A 8 Weeks Study to Evaluate Efficacy & Safety of rhNGF vs Vehicle in Patients After Cataract and Refractive Surgery

• Sponsor: Dompé Farmaceutici S.p.A (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03035864
• Collaborator: (none)
• Enrollment: 180
• Location: 1
• Arms: 2
• Actual Duration (Months): 7.7
• Patients Per Site Per Month: 23.3

Study Details

Study Description

Brief Summary

The primary objective of this exploratory study is to assess preliminary efficacy and safety of rhNGF when administered as eye drops to patients after cataract and refractive surgery.

The main criteria for evaluation were:

• Change from baseline in SANDE scores for severity and frequency assessed at 8 weeks of treatment (primary efficacy endpoint)

• Changes in Cornea vital staining with fluorescein (National Eye Institute [NEI] scales) assessed at 8 weeks of treatment (co-primary efficacy endpoint)

• Changes in conjunctiva vital staining with fluorescein (NEI scales) (secondary efficacy endpoint);

• Changes in Tear Film Break-Up Time (TFBUT)(secondary efficacy endpoint);

• Changes in Cochet-Bonnet corneal aesthesiometry (secondary efficacy endpoint);

• Changes in Nerve count and morphology at scanning laser in vivo corneal confocal microscopy (only patients who had Laser-Assisted In situ Keratomileusis [LASIK] surgery) (secondary efficacy endpoint);

• Changes in SANDE scores (face values) for severity and frequency (secondary efficacy endpoint);

• Incidence and frequency of treatment-emergent adverse events (TEAEs), assessed throughout the study (safety endpoint).

Condition or Disease	Intervention/Treatment	Phase
Ocular Discomfort	Drug: rhNGF; Other: Vehicle	Phase 2

Detailed Description

The proposed phase II study is a single-centre, randomized, double masked, parallel arm, vehicle-controlled trial, designed to evaluate the preliminary efficacy and safety of rhNGF eye drops at 20 µg/ml concentration administered six times daily for 8 weeks in patients who underwent cataract and corneal refractive surgery, both known to damage the corneal sensory nerve plexus.

After confirmation of inclusion and exclusion criteria all eligible patients will be randomized at 2:1 ratio to rhNGF or vehicle control treatment with 8 weeks of study treatments administration with 4 weeks Follow-up.

Study Design

• Study Type: Interventional
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: For the whole duration of the trial, treatment was unknown to the patient, the Investigator and the site staff.
• Primary Purpose: Treatment
• Official Title: A 8 Weeks, Phase II, Single-centre, Randomized, Double-masked, Vehicle-controlled, Parallel Group Study With 4 Weeks Follow-up to Evaluate Efficacy & Safety of rhNGF Eye Drops vs Vehicle in Patients After Cataract and Refractive Surgery
• Actual Study Start Date: Jan 12, 2017
• Actual Primary Completion Date: Sep 4, 2017
• Actual Study Completion Date: Sep 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rhNGF 20 µg/ml Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily	Drug: rhNGF; Eye Drop 20 μg/mL; Other Names: NGF
Placebo Comparator: Vehicle Vehicle eye drops six times daily	Other: Vehicle; Vehicle Eye Drop

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in SANDE Scores for Frequency and Severity Assessed at 8 Weeks of Treatment. [Baseline and Week 8]

   The Symptom Assessment in Dry Eye (SANDE) questionnaire is a short questionnaire to evaluate both dry eye intensity and frequency by using a 100 mm visual analogue scale (VAS). The patient symptoms of ocular dryness and/or irritation were quantified on the scale based on two questions that assessed both the severity and frequency of symptoms. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.

2. Changes in Cornea Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) [Baseline and Week 8]

   Corneal Staining was derived as the sum of scores of the five corneal sectors (central, superior, inferior, nasal, and temporal) each of which was scored on a scale of 0-3, with a minimum score of 0 and a maximal score of 15 (sum > 3 out of 15 is abnormal).

Secondary Outcome Measures

1. Changes in Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) [From baseline to weeks 4, 8 and 12]

   Conjunctival Staining was derived as the sum of scores of the conjunctival area (nasal-superior paralimbal, nasal-inferior paralimbal, nasal-peripheral, temporal-superior paralimbal, temporal-inferior paralimbal, temporal-peripheral) with a grading scale of 0-3 and with a minimum score of 0 and a maximal score of 18 (18 indicates the most abnormal score). Grades increase with the number and density of dots. Data for the main eye are reported.

2. Changes in Tear Film Break-Up Time (TFBUT) [From baseline to weeks 4, 8 and 12]

   The TFBUT measurement was performed after instillation of 5 microliters of 2% sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient was instructed to blink several times to thoroughly mix the fluorescein with the tear film. Data for the main eye are reported.

3. Changes in Cochet-Bonnet Corneal Aesthesiometry [From baseline to week 8]

   Corneal sensation was measured in both eyes in each of the four quadrants of the cornea using the Cochet Bonnet aesthesiometer before the instillation of any dilating or anesthetic eye drops. The handheld esthesiometer (Cochet-Bonnet) is a device that contains a thin, retractable, nylon monofilament that extends up to 6 cm in length. Variable pressure can be applied by the device by adjusting the length. The monofilament ranges from 60 mm to 5 mm and as the length is decreased the pressure increases from 11 mm/gm to 200 mm/gm. Data for the main eye are reported.

4. Changes in SANDE Scores (Face Values) for Frequency and Severity [From baseline to weeks 4, 8 and 12]

   The Symptom Assessment in Dry Eye (SANDE) questionnaire is a short questionnaire to evaluate both dry eye intensity and frequency by using a 100 mm visual analogue scale (VAS). The patient symptoms of ocular dryness and/or irritation were quantified on the scale based on two questions that assessed both the severity and frequency of symptoms. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female ≥18 years old

2. Patients who are characterized by the following clinical features:

3. History of cataract or refractive corneal surgery in the study eye(s) in the previous 6 months;

4. Mean Symptom Assessment in Dry Eye (SANDE) score for severity and frequency of at least 30 at baseline

5. The same eye (study eye) must fulfill all the above criteria

6. Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units in both eyes at the time of study enrolment

7. Female patients must have negative pregnancy urine test if at childbirth potential.

8. Only patients who satisfy all requirements for informed consent may be included in the study. Written Informed Consent must be obtained before the initiation of any study-specific procedures.

9. Patients must have the ability and willingness to comply with study procedures

Exclusion Criteria:

1. Any ocular disease other than Dry Eye requiring treatment with topical medications in either eye at the time of study enrolment.

2. Any active ocular infection or active inflammation in either eye unrelated to Dry Eye.

3. Presence or history of any systemic or ocular disorder, condition or disease (with particular attention to malignancies and neuro-oncological diseases) that could possibly interfere with the conduct of the required study procedures or the interpretation of the study results.

4. Use of therapeutic or Refractive Contact lenses in either eye at the time of study enrolment;

5. History of ocular surgery in the study eye(s), excluding corneal refractive or cataract procedures, within 90 days of study enrolment.

6. Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions:

7. are currently pregnant or,

8. have a positive result at the urine pregnancy test (Baseline/Day 0) or,

9. intend to become pregnant during the study treatment period or,

10. are breast-feeding or,

11. are not willing to use highly effective birth control measures, such as: hormonal contraceptives - oral, implanted, transdermal, or injected - and/or mechanical barrier methods - spermicide in conjunction with a barrier such as a condom or diaphragm or IUD (Intrauterine device) - during the entire course of and 30 days after the study treatment periods.

12. Participation in another clinical study at the same time as the present and within 30 days of study enrolment;

13. History of drug, medication or alcohol abuse or addiction.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ. G. D'Annunzio-Clinica Oftalmologica-Chieti	Chieti		Italy

Sponsors and Collaborators

• Dompé Farmaceutici S.p.A

Investigators

• Principal Investigator: Leonardo Mastropasqua, MD, Univ. G. D'Annunzio- Clinica Oftalmologica Chieti

Study Documents (Full-Text)

• Study Protocol - Apr 12, 2017
• Statistical Analysis Plan - Jul 11, 2017

More Information

Publications

None provided.

• Responsible Party: Dompé Farmaceutici S.p.A
• ClinicalTrials.gov Identifier: NCT03035864
• Other Study ID Numbers: NGF0116
• First Posted: Jan 30, 2017
• Last Update Posted: Jul 22, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Dompé Farmaceutici S.p.A: Ocular discomfort after cataract and refractive surgery; cataract surgery; refractive surgery
• Additional relevant MeSH terms: Cataract; Capsule Opacification

Study Results

Participant Flow

Recruitment Details	Eligible patients were randomized in a 2:1 ratio to rhNGF eye drops solution at 20 μg/ml (120 patients) or vehicle eye drops solution (60 patients) 6 times per day for 8 weeks, followed by 4 weeks of follow-up with no further treatment.

Arm/Group Title	rhNGF 20 µg/ml	Vehicle
Arm/Group Description	Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily rhNGF: Eye Drop 20 μg/mL	Vehicle eye drops six times daily Vehicle: Vehicle Eye Drop
Period Title: Treatment Period
STARTED	120	60
COMPLETED	116	59
NOT COMPLETED	4	1
Period Title: Treatment Period
STARTED	116	59
COMPLETED	105	55
NOT COMPLETED	11	4

Baseline Characteristics

Arm/Group Title	rhNGF 20 µg/ml	Vehicle	Total
Arm/Group Description	Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily rhNGF: Eye Drop 20 μg/mL	Vehicle eye drops six times daily Vehicle: Vehicle Eye Drop	Total of all reporting groups
Overall Participants	115	59	174
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.0 (12.80)	34.4 (11.20)	36.8 (12.36)
Sex: Female, Male (Count of Participants)
Female	71 61.7%	33 55.9%	104 59.8%
Male	44 38.3%	26 44.1%	70 40.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 3.4%	2 1.1%
Not Hispanic or Latino	115 100%	57 96.6%	172 98.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Italy	115 100%	59 100%	174 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in SANDE Scores for Frequency and Severity Assessed at 8 Weeks of Treatment.
Description	The Symptom Assessment in Dry Eye (SANDE) questionnaire is a short questionnaire to evaluate both dry eye intensity and frequency by using a 100 mm visual analogue scale (VAS). The patient symptoms of ocular dryness and/or irritation were quantified on the scale based on two questions that assessed both the severity and frequency of symptoms. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set Population. Last observation carried forward (LOCF) imputation method

Arm/Group Title	rhNGF 20 µg/ml	Vehicle
Arm/Group Description	Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily rhNGF: Eye Drop 20 μg/mL	Vehicle eye drops six times daily Vehicle: Vehicle Eye Drop
Measure Participants	112	58
Frequency	-37.2 (24.85)	-35.7 (26.04)
Severity	-37.8 (27.20)	-37.3 (20.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rhNGF 20 µg/ml, Vehicle
	Comments	Frequency statistical analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.974
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	difference in LS means
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -6.85 to 6.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	rhNGF 20 µg/ml, Vehicle
	Comments	Statistical analysis related to severity
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.399
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least square means
	Estimated Value	2.88
	Confidence Interval	(2-Sided) 95%; -3.85 to 9.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Changes in Cornea Vital Staining With Fluorescein (National Eye Institute [NEI] Scales)
Description	Corneal Staining was derived as the sum of scores of the five corneal sectors (central, superior, inferior, nasal, and temporal) each of which was scored on a scale of 0-3, with a minimum score of 0 and a maximal score of 15 (sum > 3 out of 15 is abnormal).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set population. Last observation carried forward (LOCF) imputation method.

Arm/Group Title	rhNGF 20 µg/ml	Vehicle
Arm/Group Description	Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily rhNGF: Eye Drop 20 μg/mL	Vehicle eye drops six times daily Vehicle: Vehicle Eye Drop
Measure Participants	112	58
Mean (Standard Deviation) [score on a scale]	-2.5 (2.11)	-2.2 (1.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rhNGF 20 µg/ml, Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.214
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	difference in least square means
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Changes in Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales)
Description	Conjunctival Staining was derived as the sum of scores of the conjunctival area (nasal-superior paralimbal, nasal-inferior paralimbal, nasal-peripheral, temporal-superior paralimbal, temporal-inferior paralimbal, temporal-peripheral) with a grading scale of 0-3 and with a minimum score of 0 and a maximal score of 18 (18 indicates the most abnormal score). Grades increase with the number and density of dots. Data for the main eye are reported.
Time Frame	From baseline to weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

As of this secondary endpoint, FAS Population was taken into account, but the last observation carried forward (LOCF) imputation method was not applied. Due to the reason mentioned above, the patients actually analysed (n) were the following: Week 4 - 110 rhNGF; 58 vehicle Week 8 - 107 rhNGF; 58 vehicle Week 12 - 107 rhNGF; 55 vehicle

Arm/Group Title	rhNGF 20 µg/ml	Vehicle
Arm/Group Description	Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily rhNGF: Eye Drop 20 μg/mL	Vehicle eye drops six times daily Vehicle: Vehicle Eye Drop
Measure Participants	112	58
week 4	0.0 (0.00)	0.0 (0.00)
week 8	0.0 (0.00)	0.0 (0.00)
week 12	0.0 (0.00)	0.0 (0.00)

4. Secondary Outcome

Title	Changes in Tear Film Break-Up Time (TFBUT)
Description	The TFBUT measurement was performed after instillation of 5 microliters of 2% sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient was instructed to blink several times to thoroughly mix the fluorescein with the tear film. Data for the main eye are reported.
Time Frame	From baseline to weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

As of this secondary endpoint, FAS Population was taken into account, but the last observation carried forward (LOCF) imputation method was not applied. Due to the reason mentioned above, the patients actually analysed (n) were the following: Week 4 - 110 rhNGF Week 8 - 107 rhNGF Week 12 - 107 rhNGF

Arm/Group Title	rhNGF 20 µg/ml	Vehicle
Arm/Group Description	Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily rhNGF: Eye Drop 20 μg/mL	Vehicle eye drops six times daily Vehicle: Vehicle Eye Drop
Measure Participants	112	58
week 4	2.5 (3.07)	2.5 (2.37)
week 8	1.9 (2.96)	2.2 (2.67)
week 12	2.3 (2.61)	2.7 (2.72)

5. Secondary Outcome

Title	Changes in Cochet-Bonnet Corneal Aesthesiometry
Description	Corneal sensation was measured in both eyes in each of the four quadrants of the cornea using the Cochet Bonnet aesthesiometer before the instillation of any dilating or anesthetic eye drops. The handheld esthesiometer (Cochet-Bonnet) is a device that contains a thin, retractable, nylon monofilament that extends up to 6 cm in length. Variable pressure can be applied by the device by adjusting the length. The monofilament ranges from 60 mm to 5 mm and as the length is decreased the pressure increases from 11 mm/gm to 200 mm/gm. Data for the main eye are reported.
Time Frame	From baseline to week 8

Outcome Measure Data

Analysis Population Description

As of this secondary endpoint, FAS Population was taken into account, but the last observation carried forward (LOCF) imputation method was not applied.

Arm/Group Title	rhNGF 20 µg/ml	Vehicle
Arm/Group Description	Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily rhNGF: Eye Drop 20 μg/mL	Vehicle eye drops six times daily Vehicle: Vehicle Eye Drop
Measure Participants	107	58
superior nasal	-0.1 (0.31)	-0.2 (0.31)
inferior nasal	-0.2 (0.32)	-0.1 (0.64)
superior temporal	-0.2 (0.36)	-0.2 (0.34)
inferior temporal	-0.1 (0.41)	0.0 (0.64)

6. Secondary Outcome

Title	Changes in SANDE Scores (Face Values) for Frequency and Severity
Description	The Symptom Assessment in Dry Eye (SANDE) questionnaire is a short questionnaire to evaluate both dry eye intensity and frequency by using a 100 mm visual analogue scale (VAS). The patient symptoms of ocular dryness and/or irritation were quantified on the scale based on two questions that assessed both the severity and frequency of symptoms. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.
Time Frame	From baseline to weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set Population. Observed values are reported.

Arm/Group Title	rhNGF 20 µg/ml	Vehicle
Arm/Group Description	Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily rhNGF: Eye Drop 20 μg/mL	Vehicle eye drops six times daily Vehicle: Vehicle Eye Drop
Measure Participants	112	58
Frequency - week 4	-35.1 (22.37)	-33.2 (25.18)
Frequency - week 8	-37.2 (24.84)	-35.7 (26.04)
Frequency - week 12	-42.1 (22.94)	-38.6 (26.25)
Severity - week 4	-35.7 (24.28)	-32.9 (20.03)
Severity - week 8	-37.9 (27.51)	-37.3 (20.43)
Severity - week 12	-43.5 (22.7)	-38.4 (20.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rhNGF 20 µg/ml, Vehicle
	Comments	Frequency - week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.881
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	difference in least square means
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -6.13 to 5.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	rhNGF 20 µg/ml, Vehicle
	Comments	Frequency - week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.926
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	difference in least square means
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -6.96 to 6.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	rhNGF 20 µg/ml, Vehicle
	Comments	Frequency - Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.426
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	difference in least square means
	Estimated Value	-2.29
	Confidence Interval	(2-Sided) 95%; -7.97 to 3.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	rhNGF 20 µg/ml, Vehicle
	Comments	Severity - Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.828
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in least square means
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; -5.04 to 6.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	rhNGF 20 µg/ml, Vehicle
	Comments	Severity - Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.394
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	difference in least square means
	Estimated Value	2.86
	Confidence Interval	(2-Sided) 95%; -3.75 to 9.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	rhNGF 20 µg/ml, Vehicle
	Comments	Severeity - Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.552
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	difference in least square means
	Estimated Value	-1.49
	Confidence Interval	(2-Sided) 95%; -6.41 to 3.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events were collected at each time point of the study (ie. Baseline visit, Week 4, Week 8 and week 12 (follow-up visit)
Adverse Event Reporting Description	Overall Summary of Adverse Events is calculated on the Analysed for safety (SAF) population, i.e. 115 patients in the rhNGF group and 59 in the vehicle group.
Arm/Group Title	rhNGF 20 µg/ml		Vehicle
Arm/Group Description	Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily rhNGF: Eye Drop 20 μg/mL		Vehicle eye drops six times daily Vehicle: Vehicle Eye Drop
All Cause Mortality
	rhNGF 20 µg/ml		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/115 (0%)		0/59 (0%)
Serious Adverse Events
	rhNGF 20 µg/ml		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/115 (0.9%)		0/59 (0%)
Infections and infestations
Appendicitis	1/115 (0.9%)	1	0/59 (0%)	0
Other (Not Including Serious) Adverse Events
	rhNGF 20 µg/ml		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/115 (43.5%)		19/59 (32.2%)
Eye disorders
Eye pain	23/115 (20%)	33	2/59 (3.4%)	2
Eye irritation	13/115 (11.3%)	21	10/59 (16.9%)	12
Vision blurred	7/115 (6.1%)	7	10/59 (16.9%)	12
Myopia	10/115 (8.7%)	10	4/59 (6.8%)	4
Dry eye	6/115 (5.2%)	8	6/59 (10.2%)	11
Eye swelling	4/115 (3.5%)	5	2/59 (3.4%)	2
photophobia	3/115 (2.6%)	4	3/59 (5.1%)	3
Eyelid oedema	3/115 (2.6%)	3	0/59 (0%)	0
foreign body sensation in eyes	2/115 (1.7%)	2	1/59 (1.7%)	1
Visual impairment	1/115 (0.9%)	1	1/59 (1.7%)	2
Diplopia	1/115 (0.9%)	1	1/59 (1.7%)	1
Eye pruritus	1/115 (0.9%)	1	1/59 (1.7%)	1
Ocular hyperaemia	2/115 (1.7%)	2	0/59 (0%)	0
Blepharospasm	0/115 (0%)	0	1/59 (1.7%)	2
Conjunctival irritation	1/115 (0.9%)	1	0/59 (0%)	0
Corneal epithelium defect	1/115 (0.9%)	1	0/59 (0%)	0
Ocular discomfort	1/115 (0.9%)	1	0/59 (0%)	0
Photopsia	1/115 (0.9%)	1	0/59 (0%)	0
Gastrointestinal disorders
Nausea	2/115 (1.7%)	2	0/59 (0%)	0
Toothache	2/115 (1.7%)	2	0/59 (0%)	0
Dyspepsia	1/115 (0.9%)	1	0/59 (0%)	0
Gastrointestinal disorder	1/115 (0.9%)	1	0/59 (0%)	0
Mouth ulceration	1/115 (0.9%)	1	0/59 (0%)	0
General disorders
Fatigue	1/115 (0.9%)	1	0/59 (0%)	0
Swelling	1/115 (0.9%)	1	0/59 (0%)	0
Immune system disorders
Drug hypersensitivity	0/115 (0%)	0	1/59 (1.7%)	1
Infections and infestations
Rhinitis	2/115 (1.7%)	3	0/59 (0%)	0
Influenza	2/115 (1.7%)	2	0/59 (0%)	0
Appendicitis	1/115 (0.9%)	1	0/59 (0%)	0
Ear infection	1/115 (0.9%)	1	0/59 (0%)	0
Sinusitis	1/115 (0.9%)	1	0/59 (0%)	0
Injury, poisoning and procedural complications
Eye burns	1/115 (0.9%)	2	0/59 (0%)	0
Corneal abrasion	1/115 (0.9%)	1	0/59 (0%)	0
Nervous system disorders
Headache	9/115 (7.8%)	14	0/59 (0%)	0
Burning sensation	1/115 (0.9%)	1	0/59 (0%)	0
Dizziness	1/115 (0.9%)	1	0/59 (0%)	0
Psychiatric disorders
Anxiety	1/115 (0.9%)	1	0/59 (0%)	0
Respiratory, thoracic and mediastinal disorders
Rhinalgia	1/115 (0.9%)	3	0/59 (0%)	0
Nasal dryness	1/115 (0.9%)	1	0/59 (0%)	0
Rhinitis allergic	1/115 (0.9%)	1	0/59 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	1/115 (0.9%)	1	0/59 (0%)	0

Limitations/Caveats

LImitations and caveats non specified

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.