Retinitis Pigmentosa
Conditions
Keywords
Cone-Rod Degenerations, Cone-Rod Dystrophy, Cone-Rod Dystrophy 2, Cone-Rod Retinal Dystrophy, Pigmentary Retinopathy, Retinal Cone-Rod Dystrophy, Rod Cone Dystrophies, Rod-Cone Dystrophy, Tapetoretinal Degeneration
Brief summary
The primary objective of the study is to assess the safety and tolerability of two dose regimens of recombinant human nerve growth factor (rhNGF) eye drops solution administered over 6 months versus a vehicle control in patients with typical retinitis pigmentosa. The secondary objective of this study is to attempt to show a dose response by assessing the potential efficacy of the rhNGF dose regimens for improving or slowing the deterioration of visual function outcomes at 3 and 6 months. During a 6 month follow-up period patients will be monitored to determine if there is evidence of a persistent biological effect after discontinuation of the study treatment.
Detailed description
This is a 24-week phase Ib/II, multicenter, randomized, double-masked, vehicle controlled, parallel-group, dose-ranging study with a 24-week follow-up period to evaluate the safety and potential efficacy of two doses (60 μg/ml and 180 μg/ml) of recombinant human nerve growth factor (rhNGF) eye drops solution versus vehicle in patients with typical retinitis pigmentosa (RP).
Interventions
rhNGF 180 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes
DRUGrhNGF 60 µg/ml eye drops solution
rhNGF 60 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes
DRUGPlacebo
Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes
Sponsors
Dompé Farmaceutici S.p.A
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients 18 years of age or older. * Patients with typical forms of RP characterized by the following clinical features: classic fundus appearance (i.e. intraretinal pigment deposits, thinning and atrophy of the retinal pigment epithelium (RPE) in the mid- and far peripheral retina, with relative RPE preservation in the macula, waxy pallor of the optic disc, attenuation of the retinal vessels), reduced and delayed ERG responses, visual field constriction * Best corrected distance visual acuity (BCDVA) score of ≥ 48 ETDRS letters (equivalent to 20/100 Snellen, +0.7 LogMar, or 0.2 decimal fraction) in either eye at the time of study enrollment. * Documented evidence of disease progression within the 12 months prior to enrollment in the study as demonstrated by ERG (≥20% decrease in b wave amplitude in scotopic conditions or ≥25% in photopic conditions) and/or visual field testing (≥10% of Goldman Visual Field expressed as area square or ≥3 dB decrease of Humphrey Visual Field Mean Deviation). * Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her impartial witness must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent form signed by patients and/or impartial witness must have been approved by the Ethics Committee (IEC) for the current study. * Patients must have the ability and willingness to comply with study procedures.
Exclusion criteria
* Patients with atypical, early onset (first decade) or syndromic forms of RP (e.g. paravenous, pericentral sector or unilateral RP, Leber's congenital amaurosis, Refsum disease, Usher syndrome, Bardet-Biedl syndrome, etc). * Patients with non-recordable 30 Hz cone ERG in either eye. * Patients with Goldman visual field less than 20º using the V4e target or residual central visual field less than -35 dB as evaluated by the 24-2 program of the Humphrey visual field in either eye. * Evidence of an active ocular infection in either eye. * History of uveitis or evidence of intraocular inflammation in either eye. * History or evidence of glaucoma or an intraocular pressure (IOP) greater than or equal 21 mmHg in either eye at the time of study enrollment. * Patients with foveal thickness ≥ 250 micrometers (as evaluated with OCT). * History of cystoid macular oedema or presence of cystoid macular oedema on OCT at the time of study enrolment. * Anterior segment abnormalities or media opacities obscuring the view of the posterior pole in either eye. * History of any ocular surgery (including laser or refractive surgical procedures) in either eye within the 120 days before study enrolment. Ocular surgery will not be allowed during the study treatment period and elective ocular surgery procedures should not be planned during the duration of the follow-up period. * Treatment with corticosteroids (systemic, periocular or intravitreal) or any other non-approved, experimental, investigational or neuroprotectant therapy (systemic, topical, intravitreal) in either eye within 90 days of study enrollment. * Use of any medication other than the study medication for the treatment of ocular diseases with the exception of artificial tears during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of Anti-NGF Antibodies | At Day 0 and at week 24 | Anti-NGF antibodies tests were performed at screening and at the end of treatment |
| Number of Participants With Serious and Non-Serious Adverse Events | up to 48 weeks | Twenty-seven patients of the Safety population experienced at least one treatment-emergent adverse event, 11 patients in the rhNGF 60 μg/ml arm, 13 patients in the rhNGF 180 μg/ml arm and 3 patients in the vehicle arm. |
| Change in Ocular Tolerability - VAS | Weeks 1, 2, 6, 12, 24 | A global ocular discomfort score was determined using a 100 mm Visual Analogue Scale (VAS) on which 0 means no symptoms and 100 means the worst possible discomfort. Specific ocular symptoms to be assessed with the VAS included: foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia. For ocular tolerability analysis, mixed models for repeated measures were applied using various ocular tolerability parameters as response variable, treatment, visit and treatment by visit interaction as fixed effects, and baseline value as covariate. |
| Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Weeks 1, 2, 6, 12, 24, 36, 48 | Best-Corrected Distance Visual Acuity (BCDVA) was assessed for each eye at each visit using an ETDRS visual acuity chart at 4 meters. |
| Change in Intraocular Pressure (IOP) | Weeks 2,12 and 24 | Intraocular Pressure was measured using either Goldmann applanation tonometry or a handheld applanation tonometer (e.g. Tonopen) after the instillation of a topical anesthetic.IOP was assessed for each eye at day 0 and at week 2, 12 and 24 |
| Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0; Weeks 1, 2, 6, 12, 24, 36 and 48 | Slit Lamp Examination (SLE) (Biomicroscopy) was performed before the instillation of any dilating or anesthetic eye drops or fluorescein agents. SLE was executed to assess eyelids, lashes, conjunctiva, cornea, lens, iris and anterior chamber. |
| External Ocular Examination | Day 0, Weeks 1, 2, 6, 12, 24 | External ocular examinations were done to assess, for each eye and at each visit, the motility of extraocular muscles, appearance and function of the eyelids. |
| Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Day 0, Weeks 12, 24 and 48 | Dilated fundus ophthalmoscopy was assessed for each eye evaluating the retina, macula, choroid and optic nerve head. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Contrast Sensitivity | Weeks 12, 24, 36 and 48 | Contrast sensitivity was assessed using a Mars chart and is expressed as a log contrast sensitivity (log CS) score given by the log CS value at the lowest contrast numeral just prior to two incorrectly identified numerals, minus a scoring correction. The higher is the number of characters properly read by the patient, the higher is the contrast sensitivity. |
| Change From Baseline in Humphrey Visual Field 24-2 | Weeks 12, 24, 36 and 48 | The Humphrey Visual Field (HVF) analyzer is a tool for measuring the human visual field by providing information regarding the location of any disease processes or lesion(s) throughout the visual pathway. In particular, Humphrey Visual Field 24-2 was used to assess static perimetry by measuring 24 degrees temporally and 30 degrees nasally and tests 54 points. The Analyser projects a series of white light stimuli of varying intensities (brightness), throughout a uniformly illuminated bowl. The higher is the number of stimuli perceived by the patient, the better is the retina's ability to detect a stimulus at specific points within the visual field. |
| Change in Goldmann Visual Field | Weeks 12, 24, 36 and 48 | The Goldmann field exam was performed to assess kinetic perimetry on all enrolled patients. |
| Fundus Imaging | Day 0, Weeks 24 and 48 | A recordable fundus image (photo or other electronic format) showing the central 30 degrees was captured through a dilated pupil to document the appearance of the posterior pole. |
| Ocular Coherence Tomography (OCT) | Day 0, Weeks 12, 24, 36 and 48 | Ocular coherence tomography was performed to evaluate the cross-sectional anatomy of the macula and to document areas of retinal atrophy. |
| Microperimetry | Day 0, Weeks 12, 24, 36 and 48 | MP1 microperimetry was analyzed to provide a more accurate measurement of retinal sensitivity in the central visual field, even in patients with unstable or extrafoveal fixation. |
| Binocular Estermann Visual Field | Day 0, Weeks 12, 24, 36 and 48 | Binocular visual field with Estermann grid testing a stimulus array of 120 points spread over an area extending approximately ±75° horizontally, 35° superiorly and 55° inferiorly while the patient looked steadily at the fixation target. |
| Electrorethinogram (ERG) | Day 0, Weeks 12, 24, 36 and 48 | A full field and 30 Hz flicker ERG was performed according to international standards. Patients were treated with anesthetic and dilating drops prior to the ERG procedure. |
Countries
Italy
Participant flow
Pre-assignment details
Fifty patients were enrolled in the study. Two additional patients provided valid, written, informed consent but were not randomized due to screening failure. No study medication was administered to these patients.
Participants by arm
| Arm | Count |
|---|---|
| rhNGF 60µg/ml rhNGF 60 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes
rhNGF 60 µg/ml eye drops solution: rhNGF 60 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes | 20 |
| rhNGF 180 µg/ml rhNGF 180 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes.
rhNGF 180 µg/ml eye drops solution: rhNGF 180 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes | 20 |
| Vehicle Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes.
Placebo: Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes | 10 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | rhNGF 180 µg/ml | Vehicle | rhNGF 60µg/ml | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 10 Participants | 18 Participants | 48 Participants |
| Age, Continuous | 42.30 years STANDARD_DEVIATION 10.66 | 34.90 years STANDARD_DEVIATION 11.93 | 39.80 years STANDARD_DEVIATION 14.7 | 39.82 years STANDARD_DEVIATION 12.7 |
| Region of Enrollment Italy | 20 participants | 10 participants | 20 participants | 50 participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 14 Participants | 30 Participants |
| Sex: Female, Male Male | 11 Participants | 3 Participants | 6 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 10 |
| other Total, other adverse events | 11 / 20 | 13 / 20 | 3 / 10 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 | 0 / 10 |
Outcome results
Primary
Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart)
Best-Corrected Distance Visual Acuity (BCDVA) was assessed for each eye at each visit using an ETDRS visual acuity chart at 4 meters.
Time frame: Weeks 1, 2, 6, 12, 24, 36, 48
Population: Safety population: patients who received at least one dose of study medication. The safety population was used to analyze all safety endpoints (primary objective).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 1 vs Day 0 - right eye | 1.70 Letters read correctly | Standard Deviation 2.27 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 24 vs Day 0 - right eye | 2.71 Letters read correctly | Standard Deviation 3.16 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 6 vs Day 0 - right eye | 1.50 Letters read correctly | Standard Deviation 2.4 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 48 vs Day 0 - right eye | 1.60 Letters read correctly | Standard Deviation 4.96 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 24 vs Day 0 - left eye | 1.65 Letters read correctly | Standard Deviation 3.9 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 12 vs Day 0 - left eye | 2.25 Letters read correctly | Standard Deviation 3.64 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 2 vs Day 0 - left eye | 0.95 Letters read correctly | Standard Deviation 2.7 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 12 vs Day 0 - right eye | 1.85 Letters read correctly | Standard Deviation 2.23 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 1 vs Day 0 - left eye | 0.50 Letters read correctly | Standard Deviation 2.86 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 36 vs Day 0 - right eye | 2.15 Letters read correctly | Standard Deviation 3.99 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 2 vs Day 0 - right eye | 1.40 Letters read correctly | Standard Deviation 2.41 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 48 vs Day 0 - left eye | 0.15 Letters read correctly | Standard Deviation 5.32 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 36 vs Day 0 - left eye | 1.90 Letters read correctly | Standard Deviation 4.06 |
| rhNGF 60µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 6 vs Day 0 - left eye | 1.90 Letters read correctly | Standard Deviation 2.73 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 48 vs Day 0 - right eye | 1.37 Letters read correctly | Standard Deviation 6.99 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 1 vs Day 0 - left eye | 1.65 Letters read correctly | Standard Deviation 2.23 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 1 vs Day 0 - right eye | 2.20 Letters read correctly | Standard Deviation 3.29 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 2 vs Day 0 - left eye | 2.15 Letters read correctly | Standard Deviation 2.3 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 2 vs Day 0 - right eye | 2.55 Letters read correctly | Standard Deviation 4.24 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 6 vs Day 0 - left eye | 1.60 Letters read correctly | Standard Deviation 2.48 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 6 vs Day 0 - right eye | 3.25 Letters read correctly | Standard Deviation 4.56 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 12 vs Day 0 - left eye | 2.50 Letters read correctly | Standard Deviation 2.56 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 12 vs Day 0 - right eye | 2.50 Letters read correctly | Standard Deviation 4.47 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 24 vs Day 0 - left eye | 2.79 Letters read correctly | Standard Deviation 3.01 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 24 vs Day 0 - right eye | 3.89 Letters read correctly | Standard Deviation 5.52 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 36 vs Day 0 - left eye | 0.47 Letters read correctly | Standard Deviation 5.47 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 36 vs Day 0 - right eye | 2.74 Letters read correctly | Standard Deviation 6.62 |
| rhNGF 180 µg/ml | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 48 vs Day 0 - left eye | 0.26 Letters read correctly | Standard Deviation 5.02 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 6 vs Day 0 - left eye | 1.80 Letters read correctly | Standard Deviation 3.91 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 1 vs Day 0 - right eye | 1.70 Letters read correctly | Standard Deviation 3.2 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 24 vs Day 0 - right eye | 3.60 Letters read correctly | Standard Deviation 3.6 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 2 vs Day 0 - right eye | 2.60 Letters read correctly | Standard Deviation 3.6 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 48 vs Day 0 - left eye | -0.60 Letters read correctly | Standard Deviation 3.2 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 36 vs Day 0 - left eye | 0.33 Letters read correctly | Standard Deviation 3.28 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 2 vs Day 0 - left eye | 2.50 Letters read correctly | Standard Deviation 3.1 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 48 vs Day 0 - right eye | -1.00 Letters read correctly | Standard Deviation 5.21 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 12 vs Day 0 - left eye | 0.90 Letters read correctly | Standard Deviation 4.46 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 36 vs Day 0 - right eye | 0.89 Letters read correctly | Standard Deviation 3.3 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 12 vs Day 0 - right eye | 1.10 Letters read correctly | Standard Deviation 4.38 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 6 vs Day 0 - right eye | 2.00 Letters read correctly | Standard Deviation 3.27 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 1 vs Day 0 - left eye | 0.90 Letters read correctly | Standard Deviation 2.81 |
| Vehicle | Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) | Week 24 vs Day 0 - left eye | 2.20 Letters read correctly | Standard Deviation 3.97 |
Primary
Change in Intraocular Pressure (IOP)
Intraocular Pressure was measured using either Goldmann applanation tonometry or a handheld applanation tonometer (e.g. Tonopen) after the instillation of a topical anesthetic.IOP was assessed for each eye at day 0 and at week 2, 12 and 24
Time frame: Weeks 2,12 and 24
Population: Safety population: patients who received at least one dose of study medication. The safety population was used to analyze all safety endpoints (primary objective).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 60µg/ml | Change in Intraocular Pressure (IOP) | Week 24 vs Day 0 - left eye | -0.12 mmHg | Standard Deviation 2.03 |
| rhNGF 60µg/ml | Change in Intraocular Pressure (IOP) | Week 12 vs Day 0 - left eye | 0.55 mmHg | Standard Deviation 2.24 |
| rhNGF 60µg/ml | Change in Intraocular Pressure (IOP) | Week 24 vs Day 0 - right eye | 0.24 mmHg | Standard Deviation 2.54 |
| rhNGF 60µg/ml | Change in Intraocular Pressure (IOP) | Week 2 vs Day 0 - left eye | 0.15 mmHg | Standard Deviation 1.73 |
| rhNGF 60µg/ml | Change in Intraocular Pressure (IOP) | Week 12 vs Day 0 - right eye | 0.05 mmHg | Standard Deviation 2.06 |
| rhNGF 60µg/ml | Change in Intraocular Pressure (IOP) | Week 2 vs Day 0 - right eye | -0.15 mmHg | Standard Deviation 1.93 |
| rhNGF 180 µg/ml | Change in Intraocular Pressure (IOP) | Week 12 vs Day 0 - right eye | -0.25 mmHg | Standard Deviation 3.21 |
| rhNGF 180 µg/ml | Change in Intraocular Pressure (IOP) | Week 24 vs Day 0 - left eye | -0.21 mmHg | Standard Deviation 2.9 |
| rhNGF 180 µg/ml | Change in Intraocular Pressure (IOP) | Week 24 vs Day 0 - right eye | -0.53 mmHg | Standard Deviation 2.52 |
| rhNGF 180 µg/ml | Change in Intraocular Pressure (IOP) | Week 2 vs Day 0 - right eye | -0.40 mmHg | Standard Deviation 3.03 |
| rhNGF 180 µg/ml | Change in Intraocular Pressure (IOP) | Week 2 vs Day 0 - left eye | -0.70 mmHg | Standard Deviation 2.92 |
| rhNGF 180 µg/ml | Change in Intraocular Pressure (IOP) | Week 12 vs Day 0 - left eye | -0.45 mmHg | Standard Deviation 3.35 |
| Vehicle | Change in Intraocular Pressure (IOP) | Week 24 vs Day 0 - right eye | 0.90 mmHg | Standard Deviation 2.13 |
| Vehicle | Change in Intraocular Pressure (IOP) | Week 2 vs Day 0 - left eye | 0.30 mmHg | Standard Deviation 2.11 |
| Vehicle | Change in Intraocular Pressure (IOP) | Week 2 vs Day 0 - right eye | 0.70 mmHg | Standard Deviation 2.11 |
| Vehicle | Change in Intraocular Pressure (IOP) | Week 12 vs Day 0 - left eye | 0.70 mmHg | Standard Deviation 2.5 |
| Vehicle | Change in Intraocular Pressure (IOP) | Week 12 vs Day 0 - right eye | 1.20 mmHg | Standard Deviation 2.35 |
| Vehicle | Change in Intraocular Pressure (IOP) | Week 24 vs Day 0 - left eye | 0.00 mmHg | Standard Deviation 2.98 |
Primary
Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy
Dilated fundus ophthalmoscopy was assessed for each eye evaluating the retina, macula, choroid and optic nerve head.
Time frame: Day 0, Weeks 12, 24 and 48
Population: Safety population: all patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhNGF 60µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 12 - abnormal - left eye | 20 Participants |
| rhNGF 60µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 48 - abnormal - left eye | 17 Participants |
| rhNGF 60µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 24 - abnormal - left eye | 17 Participants |
| rhNGF 60µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 12 - abnormal - right eye | 20 Participants |
| rhNGF 60µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Day 0 - abnormal - left eye | 20 Participants |
| rhNGF 60µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Day 0 - abnormal - right eye | 20 Participants |
| rhNGF 60µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 48 - abnormal - right eye | 17 Participants |
| rhNGF 60µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 24 - abnormal - right eye | 17 Participants |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 12 - abnormal - right eye | 20 Participants |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Day 0 - abnormal - left eye | 20 Participants |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 24 - abnormal - right eye | 19 Participants |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Day 0 - abnormal - right eye | 20 Participants |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 12 - abnormal - left eye | 20 Participants |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 24 - abnormal - left eye | 19 Participants |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 48 - abnormal - left eye | 18 Participants |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 48 - abnormal - right eye | 18 Participants |
| Vehicle | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 24 - abnormal - left eye | 10 Participants |
| Vehicle | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Day 0 - abnormal - right eye | 10 Participants |
| Vehicle | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Day 0 - abnormal - left eye | 10 Participants |
| Vehicle | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 48 - abnormal - right eye | 10 Participants |
| Vehicle | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 48 - abnormal - left eye | 10 Participants |
| Vehicle | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 12 - abnormal - right eye | 10 Participants |
| Vehicle | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 12 - abnormal - left eye | 10 Participants |
| Vehicle | Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy | Week 24 - abnormal - right eye | 10 Participants |
Primary
Change in Ocular Tolerability - VAS
A global ocular discomfort score was determined using a 100 mm Visual Analogue Scale (VAS) on which 0 means no symptoms and 100 means the worst possible discomfort. Specific ocular symptoms to be assessed with the VAS included: foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia. For ocular tolerability analysis, mixed models for repeated measures were applied using various ocular tolerability parameters as response variable, treatment, visit and treatment by visit interaction as fixed effects, and baseline value as covariate.
Time frame: Weeks 1, 2, 6, 12, 24
Population: Safety population: patients who received at least one dose of study medication. The safety population was used to analyze all safety endpoints (primary objective).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 12 vs Day 0 | -0.75 units on a scale | Standard Deviation 19.49 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 2 vs Day 0 | -2.70 units on a scale | Standard Deviation 15.59 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 2 vs Day 0 | -1.15 units on a scale | Standard Deviation 24.92 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 6 vs Day 0 | 0.15 units on a scale | Standard Deviation 20.58 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 2 vs Day 0 | -2.50 units on a scale | Standard Deviation 13.81 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 1 vs Day 0 | -1.95 units on a scale | Standard Deviation 22.42 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 6 vs Day 0 | -0.50 units on a scale | Standard Deviation 19.99 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 6 vs Day 0 | -2.55 units on a scale | Standard Deviation 15.89 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 12 vs Day 0 | 2.65 units on a scale | Standard Deviation 8.22 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 2 vs Day 0 | -1.70 units on a scale | Standard Deviation 19.76 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 6 vs Day 0 | -2.60 units on a scale | Standard Deviation 14.41 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 1 vs Day 0 | 2.40 units on a scale | Standard Deviation 27.36 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 12 vs Day 0 | -3.30 units on a scale | Standard Deviation 18.94 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 2 vs Day 0 | -4.05 units on a scale | Standard Deviation 18.8 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 1 vs Day 0 | 2.25 units on a scale | Standard Deviation 23.87 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 12 vs Day 0 | -3.70 units on a scale | Standard Deviation 17.63 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 1 vs Day 0 | -2.35 units on a scale | Standard Deviation 23.33 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 24 vs Day 0 | 20.12 units on a scale | Standard Deviation 23.01 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 24 vs Day 0 | 2.24 units on a scale | Standard Deviation 19.81 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 12 vs Day 0 | 2.45 units on a scale | Standard Deviation 7.79 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 24 vs Day 0 | 22.94 units on a scale | Standard Deviation 26.6 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 24 vs Day 0 | 1.53 units on a scale | Standard Deviation 15.38 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 6 vs Day 0 | -7.10 units on a scale | Standard Deviation 23.16 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 12 vs Day 0 | 10.40 units on a scale | Standard Deviation 15.13 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 1 vs Day 0 | 29.95 units on a scale | Standard Deviation 27.99 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 24 vs Day 0 | -7.82 units on a scale | Standard Deviation 19.18 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 12 vs Day 0 | 12.60 units on a scale | Standard Deviation 16.21 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 1 vs Day 0 | 29.50 units on a scale | Standard Deviation 28.61 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 24 vs Day 0 | 3.35 units on a scale | Standard Deviation 10.57 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 6 vs Day 0 | 13.90 units on a scale | Standard Deviation 15.33 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 2 vs Day 0 | 23.45 units on a scale | Standard Deviation 27.07 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 12 vs Day 0 | -10.60 units on a scale | Standard Deviation 22.87 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 6 vs Day 0 | 14.10 units on a scale | Standard Deviation 15.49 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 2 vs Day 0 | 25.50 units on a scale | Standard Deviation 28.33 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 24 vs Day 0 | -9.35 units on a scale | Standard Deviation 19.89 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 24 vs Day 0 | 2.94 units on a scale | Standard Deviation 9.02 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 24 vs Day 0 | -11.88 units on a scale | Standard Deviation 29.02 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 12 vs Day 0 | -8.40 units on a scale | Standard Deviation 16.5 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 1 vs Day 0 | 4.60 units on a scale | Standard Deviation 18.75 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 1 vs Day 0 | 5.75 units on a scale | Standard Deviation 15.41 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 12 vs Day 0 | -8.20 units on a scale | Standard Deviation 15.62 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 1 vs Day 0 | 5.85 units on a scale | Standard Deviation 17.46 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 24 vs Day 0 | -12.12 units on a scale | Standard Deviation 28.23 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 6 vs Day 0 | -8.95 units on a scale | Standard Deviation 18.64 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 2 vs Day 0 | -0.15 units on a scale | Standard Deviation 10.46 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 2 vs Day 0 | 3.50 units on a scale | Standard Deviation 9.05 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 6 vs Day 0 | -10.50 units on a scale | Standard Deviation 20.67 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 2 vs Day 0 | 0.25 units on a scale | Standard Deviation 9.24 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 12 vs Day 0 | 6.25 units on a scale | Standard Deviation 18.54 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 2 vs Day 0 | -5.35 units on a scale | Standard Deviation 23.28 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 6 vs Day 0 | 4.75 units on a scale | Standard Deviation 19.63 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 2 vs Day 0 | -5.70 units on a scale | Standard Deviation 23.91 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 6 vs Day 0 | 5.60 units on a scale | Standard Deviation 18.53 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 12 vs Day 0 | -10.45 units on a scale | Standard Deviation 22.91 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 1 vs Day 0 | 5.45 units on a scale | Standard Deviation 15.23 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 2 vs Day 0 | 3.55 units on a scale | Standard Deviation 9.03 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 1 vs Day 0 | -10.50 units on a scale | Standard Deviation 27.01 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 12 vs Day 0 | 5.30 units on a scale | Standard Deviation 14 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 24 vs Day 0 | 20.35 units on a scale | Standard Deviation 31.59 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 1 vs Day 0 | -11.45 units on a scale | Standard Deviation 27.97 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 6 vs Day 0 | -6.50 units on a scale | Standard Deviation 22.84 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 24 vs Day 0 | 4.12 units on a scale | Standard Deviation 23.93 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 24 vs Day 0 | 14.82 units on a scale | Standard Deviation 21.97 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 6 vs Day 0 | 4.05 units on a scale | Standard Deviation 11.97 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 24 vs Day 0 | 3.53 units on a scale | Standard Deviation 22.8 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 1 vs Day 0 | 2.20 units on a scale | Standard Deviation 17.25 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 2 vs Day 0 | -3.40 units on a scale | Standard Deviation 17.72 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 12 vs Day 0 | -0.15 units on a scale | Standard Deviation 20.68 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 1 vs Day 0 | 2.25 units on a scale | Standard Deviation 16.18 |
| rhNGF 60µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 6 vs Day 0 | 4.05 units on a scale | Standard Deviation 13.62 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 1 vs Day 0 | -8.30 units on a scale | Standard Deviation 17.09 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 1 vs Day 0 | 4.80 units on a scale | Standard Deviation 21.31 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 6 vs Day 0 | 0.35 units on a scale | Standard Deviation 16.48 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 6 vs Day 0 | 0.20 units on a scale | Standard Deviation 8.33 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 1 vs Day 0 | 10.95 units on a scale | Standard Deviation 24.44 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 2 vs Day 0 | -0.90 units on a scale | Standard Deviation 13.78 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 2 vs Day 0 | 1.50 units on a scale | Standard Deviation 4.89 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 6 vs Day 0 | -0.50 units on a scale | Standard Deviation 9.32 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 6 vs Day 0 | 2.80 units on a scale | Standard Deviation 5.91 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 12 vs Day 0 | 3.05 units on a scale | Standard Deviation 15.14 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 12 vs Day 0 | 7.90 units on a scale | Standard Deviation 17.13 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 24 vs Day 0 | 6.32 units on a scale | Standard Deviation 21.14 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 24 vs Day 0 | 12.00 units on a scale | Standard Deviation 20.11 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 1 vs Day 0 | -3.75 units on a scale | Standard Deviation 18.43 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 1 vs Day 0 | 1.10 units on a scale | Standard Deviation 18.39 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 2 vs Day 0 | -3.70 units on a scale | Standard Deviation 20.13 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 2 vs Day 0 | -1.45 units on a scale | Standard Deviation 15.15 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 6 vs Day 0 | 4.65 units on a scale | Standard Deviation 19.59 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 12 vs Day 0 | 4.45 units on a scale | Standard Deviation 21.98 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 12 vs Day 0 | 8.95 units on a scale | Standard Deviation 22.77 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 24 vs Day 0 | 14.42 units on a scale | Standard Deviation 29.15 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 24 vs Day 0 | 17.79 units on a scale | Standard Deviation 26.13 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 1 vs Day 0 | -0.95 units on a scale | Standard Deviation 14.04 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 1 vs Day 0 | -0.25 units on a scale | Standard Deviation 12.72 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 2 vs Day 0 | -1.80 units on a scale | Standard Deviation 14.1 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 2 vs Day 0 | -1.05 units on a scale | Standard Deviation 12.59 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 6 vs Day 0 | -0.25 units on a scale | Standard Deviation 10.82 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 12 vs Day 0 | 3.00 units on a scale | Standard Deviation 16.91 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 12 vs Day 0 | 5.10 units on a scale | Standard Deviation 16.45 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 24 vs Day 0 | 7.00 units on a scale | Standard Deviation 19.05 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 24 vs Day 0 | 6.53 units on a scale | Standard Deviation 16.41 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 1 vs Day 0 | 26.70 units on a scale | Standard Deviation 23.91 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 1 vs Day 0 | 27.35 units on a scale | Standard Deviation 24.63 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 2 vs Day 0 | 18.30 units on a scale | Standard Deviation 23.2 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 2 vs Day 0 | 20.10 units on a scale | Standard Deviation 22.58 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 6 vs Day 0 | 20.25 units on a scale | Standard Deviation 24.56 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 6 vs Day 0 | 24.15 units on a scale | Standard Deviation 25.83 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 12 vs Day 0 | 18.50 units on a scale | Standard Deviation 20 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 12 vs Day 0 | 20.50 units on a scale | Standard Deviation 20.24 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 24 vs Day 0 | 33.74 units on a scale | Standard Deviation 27.72 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 24 vs Day 0 | 36.47 units on a scale | Standard Deviation 26.07 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 1 vs Day 0 | -1.40 units on a scale | Standard Deviation 8.68 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 1 vs Day 0 | -1.00 units on a scale | Standard Deviation 8.64 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 2 vs Day 0 | -2.35 units on a scale | Standard Deviation 9.53 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 2 vs Day 0 | -3.90 units on a scale | Standard Deviation 13.47 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 6 vs Day 0 | 0.75 units on a scale | Standard Deviation 5.19 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 6 vs Day 0 | 1.05 units on a scale | Standard Deviation 6.65 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 12 vs Day 0 | 2.30 units on a scale | Standard Deviation 12.81 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 12 vs Day 0 | 1.30 units on a scale | Standard Deviation 18.11 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 24 vs Day 0 | 1.47 units on a scale | Standard Deviation 13.75 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 24 vs Day 0 | 2.68 units on a scale | Standard Deviation 18.44 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 1 vs Day 0 | -12.45 units on a scale | Standard Deviation 24.46 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 2 vs Day 0 | -15.00 units on a scale | Standard Deviation 28.27 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 2 vs Day 0 | -13.70 units on a scale | Standard Deviation 24.75 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 6 vs Day 0 | -11.80 units on a scale | Standard Deviation 26.36 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 6 vs Day 0 | -11.55 units on a scale | Standard Deviation 22.53 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 12 vs Day 0 | -16.00 units on a scale | Standard Deviation 29.26 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 12 vs Day 0 | -14.70 units on a scale | Standard Deviation 27.66 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 24 vs Day 0 | -7.37 units on a scale | Standard Deviation 35.28 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 24 vs Day 0 | -8.32 units on a scale | Standard Deviation 31.21 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 1 vs Day 0 | -6.75 units on a scale | Standard Deviation 27.1 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 1 vs Day 0 | -7.15 units on a scale | Standard Deviation 27.21 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 2 vs Day 0 | -5.90 units on a scale | Standard Deviation 29.91 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 2 vs Day 0 | -5.60 units on a scale | Standard Deviation 29.66 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 6 vs Day 0 | -8.50 units on a scale | Standard Deviation 34.83 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 6 vs Day 0 | -6.25 units on a scale | Standard Deviation 36.89 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 12 vs Day 0 | -9.80 units on a scale | Standard Deviation 30.24 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 12 vs Day 0 | -10.00 units on a scale | Standard Deviation 29.69 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 24 vs Day 0 | -7.37 units on a scale | Standard Deviation 40.52 |
| rhNGF 180 µg/ml | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 24 vs Day 0 | -8.89 units on a scale | Standard Deviation 39.55 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 6 vs Day 0 | 5.10 units on a scale | Standard Deviation 7.19 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 1 vs Day 0 | 8.90 units on a scale | Standard Deviation 11.2 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 12 vs Day 0 | -8.70 units on a scale | Standard Deviation 19.86 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 12 vs Day 0 | 4.80 units on a scale | Standard Deviation 6.7 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 1 vs Day 0 | 5.60 units on a scale | Standard Deviation 9.2 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 1 vs Day 0 | 5.10 units on a scale | Standard Deviation 16.47 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 12 vs Day 0 | 5.50 units on a scale | Standard Deviation 8.32 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 24 vs Day 0 | 1.90 units on a scale | Standard Deviation 4.28 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 6 vs Day 0 | 1.70 units on a scale | Standard Deviation 4.69 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 24 vs Day 0 | 1.00 units on a scale | Standard Deviation 2.11 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 24 vs Day 0 | 1.80 units on a scale | Standard Deviation 3.82 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 1 vs Day 0 | 4.30 units on a scale | Standard Deviation 14.31 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 24 vs Day 0 | 1.00 units on a scale | Standard Deviation 2.11 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 12 vs Day 0 | 3.10 units on a scale | Standard Deviation 6.71 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 2 vs Day 0 | -1.60 units on a scale | Standard Deviation 9.02 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 1 vs Day 0 | 1.90 units on a scale | Standard Deviation 17.25 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 12 vs Day 0 | 3.30 units on a scale | Standard Deviation 6.63 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 6 vs Day 0 | 2.70 units on a scale | Standard Deviation 7.86 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 1 vs Day 0 | -0.70 units on a scale | Standard Deviation 12.27 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 6 vs Day 0 | 2.80 units on a scale | Standard Deviation 7.86 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 12 vs Day 0 | -7.40 units on a scale | Standard Deviation 17.77 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 2 vs Day 0 | 1.30 units on a scale | Standard Deviation 17.31 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 2 vs Day 0 | 2.00 units on a scale | Standard Deviation 6.32 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 2 vs Day 0 | -0.50 units on a scale | Standard Deviation 6.43 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 2 vs Day 0 | 1.60 units on a scale | Standard Deviation 14.98 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 2 vs Day 0 | 2.20 units on a scale | Standard Deviation 6.29 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 1 vs Day 0 | 3.50 units on a scale | Standard Deviation 11.07 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 6 vs Day 0 | -1.10 units on a scale | Standard Deviation 10.13 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Right eye, Wk 1 vs Day 0 | 0.10 units on a scale | Standard Deviation 0.32 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 6 vs Day 0 | -1.30 units on a scale | Standard Deviation 10.74 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 6 vs Day 0 | 0.20 units on a scale | Standard Deviation 8.26 |
| Vehicle | Change in Ocular Tolerability - VAS | Burning/Stinging - Left eye, Wk 1 vs Day 0 | 0.20 units on a scale | Standard Deviation 0.63 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 2 vs Day 0 | -0.20 units on a scale | Standard Deviation 0.63 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 12 vs Day 0 | 0.10 units on a scale | Standard Deviation 10.81 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 24 vs Day 0 | 0.30 units on a scale | Standard Deviation 1.77 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 2 vs Day 0 | 2.00 units on a scale | Standard Deviation 6.32 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 2 vs Day 0 | 2.00 units on a scale | Standard Deviation 6.32 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 24 vs Day 0 | -8.50 units on a scale | Standard Deviation 19.16 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 6 vs Day 0 | 0.00 units on a scale | Standard Deviation 0 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 1 vs Day 0 | 0.70 units on a scale | Standard Deviation 1.64 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 12 vs Day 0 | 0.70 units on a scale | Standard Deviation 7.7 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 6 vs Day 0 | 0.00 units on a scale | Standard Deviation 0 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 1 vs Day 0 | 0.80 units on a scale | Standard Deviation 1.62 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 24 vs Day 0 | 1.00 units on a scale | Standard Deviation 2.11 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 12 vs Day 0 | 3.00 units on a scale | Standard Deviation 6.75 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 24 vs Day 0 | 2.40 units on a scale | Standard Deviation 5.46 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Right eye, Wk 6 vs Day 0 | -1.70 units on a scale | Standard Deviation 10.27 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 12 vs Day 0 | 5.00 units on a scale | Standard Deviation 10.8 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 24 vs Day 0 | 3.00 units on a scale | Standard Deviation 6.75 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Left eye, Wk 24 vs Day 0 | -1.80 units on a scale | Standard Deviation 11.06 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Left eye, Wk 24 vs Day 0 | 1.00 units on a scale | Standard Deviation 3.16 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 12 vs Day 0 | 2.70 units on a scale | Standard Deviation 5.33 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 12 vs Day 0 | 0.50 units on a scale | Standard Deviation 1.58 |
| Vehicle | Change in Ocular Tolerability - VAS | Ocular pain - Right eye, Wk 24 vs Day 0 | 1.00 units on a scale | Standard Deviation 3.16 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 12 vs Day 0 | 3.60 units on a scale | Standard Deviation 7.43 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 2 vs Day 0 | 1.10 units on a scale | Standard Deviation 3.14 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 1 vs Day 0 | 4.90 units on a scale | Standard Deviation 6.51 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 6 vs Day 0 | 3.10 units on a scale | Standard Deviation 3.9 |
| Vehicle | Change in Ocular Tolerability - VAS | Blurred vision - Right eye, Wk 24 vs Day 0 | -1.30 units on a scale | Standard Deviation 7.01 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 1 vs Day 0 | 4.50 units on a scale | Standard Deviation 4.97 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 6 vs Day 0 | 3.90 units on a scale | Standard Deviation 4.43 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Left eye, Wk 12 vs Day 0 | 0.60 units on a scale | Standard Deviation 1.58 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 2 vs Day 0 | 4.60 units on a scale | Standard Deviation 6.87 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 24 vs Day 0 | -8.10 units on a scale | Standard Deviation 20.01 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Right eye, Wk 2 vs Day 0 | 4.50 units on a scale | Standard Deviation 6.85 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Right eye, Wk 2 vs Day 0 | 2.10 units on a scale | Standard Deviation 4.18 |
| Vehicle | Change in Ocular Tolerability - VAS | Photophobia - Left eye, Wk 1 vs Day 0 | 2.90 units on a scale | Standard Deviation 18.1 |
| Vehicle | Change in Ocular Tolerability - VAS | Sticky feeling - Left eye, Wk 6 vs Day 0 | 4.90 units on a scale | Standard Deviation 6.92 |
| Vehicle | Change in Ocular Tolerability - VAS | Itching - Left eye, Wk 2 vs Day 0 | 4.20 units on a scale | Standard Deviation 6.89 |
| Vehicle | Change in Ocular Tolerability - VAS | Foreign body sensation - Right eye, Wk 6 vs Day 0 | -0.20 units on a scale | Standard Deviation 0.63 |
Primary
External Ocular Examination
External ocular examinations were done to assess, for each eye and at each visit, the motility of extraocular muscles, appearance and function of the eyelids.
Time frame: Day 0, Weeks 1, 2, 6, 12, 24
Population: Safety population: all patients who received at least one dose of study medication. The safety population was used to analyze all safety endpoints (primary objective).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhNGF 60µg/ml | External Ocular Examination | Week 1 - abnormal - right eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 2 - normal - left eye | 20 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 24 - normal - left eye | 17 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 6 - normal - right eye | 20 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 2 - abnormal - left eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Day 0 - normal - right eye | 20 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 6 - abnormal - left eye | 1 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 2 - normal - right eye | 20 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Day 0 - normal - left eye | 20 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 6 - normal - left eye | 19 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 2 - abnormal - right eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 12 - abnormal - right eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Day 0 - abnormal - right eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 24 - abnormal - right eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 12 - normal - right eye | 20 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 1 - normal - left eye | 20 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 24 - abnormal - left eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 12 - abnormal - left eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 1 - abnormal - left eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Day 0 - abnormal - left eye | 0 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 12 - normal - left eye | 20 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 1 - normal - right eye | 20 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 24 - normal - right eye | 17 Participants |
| rhNGF 60µg/ml | External Ocular Examination | Week 6 - abnormal - right eye | 0 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 24 - abnormal - right eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Day 0 - normal - left eye | 19 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Day 0 - abnormal - left eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Day 0 - normal - right eye | 19 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Day 0 - abnormal - right eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 1 - normal - left eye | 19 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 1 - abnormal - left eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 1 - normal - right eye | 19 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 2 - normal - left eye | 19 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 2 - abnormal - left eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 2 - normal - right eye | 19 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 2 - abnormal - right eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 6 - normal - left eye | 19 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 6 - abnormal - left eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 6 - normal - right eye | 19 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 6 - abnormal - right eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 12 - normal - left eye | 19 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 12 - abnormal - left eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 12 - normal - right eye | 18 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 12 - abnormal - right eye | 2 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 24 - normal - left eye | 18 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 24 - abnormal - left eye | 1 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 24 - normal - right eye | 18 Participants |
| rhNGF 180 µg/ml | External Ocular Examination | Week 1 - abnormal - right eye | 1 Participants |
| Vehicle | External Ocular Examination | Week 6 - abnormal - right eye | 0 Participants |
| Vehicle | External Ocular Examination | Week 1 - abnormal - left eye | 0 Participants |
| Vehicle | External Ocular Examination | Day 0 - normal - left eye | 9 Participants |
| Vehicle | External Ocular Examination | Week 12 - normal - left eye | 10 Participants |
| Vehicle | External Ocular Examination | Week 1 - normal - left eye | 10 Participants |
| Vehicle | External Ocular Examination | Week 24 - normal - right eye | 10 Participants |
| Vehicle | External Ocular Examination | Week 12 - abnormal - left eye | 0 Participants |
| Vehicle | External Ocular Examination | Day 0 - abnormal - right eye | 0 Participants |
| Vehicle | External Ocular Examination | Week 24 - abnormal - left eye | 0 Participants |
| Vehicle | External Ocular Examination | Week 12 - normal - right eye | 10 Participants |
| Vehicle | External Ocular Examination | Day 0 - normal - right eye | 10 Participants |
| Vehicle | External Ocular Examination | Week 24 - abnormal - right eye | 0 Participants |
| Vehicle | External Ocular Examination | Week 2 - abnormal - right eye | 0 Participants |
| Vehicle | External Ocular Examination | Week 2 - normal - right eye | 10 Participants |
| Vehicle | External Ocular Examination | Week 12 - abnormal - right eye | 0 Participants |
| Vehicle | External Ocular Examination | Week 6 - normal - left eye | 10 Participants |
| Vehicle | External Ocular Examination | Week 2 - abnormal - left eye | 0 Participants |
| Vehicle | External Ocular Examination | Day 0 - abnormal - left eye | 1 Participants |
| Vehicle | External Ocular Examination | Week 6 - abnormal - left eye | 0 Participants |
| Vehicle | External Ocular Examination | Week 2 - normal - left eye | 10 Participants |
| Vehicle | External Ocular Examination | Week 1 - abnormal - right eye | 0 Participants |
| Vehicle | External Ocular Examination | Week 6 - normal - right eye | 10 Participants |
| Vehicle | External Ocular Examination | Week 1 - normal - right eye | 10 Participants |
| Vehicle | External Ocular Examination | Week 24 - normal - left eye | 10 Participants |
Primary
Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination
Slit Lamp Examination (SLE) (Biomicroscopy) was performed before the instillation of any dilating or anesthetic eye drops or fluorescein agents. SLE was executed to assess eyelids, lashes, conjunctiva, cornea, lens, iris and anterior chamber.
Time frame: Day 0; Weeks 1, 2, 6, 12, 24, 36 and 48
Population: s
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - normal - right eye | 8 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - normal - right eye | 14 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - abnormal - left eye | 9 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - abnormal - left eye | 8 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - abnormal - right eye | 9 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - abnormal - right eye | 6 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - normal - left eye | 13 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - abnormal - left eye | 7 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - normal - right eye | 14 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - normal - left eye | 13 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - abnormal - right eye | 6 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - normal - left eye | 13 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - abnormal - left eye | 7 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - normal - right eye | 14 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - abnormal - right eye | 6 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - normal - right eye | 14 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - normal - right eye | 13 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - abnormal - right eye | 6 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - normal - left eye | 11 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - abnormal - left eye | 7 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - normal - left eye | 12 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - abnormal - left eye | 9 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - abnormal - right eye | 7 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - normal - right eye | 12 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - abnormal - right eye | 8 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - normal - left eye | 11 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - normal - left eye | 13 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - abnormal - left eye | 9 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - abnormal - left eye | 7 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - normal - right eye | 12 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - abnormal - right eye | 8 Participants |
| rhNGF 60µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - normal - left eye | 8 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - normal - right eye | 14 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - normal - left eye | 12 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - normal - right eye | 15 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - abnormal - right eye | 6 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - abnormal - left eye | 7 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - normal - right eye | 14 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - normal - right eye | 13 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - abnormal - left eye | 10 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - abnormal - right eye | 5 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - abnormal - right eye | 6 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - normal - right eye | 14 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - abnormal - right eye | 6 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - normal - left eye | 11 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - abnormal - right eye | 6 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - normal - left eye | 13 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - abnormal - left eye | 8 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - abnormal - left eye | 7 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - normal - left eye | 12 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - normal - right eye | 11 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - abnormal - left eye | 7 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - normal - left eye | 10 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - abnormal - right eye | 8 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - abnormal - left eye | 8 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - normal - left eye | 12 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - abnormal - left eye | 7 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - abnormal - left eye | 6 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - abnormal - right eye | 8 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - normal - right eye | 12 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - normal - left eye | 14 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - normal - right eye | 12 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - abnormal - right eye | 7 Participants |
| rhNGF 180 µg/ml | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - normal - left eye | 13 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - abnormal - right eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - normal - left eye | 6 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - normal - left eye | 6 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - abnormal - right eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - normal - left eye | 6 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - abnormal - left eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - normal - right eye | 6 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Day 0 - abnormal - right eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - abnormal - left eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - normal - right eye | 6 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 1 - abnormal - right eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - abnormal - left eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - normal - right eye | 6 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 2 - abnormal - right eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - normal - left eye | 5 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - abnormal - left eye | 5 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - normal - right eye | 5 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 6 - abnormal - right eye | 5 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - normal - left eye | 6 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - abnormal - left eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - normal - right eye | 6 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 12 - abnormal - right eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - normal - left eye | 7 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - abnormal - left eye | 3 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - normal - right eye | 7 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 24 - abnormal - right eye | 3 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - normal - left eye | 5 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - abnormal - left eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 36 - normal - right eye | 5 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - normal - left eye | 6 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - abnormal - left eye | 4 Participants |
| Vehicle | Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination | Week 48 - normal - right eye | 6 Participants |
Primary
Number of Participants With Serious and Non-Serious Adverse Events
Twenty-seven patients of the Safety population experienced at least one treatment-emergent adverse event, 11 patients in the rhNGF 60 μg/ml arm, 13 patients in the rhNGF 180 μg/ml arm and 3 patients in the vehicle arm.
Time frame: up to 48 weeks
Population: Safety population: all patients who received at least one dose of study medication. The safety population was used to analyze all safety endpoints (primary objective).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhNGF 60µg/ml | Number of Participants With Serious and Non-Serious Adverse Events | 11 Participants |
| rhNGF 180 µg/ml | Number of Participants With Serious and Non-Serious Adverse Events | 13 Participants |
| Vehicle | Number of Participants With Serious and Non-Serious Adverse Events | 3 Participants |
Primary
Presence of Anti-NGF Antibodies
Anti-NGF antibodies tests were performed at screening and at the end of treatment
Time frame: At Day 0 and at week 24
Population: Safety population: all patients who received at least one dose of study medication. The safety population was used to analyze all safety endpoints (primary objective).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhNGF 60µg/ml | Presence of Anti-NGF Antibodies | Day 0 - absent | 20 Participants |
| rhNGF 60µg/ml | Presence of Anti-NGF Antibodies | Day 0 - missing | 0 Participants |
| rhNGF 60µg/ml | Presence of Anti-NGF Antibodies | Week 24 - absent | 20 Participants |
| rhNGF 60µg/ml | Presence of Anti-NGF Antibodies | Week 24 - missing | 0 Participants |
| rhNGF 180 µg/ml | Presence of Anti-NGF Antibodies | Week 24 - missing | 0 Participants |
| rhNGF 180 µg/ml | Presence of Anti-NGF Antibodies | Day 0 - absent | 20 Participants |
| rhNGF 180 µg/ml | Presence of Anti-NGF Antibodies | Week 24 - absent | 20 Participants |
| rhNGF 180 µg/ml | Presence of Anti-NGF Antibodies | Day 0 - missing | 0 Participants |
| Vehicle | Presence of Anti-NGF Antibodies | Week 24 - missing | 1 Participants |
| Vehicle | Presence of Anti-NGF Antibodies | Day 0 - missing | 1 Participants |
| Vehicle | Presence of Anti-NGF Antibodies | Week 24 - absent | 9 Participants |
| Vehicle | Presence of Anti-NGF Antibodies | Day 0 - absent | 9 Participants |
Secondary
Binocular Estermann Visual Field
Binocular visual field with Estermann grid testing a stimulus array of 120 points spread over an area extending approximately ±75° horizontally, 35° superiorly and 55° inferiorly while the patient looked steadily at the fixation target.
Time frame: Day 0, Weeks 12, 24, 36 and 48
Population: Intent to treat (ITT) population: all randomized patients. The ITT population was used for the exploratory analyses of ocular parameters.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhNGF 60µg/ml | Binocular Estermann Visual Field | Day 0 - normal | 1 Participants |
| rhNGF 60µg/ml | Binocular Estermann Visual Field | Day 0 - abnormal | 18 Participants |
| rhNGF 60µg/ml | Binocular Estermann Visual Field | Wk 12 - normal | 0 Participants |
| rhNGF 60µg/ml | Binocular Estermann Visual Field | Wk 12 - abnormal | 18 Participants |
| rhNGF 60µg/ml | Binocular Estermann Visual Field | Wk 24 - abnormal | 15 Participants |
| rhNGF 60µg/ml | Binocular Estermann Visual Field | Wk 36 - abnormal | 16 Participants |
| rhNGF 60µg/ml | Binocular Estermann Visual Field | Wk 48 - normal | 1 Participants |
| rhNGF 60µg/ml | Binocular Estermann Visual Field | Wk 48 - abnormal | 18 Participants |
| rhNGF 180 µg/ml | Binocular Estermann Visual Field | Wk 12 - normal | 2 Participants |
| rhNGF 180 µg/ml | Binocular Estermann Visual Field | Wk 48 - normal | 0 Participants |
| rhNGF 180 µg/ml | Binocular Estermann Visual Field | Wk 12 - abnormal | 17 Participants |
| rhNGF 180 µg/ml | Binocular Estermann Visual Field | Wk 24 - abnormal | 17 Participants |
| rhNGF 180 µg/ml | Binocular Estermann Visual Field | Wk 36 - abnormal | 15 Participants |
| rhNGF 180 µg/ml | Binocular Estermann Visual Field | Day 0 - normal | 2 Participants |
| rhNGF 180 µg/ml | Binocular Estermann Visual Field | Day 0 - abnormal | 18 Participants |
| rhNGF 180 µg/ml | Binocular Estermann Visual Field | Wk 48 - abnormal | 19 Participants |
| Vehicle | Binocular Estermann Visual Field | Wk 12 - normal | 1 Participants |
| Vehicle | Binocular Estermann Visual Field | Day 0 - abnormal | 8 Participants |
| Vehicle | Binocular Estermann Visual Field | Day 0 - normal | 2 Participants |
| Vehicle | Binocular Estermann Visual Field | Wk 12 - abnormal | 9 Participants |
| Vehicle | Binocular Estermann Visual Field | Wk 48 - normal | 1 Participants |
| Vehicle | Binocular Estermann Visual Field | Wk 36 - abnormal | 8 Participants |
| Vehicle | Binocular Estermann Visual Field | Wk 24 - abnormal | 8 Participants |
| Vehicle | Binocular Estermann Visual Field | Wk 48 - abnormal | 9 Participants |
Secondary
Change From Baseline in Contrast Sensitivity
Contrast sensitivity was assessed using a Mars chart and is expressed as a log contrast sensitivity (log CS) score given by the log CS value at the lowest contrast numeral just prior to two incorrectly identified numerals, minus a scoring correction. The higher is the number of characters properly read by the patient, the higher is the contrast sensitivity.
Time frame: Weeks 12, 24, 36 and 48
Population: Intent to treat (ITT) population: all randomized patients. The ITT population was used for the exploratory analyses of ocular parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 24 vs Day 0 - right eye | 0.03 score | Standard Deviation 0.11 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 12 vs Day 0 - right eye | 0.03 score | Standard Deviation 0.09 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 36 vs Day 0 - left eye | 0.04 score | Standard Deviation 0.16 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 36 vs Day 0 - binocular | 0.05 score | Standard Deviation 0.11 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 36 vs Day 0 - right eye | 0.06 score | Standard Deviation 0.12 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 24 vs Day 0 - binocular | 0.07 score | Standard Deviation 0.14 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 48 vs Day 0 - binocular | 0.04 score | Standard Deviation 0.12 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 12 vs Day 0 - left eye | 0.04 score | Standard Deviation 0.17 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 48 vs Day 0 - left eye | 0.08 score | Standard Deviation 0.15 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 24 vs Day 0 - left eye | 0.09 score | Standard Deviation 0.17 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 48 vs Day 0 - right eye | 0.02 score | Standard Deviation 0.12 |
| rhNGF 60µg/ml | Change From Baseline in Contrast Sensitivity | Wk 12 vs Day 0 - binocular | 0.05 score | Standard Deviation 0.14 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 48 vs Day 0 - right eye | -0.01 score | Standard Deviation 0.2 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 12 vs Day 0 - binocular | 0.03 score | Standard Deviation 0.1 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 12 vs Day 0 - left eye | 0.06 score | Standard Deviation 0.11 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 12 vs Day 0 - right eye | 0.01 score | Standard Deviation 0.17 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 24 vs Day 0 - binocular | 0.04 score | Standard Deviation 0.08 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 24 vs Day 0 - left eye | 0.06 score | Standard Deviation 0.13 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 36 vs Day 0 - binocular | -0.02 score | Standard Deviation 0.11 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 36 vs Day 0 - left eye | 0.00 score | Standard Deviation 0.16 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 36 vs Day 0 - right eye | -0.05 score | Standard Deviation 0.18 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 48 vs Day 0 - binocular | -0.03 score | Standard Deviation 0.18 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 48 vs Day 0 - left eye | -0.03 score | Standard Deviation 0.21 |
| rhNGF 180 µg/ml | Change From Baseline in Contrast Sensitivity | Wk 24 vs Day 0 - right eye | 0.03 score | Standard Deviation 0.14 |
Secondary
Change From Baseline in Humphrey Visual Field 24-2
The Humphrey Visual Field (HVF) analyzer is a tool for measuring the human visual field by providing information regarding the location of any disease processes or lesion(s) throughout the visual pathway. In particular, Humphrey Visual Field 24-2 was used to assess static perimetry by measuring 24 degrees temporally and 30 degrees nasally and tests 54 points. The Analyser projects a series of white light stimuli of varying intensities (brightness), throughout a uniformly illuminated bowl. The higher is the number of stimuli perceived by the patient, the better is the retina's ability to detect a stimulus at specific points within the visual field.
Time frame: Weeks 12, 24, 36 and 48
Population: Intent to treat (ITT) population: all randomized patients. The ITT population was used for the exploratory analyses of ocular parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 60µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 12 vs Day 0 - right eye | 1.09 dB | Standard Deviation 2.7 |
| rhNGF 60µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 12 vs Day 0 - left eye | 0.71 dB | Standard Deviation 2.23 |
| rhNGF 60µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 24 vs Day 0 - left eye | 1.33 dB | Standard Deviation 4.06 |
| rhNGF 60µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 24 vs Day 0 - right eye | 2.29 dB | Standard Deviation 3.95 |
| rhNGF 60µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 36 vs Day 0 - left eye | 1.18 dB | Standard Deviation 4.8 |
| rhNGF 60µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 36 vs Day 0 - right eye | 2.24 dB | Standard Deviation 4.73 |
| rhNGF 60µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 48 vs Day 0 - left eye | 1.08 dB | Standard Deviation 2.61 |
| rhNGF 60µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 48 vs Day 0 - right eye | 2.51 dB | Standard Deviation 5.29 |
| rhNGF 180 µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 24 vs Day 0 - left eye | 0.20 dB | Standard Deviation 1.48 |
| rhNGF 180 µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 48 vs Day 0 - left eye | -0.04 dB | Standard Deviation 1.12 |
| rhNGF 180 µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 24 vs Day 0 - right eye | 0.13 dB | Standard Deviation 1.25 |
| rhNGF 180 µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 36 vs Day 0 - left eye | -0.20 dB | Standard Deviation 0.97 |
| rhNGF 180 µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 36 vs Day 0 - right eye | -0.23 dB | Standard Deviation 1.11 |
| rhNGF 180 µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 12 vs Day 0 - left eye | 0.48 dB | Standard Deviation 0.92 |
| rhNGF 180 µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 12 vs Day 0 - right eye | 0.80 dB | Standard Deviation 2.53 |
| rhNGF 180 µg/ml | Change From Baseline in Humphrey Visual Field 24-2 | Wk 48 vs Day 0 - right eye | 0.13 dB | Standard Deviation 1.1 |
| Vehicle | Change From Baseline in Humphrey Visual Field 24-2 | Wk 24 vs Day 0 - left eye | -0.08 dB | Standard Deviation 0.75 |
| Vehicle | Change From Baseline in Humphrey Visual Field 24-2 | Wk 36 vs Day 0 - right eye | 1.06 dB | Standard Deviation 2.91 |
| Vehicle | Change From Baseline in Humphrey Visual Field 24-2 | Wk 12 vs Day 0 - right eye | 1.82 dB | Standard Deviation 3.2 |
| Vehicle | Change From Baseline in Humphrey Visual Field 24-2 | Wk 24 vs Day 0 - right eye | 0.45 dB | Standard Deviation 0.95 |
| Vehicle | Change From Baseline in Humphrey Visual Field 24-2 | Wk 48 vs Day 0 - left eye | -0.24 dB | Standard Deviation 1.13 |
| Vehicle | Change From Baseline in Humphrey Visual Field 24-2 | Wk 12 vs Day 0 - left eye | 0.53 dB | Standard Deviation 0.68 |
| Vehicle | Change From Baseline in Humphrey Visual Field 24-2 | Wk 36 vs Day 0 - left eye | -0.13 dB | Standard Deviation 1.01 |
| Vehicle | Change From Baseline in Humphrey Visual Field 24-2 | Wk 48 vs Day 0 - right eye | 0.12 dB | Standard Deviation 2.25 |
Secondary
Change in Goldmann Visual Field
The Goldmann field exam was performed to assess kinetic perimetry on all enrolled patients.
Time frame: Weeks 12, 24, 36 and 48
Population: Intent to treat (ITT) population: all randomized patients. The ITT population was used for the exploratory analyses of ocular parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 60µg/ml | Change in Goldmann Visual Field | Wk 36 vs Day 0 - left eye | 2.48 degrees | Standard Deviation 30.82 |
| rhNGF 60µg/ml | Change in Goldmann Visual Field | Wk 48 vs Day 0 - left eye | -1.79 degrees | Standard Deviation 36.98 |
| rhNGF 60µg/ml | Change in Goldmann Visual Field | Wk 36 vs Day 0 - right eye | -2.05 degrees | Standard Deviation 27.77 |
| rhNGF 60µg/ml | Change in Goldmann Visual Field | Wk 12 vs Day 0 - right eye | 8.20 degrees | Standard Deviation 20.37 |
| rhNGF 60µg/ml | Change in Goldmann Visual Field | Wk 48 vs Day 0 - right eye | -5.04 degrees | Standard Deviation 28.34 |
| rhNGF 60µg/ml | Change in Goldmann Visual Field | Wk 24 vs Day 0 - left eye | 6.47 degrees | Standard Deviation 45.9 |
| rhNGF 60µg/ml | Change in Goldmann Visual Field | Wk 12 vs Day 0 - left eye | 11.56 degrees | Standard Deviation 27.48 |
| rhNGF 60µg/ml | Change in Goldmann Visual Field | Wk 24 vs Day 0 - right eye | -4.67 degrees | Standard Deviation 35.67 |
| rhNGF 180 µg/ml | Change in Goldmann Visual Field | Wk 36 vs Day 0 - left eye | -6.57 degrees | Standard Deviation 28.81 |
| rhNGF 180 µg/ml | Change in Goldmann Visual Field | Wk 24 vs Day 0 - right eye | 2.00 degrees | Standard Deviation 27.95 |
| rhNGF 180 µg/ml | Change in Goldmann Visual Field | Wk 24 vs Day 0 - left eye | 10.08 degrees | Standard Deviation 21.02 |
| rhNGF 180 µg/ml | Change in Goldmann Visual Field | Wk 36 vs Day 0 - right eye | -11.94 degrees | Standard Deviation 27.85 |
| rhNGF 180 µg/ml | Change in Goldmann Visual Field | Wk 48 vs Day 0 - left eye | -13.76 degrees | Standard Deviation 29.37 |
| rhNGF 180 µg/ml | Change in Goldmann Visual Field | Wk 12 vs Day 0 - left eye | 1.27 degrees | Standard Deviation 14.53 |
| rhNGF 180 µg/ml | Change in Goldmann Visual Field | Wk 48 vs Day 0 - right eye | -14.49 degrees | Standard Deviation 25.38 |
| rhNGF 180 µg/ml | Change in Goldmann Visual Field | Wk 12 vs Day 0 - right eye | 3.34 degrees | Standard Deviation 16.37 |
| Vehicle | Change in Goldmann Visual Field | Wk 48 vs Day 0 - right eye | 6.84 degrees | Standard Deviation 44.01 |
| Vehicle | Change in Goldmann Visual Field | Wk 12 vs Day 0 - left eye | 14.21 degrees | Standard Deviation 22.92 |
| Vehicle | Change in Goldmann Visual Field | Wk 12 vs Day 0 - right eye | 1.28 degrees | Standard Deviation 25.03 |
| Vehicle | Change in Goldmann Visual Field | Wk 24 vs Day 0 - left eye | 15.08 degrees | Standard Deviation 41.63 |
| Vehicle | Change in Goldmann Visual Field | Wk 24 vs Day 0 - right eye | 16.14 degrees | Standard Deviation 43.97 |
| Vehicle | Change in Goldmann Visual Field | Wk 36 vs Day 0 - left eye | 2.37 degrees | Standard Deviation 24.26 |
| Vehicle | Change in Goldmann Visual Field | Wk 48 vs Day 0 - left eye | 6.40 degrees | Standard Deviation 42.15 |
| Vehicle | Change in Goldmann Visual Field | Wk 36 vs Day 0 - right eye | 0.67 degrees | Standard Deviation 25.78 |
Secondary
Electrorethinogram (ERG)
A full field and 30 Hz flicker ERG was performed according to international standards. Patients were treated with anesthetic and dilating drops prior to the ERG procedure.
Time frame: Day 0, Weeks 12, 24, 36 and 48
Population: Intent to treat (ITT) population: all randomized patients. The ITT population was used for the exploratory analyses of ocular parameters.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Day 0 - abnormal - left eye | 20 Participants |
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Wk 36 - abnormal - right eye | 18 Participants |
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Wk 12 - abnormal - right eye | 18 Participants |
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Wk 48 - abnormal - right eye | 20 Participants |
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Wk 36 - abnormal - left eye | 18 Participants |
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Wk 24 - abnormal - right eye | 17 Participants |
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Day 0 - abnormal - right eye | 20 Participants |
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Wk 24 - abnormal - left eye | 17 Participants |
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Wk 48 - abnormal - left eye | 20 Participants |
| rhNGF 60µg/ml | Electrorethinogram (ERG) | Wk 12 - abnormal - left eye | 18 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Wk 48 - abnormal - right eye | 19 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Day 0 - abnormal - left eye | 20 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Wk 24 - abnormal - left eye | 19 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Day 0 - abnormal - right eye | 20 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Wk 12 - abnormal - left eye | 20 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Wk 12 - abnormal - right eye | 20 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Wk 24 - abnormal - right eye | 19 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Wk 36 - abnormal - left eye | 19 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Wk 36 - abnormal - right eye | 19 Participants |
| rhNGF 180 µg/ml | Electrorethinogram (ERG) | Wk 48 - abnormal - left eye | 19 Participants |
| Vehicle | Electrorethinogram (ERG) | Wk 48 - abnormal - left eye | 10 Participants |
| Vehicle | Electrorethinogram (ERG) | Wk 36 - abnormal - left eye | 9 Participants |
| Vehicle | Electrorethinogram (ERG) | Wk 12 - abnormal - left eye | 10 Participants |
| Vehicle | Electrorethinogram (ERG) | Day 0 - abnormal - left eye | 10 Participants |
| Vehicle | Electrorethinogram (ERG) | Wk 36 - abnormal - right eye | 9 Participants |
| Vehicle | Electrorethinogram (ERG) | Day 0 - abnormal - right eye | 10 Participants |
| Vehicle | Electrorethinogram (ERG) | Wk 24 - abnormal - left eye | 10 Participants |
| Vehicle | Electrorethinogram (ERG) | Wk 48 - abnormal - right eye | 10 Participants |
| Vehicle | Electrorethinogram (ERG) | Wk 24 - abnormal - right eye | 10 Participants |
| Vehicle | Electrorethinogram (ERG) | Wk 12 - abnormal - right eye | 10 Participants |
Secondary
Fundus Imaging
A recordable fundus image (photo or other electronic format) showing the central 30 degrees was captured through a dilated pupil to document the appearance of the posterior pole.
Time frame: Day 0, Weeks 24 and 48
Population: Intent to treat (ITT) population: all randomized patients. The ITT population was used for the exploratory analyses of ocular parameters.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhNGF 60µg/ml | Fundus Imaging | Day 0 - abnormal - left eye | 18 Participants |
| rhNGF 60µg/ml | Fundus Imaging | Day 0 - normal - right eye | 1 Participants |
| rhNGF 60µg/ml | Fundus Imaging | Wk 24 - abnormal - left eye | 16 Participants |
| rhNGF 60µg/ml | Fundus Imaging | Day 0 - abnormal - right eye | 18 Participants |
| rhNGF 60µg/ml | Fundus Imaging | Wk 48 - abnormal - left eye | 17 Participants |
| rhNGF 60µg/ml | Fundus Imaging | Day 0 - normal - left eye | 1 Participants |
| rhNGF 60µg/ml | Fundus Imaging | Wk 48 - abnormal - right eye | 17 Participants |
| rhNGF 60µg/ml | Fundus Imaging | Wk 24 - abnormal - right eye | 16 Participants |
| rhNGF 180 µg/ml | Fundus Imaging | Day 0 - abnormal - right eye | 19 Participants |
| rhNGF 180 µg/ml | Fundus Imaging | Day 0 - abnormal - left eye | 19 Participants |
| rhNGF 180 µg/ml | Fundus Imaging | Day 0 - normal - left eye | 0 Participants |
| rhNGF 180 µg/ml | Fundus Imaging | Day 0 - normal - right eye | 0 Participants |
| rhNGF 180 µg/ml | Fundus Imaging | Wk 24 - abnormal - left eye | 19 Participants |
| rhNGF 180 µg/ml | Fundus Imaging | Wk 24 - abnormal - right eye | 19 Participants |
| rhNGF 180 µg/ml | Fundus Imaging | Wk 48 - abnormal - left eye | 18 Participants |
| rhNGF 180 µg/ml | Fundus Imaging | Wk 48 - abnormal - right eye | 18 Participants |
| Vehicle | Fundus Imaging | Day 0 - normal - right eye | 0 Participants |
| Vehicle | Fundus Imaging | Wk 24 - abnormal - right eye | 9 Participants |
| Vehicle | Fundus Imaging | Day 0 - abnormal - right eye | 10 Participants |
| Vehicle | Fundus Imaging | Wk 48 - abnormal - right eye | 10 Participants |
| Vehicle | Fundus Imaging | Day 0 - abnormal - left eye | 10 Participants |
| Vehicle | Fundus Imaging | Wk 48 - abnormal - left eye | 10 Participants |
| Vehicle | Fundus Imaging | Wk 24 - abnormal - left eye | 9 Participants |
| Vehicle | Fundus Imaging | Day 0 - normal - left eye | 0 Participants |
Secondary
Microperimetry
MP1 microperimetry was analyzed to provide a more accurate measurement of retinal sensitivity in the central visual field, even in patients with unstable or extrafoveal fixation.
Time frame: Day 0, Weeks 12, 24, 36 and 48
Population: Intent to treat (ITT) population: all randomized patients. The ITT population was used for the exploratory analyses of ocular parameters.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhNGF 60µg/ml | Microperimetry | Wk 48 - normal - left eye | 1 Participants |
| rhNGF 60µg/ml | Microperimetry | Day 0 - normal - left eye | 1 Participants |
| rhNGF 60µg/ml | Microperimetry | Wk 36 - normal - left eye | 0 Participants |
| rhNGF 60µg/ml | Microperimetry | Week 12 - normal - right eye | 2 Participants |
| rhNGF 60µg/ml | Microperimetry | Week 12 - abnormal - left eye | 15 Participants |
| rhNGF 60µg/ml | Microperimetry | Wk 24 - abnormal - right eye | 13 Participants |
| rhNGF 60µg/ml | Microperimetry | Week 12 - abnormal - right eye | 13 Participants |
| rhNGF 60µg/ml | Microperimetry | Wk 48 - normal - right eye | 1 Participants |
| rhNGF 60µg/ml | Microperimetry | Wk 24 - abnormal - left eye | 14 Participants |
| rhNGF 60µg/ml | Microperimetry | Week 24 - normal - left eye | 0 Participants |
| rhNGF 60µg/ml | Microperimetry | Day 0 - abnormal - left eye | 17 Participants |
| rhNGF 60µg/ml | Microperimetry | Wk 24 - normal - right eye | 1 Participants |
| rhNGF 60µg/ml | Microperimetry | Wk 48 - abnormal - left eyew | 19 Participants |
| rhNGF 60µg/ml | Microperimetry | Day 0 - normal - right eye | 2 Participants |
| rhNGF 60µg/ml | Microperimetry | Week 36 - abnormal - right eye | 19 Participants |
| rhNGF 60µg/ml | Microperimetry | Wk 36 - normal - right eye | 0 Participants |
| rhNGF 60µg/ml | Microperimetry | Day 0 - abnormal - right eye | 16 Participants |
| rhNGF 60µg/ml | Microperimetry | Wk 48 - abnormal - right eye | 19 Participants |
| rhNGF 60µg/ml | Microperimetry | Wk 36 - abnormal - left eye | 19 Participants |
| rhNGF 60µg/ml | Microperimetry | Week 12 - normal - left eye | 0 Participants |
| rhNGF 180 µg/ml | Microperimetry | Day 0 - normal - right eye | 2 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 24 - normal - right eye | 2 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 48 - abnormal - left eyew | 18 Participants |
| rhNGF 180 µg/ml | Microperimetry | Day 0 - normal - left eye | 1 Participants |
| rhNGF 180 µg/ml | Microperimetry | Day 0 - abnormal - left eye | 18 Participants |
| rhNGF 180 µg/ml | Microperimetry | Day 0 - abnormal - right eye | 17 Participants |
| rhNGF 180 µg/ml | Microperimetry | Week 12 - normal - left eye | 1 Participants |
| rhNGF 180 µg/ml | Microperimetry | Week 12 - abnormal - left eye | 13 Participants |
| rhNGF 180 µg/ml | Microperimetry | Week 12 - normal - right eye | 1 Participants |
| rhNGF 180 µg/ml | Microperimetry | Week 12 - abnormal - right eye | 13 Participants |
| rhNGF 180 µg/ml | Microperimetry | Week 24 - normal - left eye | 1 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 24 - abnormal - left eye | 17 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 24 - abnormal - right eye | 16 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 36 - normal - left eye | 2 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 36 - abnormal - left eye | 15 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 36 - normal - right eye | 1 Participants |
| rhNGF 180 µg/ml | Microperimetry | Week 36 - abnormal - right eye | 16 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 48 - normal - left eye | 1 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 48 - normal - right eye | 1 Participants |
| rhNGF 180 µg/ml | Microperimetry | Wk 48 - abnormal - right eye | 18 Participants |
| Vehicle | Microperimetry | Day 0 - abnormal - left eye | 9 Participants |
| Vehicle | Microperimetry | Wk 36 - normal - left eye | 1 Participants |
| Vehicle | Microperimetry | Day 0 - abnormal - right eye | 9 Participants |
| Vehicle | Microperimetry | Day 0 - normal - left eye | 1 Participants |
| Vehicle | Microperimetry | Wk 36 - abnormal - left eye | 8 Participants |
| Vehicle | Microperimetry | Day 0 - normal - right eye | 1 Participants |
| Vehicle | Microperimetry | Wk 48 - abnormal - right eye | 9 Participants |
| Vehicle | Microperimetry | Wk 36 - normal - right eye | 0 Participants |
| Vehicle | Microperimetry | Week 12 - normal - left eye | 1 Participants |
| Vehicle | Microperimetry | Wk 48 - normal - right eye | 1 Participants |
| Vehicle | Microperimetry | Week 36 - abnormal - right eye | 9 Participants |
| Vehicle | Microperimetry | Week 24 - normal - left eye | 1 Participants |
| Vehicle | Microperimetry | Week 12 - abnormal - right eye | 7 Participants |
| Vehicle | Microperimetry | Wk 48 - abnormal - left eyew | 9 Participants |
| Vehicle | Microperimetry | Wk 24 - abnormal - left eye | 8 Participants |
| Vehicle | Microperimetry | Wk 24 - normal - right eye | 1 Participants |
| Vehicle | Microperimetry | Week 12 - normal - right eye | 1 Participants |
| Vehicle | Microperimetry | Wk 48 - normal - left eye | 1 Participants |
| Vehicle | Microperimetry | Wk 24 - abnormal - right eye | 8 Participants |
| Vehicle | Microperimetry | Week 12 - abnormal - left eye | 7 Participants |
Secondary
Ocular Coherence Tomography (OCT)
Ocular coherence tomography was performed to evaluate the cross-sectional anatomy of the macula and to document areas of retinal atrophy.
Time frame: Day 0, Weeks 12, 24, 36 and 48
Population: Intent to treat (ITT) population: all randomized patients. The ITT population was used for the exploratory analyses of ocular parameters.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 48 - normal - left eye | 2 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 24 - abnormal - right eye | 14 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 12 - normal - right eye | 8 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Day 0 - abnormal - left eye | 14 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 24 - normal - right eye | 3 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 12 - abnormal - right eye | 12 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 48 - abnormal - right eye | 17 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 24 - abnormal - left eye | 15 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 24 - normal - left eye | 2 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 36 - abnormal - right eye | 13 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Day 0 - normal - right eye | 7 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 48 - abnormal - left eye | 17 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 36 - normal - right eye | 5 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Day 0 - abnormal - right eye | 13 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Day 0 - normal - left eye | 6 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 36 - abnormal - left eye | 14 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 12 - normal - left eye | 7 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 48 - normal - right eye | 2 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 36 - normal - left eye | 4 Participants |
| rhNGF 60µg/ml | Ocular Coherence Tomography (OCT) | Wk 12 - abnormal - left eye | 13 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 36 - normal - right eye | 3 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Day 0 - normal - left eye | 4 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Day 0 - abnormal - left eye | 16 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Day 0 - normal - right eye | 4 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Day 0 - abnormal - right eye | 16 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 12 - normal - left eye | 2 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 12 - abnormal - left eye | 18 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 12 - normal - right eye | 3 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 12 - abnormal - right eye | 17 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 24 - normal - left eye | 1 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 24 - normal - right eye | 2 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 24 - abnormal - right eye | 17 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 36 - normal - left eye | 3 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 36 - abnormal - left eye | 16 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 24 - abnormal - left eye | 18 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 36 - abnormal - right eye | 16 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 48 - normal - left eye | 3 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 48 - abnormal - left eye | 16 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 48 - normal - right eye | 3 Participants |
| rhNGF 180 µg/ml | Ocular Coherence Tomography (OCT) | Wk 48 - abnormal - right eye | 16 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 36 - normal - left eye | 0 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Day 0 - abnormal - right eye | 10 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 48 - normal - right eye | 0 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 36 - abnormal - left eye | 9 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Day 0 - normal - right eye | 0 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 48 - abnormal - left eye | 10 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 36 - normal - right eye | 0 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Day 0 - abnormal - left eye | 10 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 24 - abnormal - left eye | 8 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 36 - abnormal - right eye | 9 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 24 - normal - left eye | 2 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 12 - abnormal - right eye | 10 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 24 - abnormal - right eye | 8 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 12 - normal - right eye | 0 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Day 0 - normal - left eye | 0 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 24 - normal - right eye | 2 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 12 - abnormal - left eye | 10 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 48 - abnormal - right eye | 10 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 12 - normal - left eye | 0 Participants |
| Vehicle | Ocular Coherence Tomography (OCT) | Wk 48 - normal - left eye | 0 Participants |