 of 18 | 0 of 21 | n/a of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | rhNGF 20 µg/ml - Controlled Treatment Period | Vehicle - Controlled Treatment Period | rhNGF 20 µg/ml - Follow-up Period | Vehicle - Follow-up Period | Uncontrolled Treatment Period |
|---|---|---|---|---|---|---|
| Eye pain | Eye disorders | 7 of 23 | 2 of 24 | 3 of 14 | 2 of 9 | 2 of 13 |
| Visual acuity reduced | Eye disorders | 5 of 23 | 5 of 24 | 1 of 14 | 2 of 9 | 2 of 13 |
| Corneal Epithelium Defect | Eye disorders | 3 of 23 | 2 of 24 | 2 of 14 | 1 of 9 | 0 of 13 |
| Lacrimation Increased | Eye disorders | 4 of 23 | 1 of 24 | 2 of 14 | 0 of 9 | 0 of 13 |
| Ocular Hyperaemia | Eye disorders | 4 of 23 | 1 of 24 | 0 of 14 | 2 of 9 | 0 of 13 |
| Intraocular Pressure Increased | Investigations | 3 of 23 | 2 of 24 | 2 of 14 | 0 of 9 | 0 of 13 |
| Disease Progression | General disorders | 2 of 23 | 4 of 24 | 0 of 14 | 0 of 9 | 0 of 13 |
| Eye Inflammation | Eye disorders | 3 of 23 | 2 of 24 | 0 of 14 | 0 of 9 | 0 of 13 |
| Eye Irritation | Eye disorders | 0 of 23 | 4 of 24 | 1 of 14 | 0 of 9 | 0 of 13 |
| Ocular Discomfort | Eye disorders | 2 of 23 | 2 of 24 | 1 of 14 | 0 of 9 | 0 of 13 |
Serious events with the highest arm-level rate: corneal perforation (11.1%), disease progression (8.3%), decreased visual acuity (5.6%), death (5.6%), viral gastroenteritis (5.6%).
The serious adverse event summaries are separated by treatment period. During the controlled treatment period, the rhNGF group had 4 participants with serious adverse events among 23 at risk; the vehicle group had 4 among 24 at risk. During follow-up, the rhNGF group had 4 participants with serious adverse events among 18 at risk, and the vehicle group had 2 among 21 at risk. In the uncontrolled treatment period, no participants were listed as at risk for serious adverse events and none were listed as affected.
The record lists 0 deaths in each controlled treatment group, 5 in the rhNGF follow-up group, 2 in the vehicle follow-up group, and 0 in the uncontrolled treatment period. These are counts recorded for the stated periods; they do not establish why deaths occurred or whether a treatment caused them. The serious adverse event terms listed include Corneal perforation (11.1%), Disease Progression (8.3%), decreased visual acuity (5.6%), Death (5.6%), Viral gastroenteritis (5.6%), and Disease recurrence (4.8%). The record does not give a treatment-group breakdown for these term percentages in the information available.
Numbers at risk vary across periods, so counts from different periods should not be compared as if they came from the same group size or follow-up exposure. The summaries are descriptive; interpretation would also require details such as event timing, participant-level histories, and attribution, which are not reported in the registry record. These safety counts do not replace the efficacy endpoint or establish a causal treatment effect.
12. What the Result Does, and Does Not, Mean
The study design addresses a specific question: whether complete healing of a persistent epithelial defect or corneal ulcer at Week 8 differed between participants assigned to rhNGF and those assigned to vehicle. The registry record provides the endpoint definition, treatment descriptions, and some analysis-population information. It does not report the primary endpoint percentages or a comparative estimate. As a result, it does not allow a reader to state whether the observed primary outcome favored either group, how large any contrast was, or how precise that contrast was.
This absence should not be mistaken for a finding of no difference, nor for evidence of a difference. Statistical interpretation depends on observed results and their uncertainty, neither of which is reported for the primary comparison. Even when a test result is available, statistical evidence and clinical importance are different questions: the size of an effect and its uncertainty are needed to evaluate the observed contrast in context.
The endpoint concerns complete healing at one assessment time. It does not, by itself, describe duration of healing, improvement in visual acuity, corneal sensitivity, or other listed outcomes. Those outcomes may add information about different aspects of the study, but their results and definitions must be considered separately. The record lists multiple outcome measures and analyses, while the analysis plan and multiplicity procedures are not reported.
The safety summaries report serious adverse events and deaths by period, with different numbers at risk across periods. They are descriptive counts rather than a complete account of event timing, attribution, or individual clinical circumstances. They should not be combined with the efficacy endpoint to infer a treatment effect.
The record supports a description of the trial’s question and structure, but not a conclusion about efficacy. A complete interpretation would require the primary results, arm-level denominators, an effect estimate and uncertainty interval, and the relevant analysis details. Those items are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for the way it defines a clinically assessed outcome and assigns its measurement. Complete healing at Week 8 is determined centrally from clinical pictures using corneal fluorescein staining. The record also lists investigator-defined healing and a combined central-reader and investigator definition, making clear that the assessment source and endpoint definition are relevant to interpretation. A result under one definition should not be treated as interchangeable with a result under another.
The randomized, parallel-group comparison uses a vehicle formulation that contains the same anti-oxidant formulation as the rhNGF drops. This makes the contrast more specific than a comparison with no drops, although the record does not provide enough design detail to assess all aspects of implementation. The official title describes double masking, while the record lists quadruple masking; the distinction is not explained.
Another important statistical issue is the gap between the clearly stated endpoint and the absent primary result. The registry specifies the assessment time, central method, and analysis population, but does not report the arm-specific healing percentages or comparative estimate. Without these, readers cannot judge effect size or precision. Transparent reporting of the estimate and its uncertainty is essential for interpreting a randomized comparison.
The record also notes LOCF and an eligibility-related exclusion despite describing the analysis population as ITT. This makes the handling of missing data and the exact analysis denominator relevant. The analysis plan, missing-data sensitivity analyses, and multiplicity procedures are not reported. These omissions limit assessment of how analysis choices might have influenced the reported outcomes.
Finally, safety summaries are organized by treatment period and have different numbers at risk. This is a useful reminder that event counts require their period and risk-set context. The record’s design details and safety summaries are informative, but they cannot replace unreported efficacy estimates or a transparent account of the 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.
The most direct limitation for interpreting efficacy is that the primary endpoint result is not reported in the registry record. There are no arm-specific Week 8 healing percentages, between-group estimate, confidence interval, or p-value. The effect’s direction, magnitude, and precision therefore cannot be evaluated from the record.
The enrollment listed is 48, but the primary analysis description says one participant randomized to rhNGF was not eligible, had no post-baseline data, and was excluded. The arm-specific analysis denominators and the handling of any other missing data are not reported. Although the endpoint population is labeled ITT with LOCF, the exact analysis set and the consequences of carrying observations forward cannot be fully assessed.
The record describes an 8-week treatment period and a 24 or 32 Week Follow-up, but does not explain the reason for the alternative follow-up durations or provide participant-level follow-up information. Safety groups have different numbers at risk across periods, so comparisons across periods are not straightforward. The uncontrolled treatment period also does not provide a concurrent randomized comparison.
Endpoint assessment has multiple listed definitions: central reading center, investigator, and a combined definition. The record does not report the central reviewers’ agreement, image-quality procedures, or how disagreements were resolved. It also does not explain the difference between the official title’s double-masked description and the masking field’s quadruple designation.
The analysis plan, sample-size justification, multiplicity procedures, and missing-data sensitivity analyses are not reported in the registry record. The study is Phase II and its registered enrollment is 48, but the record does not provide a rationale from which to assess whether the planned enrollment was adequate for the primary question. These limitations concern what can be evaluated from the record; they do not establish the direction or quality of the underlying trial findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of Efficacy of 20 µg/ml rhNGF New Formulation (With Anti-oxidant) in Patients With Stage 2 and 3 NK — NCT02227147.
- Registry record last updated 2022-12-08; status last verified 2022-12.
- Results first posted 2019-06-14.
- 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 II, multicenter, randomized, parallel-group study of rhNGF 20 µg/ml eye drops versus vehicle in stage 2 and 3 neurotrophic keratitis. Both formulations were given 6 times a day and contained an anti-oxidant. The official title describes an 8-week treatment period with a 24 or 32 Week Follow-up, and registered enrollment is 48.
The primary endpoint is complete healing at Week 8, determined by a central reading center from corneal fluorescein staining of clinical pictures. The endpoint population is described as ITT with LOCF, with one randomized, ineligible participant with no post-baseline data excluded from analysis. The registry also lists secondary efficacy outcomes and period-specific safety summaries.
The primary endpoint result, comparative estimate, and uncertainty are not reported in the registry record. The statistical plan, multiplicity procedures, and original sample-size justification are also not reported. The record therefore supports a description of the study design and analysis context, but not a conclusion about the primary efficacy comparison.