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An 8-week Study to Evaluate Safety and Efficacy of NGF Eye Drops Solution Versus Vehicle in Patients With Dry Eye

Primary Purpose

Dry Eye

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

NGF

Vehicle

About this trial

This is an interventional treatment trial for Dry Eye

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients (male or female) must be ≥ 18 years of age.
Patients must be diagnosed with any type of dry eye (e.g. Meibomian Gland Dysfunction, Blepharitis, Keratoconjunctivitis sicca etc) at least 3 months before enrollment.
Patients must present dry eye pathology characterized by the following clinical features:
1. Corneal and/or conjunctival staining with fluorescein and lissamine green using National Eye Institute (NEI) grading system > 3
2. Mean Symptom Assessment in Dry Eye (SANDE) questionnaire ≥30
3. Schirmer test without anesthesia < 10 mm/5 minutes and/or tear film break-up time (TFBUT) < 10 seconds in the study eye
The same eye (study eye) must fulfill all the above criteria.
Patients must have best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units in both eyes at the time of study enrollment.
Female patients must have negative pregnancy test if at childbirth potential.
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.
Patients must have the ability and willingness to comply with study procedures.

Exclusion Criteria:

Best corrected distance visual acuity (BCDVA) score of < 0.1 decimal units in either eye.
Evidence of an active ocular infection in either eye.
Presence or history of any ocular disorder or condition, including ocular surgery, trauma, or disease that could possibly interfere with the interpretation of study results in the opinion of the Investigator.
Intraocular inflammation defined as Tyndall score >0.
Active or recent diagnosis of malignancy (i.e., currently under chemo/radiotherapy).
Systemic disease not stabilized within 1 month before baseline visit (e.g., uncontrolled diabetes; thyroid malfunction) or judged by the Investigator to be incompatible with the study (e.g., current systemic infections) or with a condition incompatible with the frequent assessment required by the study.
Patients who have had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds, or had a clinically significant allergy to drugs, foods, amide local anesthetics, or other materials, including commercial artificial tears containing carboxymethylcellulose (CMC) (in the opinion of the Investigator).
Use of topical cyclosporine, topical corticosteroids, or any other topical medication for the treatment of dry eye in either eye until the day of study enrollment.
Contact lenses or punctal plug use during the study (previous use not an exclusion criteria, but must be discontinued at the baseline visit.
An anticipated need of additional systemic treatments for dry eye during the study (all prior treatment must be continued for the entire duration of the study).
Females of childbearing potential (those who are not surgically sterilized or postmenopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions:
1. are currently pregnant or,
2. have a positive result at the urine pregnancy test (Baseline/Day 0) or,
3. intend to become pregnant during the study treatment period or,
4. are breast-feeding or,
5. 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 a intrauterine device (IUD) - during the entire course of and 30 days after the study treatment periods.
History of drug addiction or alcohol abuse.
Any prior ocular surgery (including refractive palpebral and cataract surgery) if within 90 days before the screening visit.
Participation in a clinical trial with a new active substance during the past 30 days.
Participation in another clinical trial study at the same time as the present study.

Sites / Locations

Penn Dry Eye and Ocular Surface Center, University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

rhNGF 20μg/mL

Vehicle

Arm Description

Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily

vehicle eye drops six times daily

Outcomes

Primary Outcome Measures

Symptom Assessment in Dry Eye (SANDE) Scores

Change from baseline with Last Observation Carried Forward (LOCF) imputation. LOCF is a method of imputing missing data in longitudinal studies and tests for difference in mean rates of change in controlled repeated measurements designs with dropouts. 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.

Secondary Outcome Measures

SANDE Scores

Cornea Vital Staining

Changes from baseline on National Eye Institute (NEI) scale. The NEI/Industry Workshop guidelines were used for grading the scale of corneal and conjunctival damage. The cornea was divided into five sectors (central, superior, inferior, nasal and temporal), each of which was scored on a scale of 0-3, with a maximal total corneal staining score of 15. Both nasally and temporally, the conjunctiva was divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (overall the total score ranged from 0-18). Briefly, grade 0 reflected normal/healthy situation, whereas grade 3 reflected a severe damage in the considered sector.

Conjunctival Vital Staining

Change in Tear Film Break-up Time (TFBUT)

TFBUT was measured by determining the time to tear break-up. The TFBUT was performed after instillation of 5 μL of 2% preservative-free 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.

Change From Baseline in Wetting Distance

The Schirmer test without anesthesia was performed to measure aqueous tear secretion prior to the instillation of any dilating or eye drops

Full Information

NCT ID

NCT03019627

First Posted

January 11, 2017

Last Updated

January 16, 2019

Sponsor

Dompé Farmaceutici S.p.A

1. Study Identification

Unique Protocol Identification Number

NCT03019627

Brief Title

An 8-week Study to Evaluate Safety and Efficacy of NGF Eye Drops Solution Versus Vehicle in Patients With Dry Eye

Official Title

An 8-week, Phase II, Single-center, Randomized, Double-masked, Vehicle-controlled, Parallel-group Study With 4 Weeks of Follow-up to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution vs Vehicle in Patients With Dry Eye

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

January 20, 2017 (Actual)

Primary Completion Date

August 31, 2017 (Actual)

Study Completion Date

August 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Dompé Farmaceutici S.p.A

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The primary objective of this study was to assess the efficacy and safety of rhNGF when administered as eye drops to patients with dry eye The secondary objectives of this study were: To assess change from baseline in Symptom Assessment In Dry Eye (SANDE) scores (without imputation), corneal and conjunctival staining according to National Eye Institute (NEI) scale, and in Tear Film Break-up Time (TFBUT) and Schirmer test I, following 4 and 8 weeks of treatment. To assess change in levels of inflammatory biomarker matrix metallopeptidase 9 (MMP-9) in tears following 8 weeks of treatment. To assess the incidence and frequency of treatment-emergent adverse events (TEAEs) following 8 weeks of treatment.

Detailed Description

The proposed phase II study is a single-center, randomized, double-masked, parallel-arm, vehicle-controlled trial, designed to evaluate the safety and efficacy of Recombinant Human Nerve Growth Factor (rhNGF) eye drops at 20 μg/ml concentration administered six times daily for 8 weeks in patients with dry eye. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dry Eye

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Masking Description

The identity of the treatments was concealed from the patient, Investigator, site staff, and Dompé's clinical research personnel until the study was unmasked for the final statistical analysis (after data base lock) except in case of specific events that required unmasking of the patient.

Allocation

Randomized

Enrollment

150 (Actual)

8. Arms, Groups, and Interventions

Arm Title

rhNGF 20μg/mL

Arm Type

Experimental

Arm Description

Recombinant Human Nerve Growth Factor (rhNGF) at 20 μg/mL eye drops six times daily

Arm Title

Vehicle

Arm Type

Placebo Comparator

Arm Description

vehicle eye drops six times daily

Intervention Type

Drug

Intervention Name(s)

NGF

Other Intervention Name(s)

cenegermin

Intervention Description

Eye Drop 20 μg/mL

Intervention Type

Other

Intervention Name(s)

Vehicle

Other Intervention Name(s)

Placebo

Intervention Description

Vehicle Eye Drop

Primary Outcome Measure Information:

Title

Symptom Assessment in Dry Eye (SANDE) Scores

Description

Time Frame

week 8

Secondary Outcome Measure Information:

Title

SANDE Scores

Description

Time Frame

Week 4, week 8, week 12

Title

Cornea Vital Staining

Description

Time Frame

week 4, week 8, week 12

Title

Conjunctival Vital Staining

Description

Time Frame

week 4, week 8, week 12

Title

Change in Tear Film Break-up Time (TFBUT)

Description

Time Frame

week 4, week 8, week 12

Title

Change From Baseline in Wetting Distance

Description

The Schirmer test without anesthesia was performed to measure aqueous tear secretion prior to the instillation of any dilating or eye drops

Time Frame

week 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients (male or female) must be ≥ 18 years of age. Patients must be diagnosed with any type of dry eye (e.g. Meibomian Gland Dysfunction, Blepharitis, Keratoconjunctivitis sicca etc) at least 3 months before enrollment. Patients must present dry eye pathology characterized by the following clinical features: Corneal and/or conjunctival staining with fluorescein and lissamine green using National Eye Institute (NEI) grading system > 3 Mean Symptom Assessment in Dry Eye (SANDE) questionnaire ≥30 Schirmer test without anesthesia < 10 mm/5 minutes and/or tear film break-up time (TFBUT) < 10 seconds in the study eye The same eye (study eye) must fulfill all the above criteria. Patients must have best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units in both eyes at the time of study enrollment. Female patients must have negative pregnancy test if at childbirth potential. 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. Patients must have the ability and willingness to comply with study procedures. Exclusion Criteria: Best corrected distance visual acuity (BCDVA) score of < 0.1 decimal units in either eye. Evidence of an active ocular infection in either eye. Presence or history of any ocular disorder or condition, including ocular surgery, trauma, or disease that could possibly interfere with the interpretation of study results in the opinion of the Investigator. Intraocular inflammation defined as Tyndall score >0. Active or recent diagnosis of malignancy (i.e., currently under chemo/radiotherapy). Systemic disease not stabilized within 1 month before baseline visit (e.g., uncontrolled diabetes; thyroid malfunction) or judged by the Investigator to be incompatible with the study (e.g., current systemic infections) or with a condition incompatible with the frequent assessment required by the study. Patients who have had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds, or had a clinically significant allergy to drugs, foods, amide local anesthetics, or other materials, including commercial artificial tears containing carboxymethylcellulose (CMC) (in the opinion of the Investigator). Use of topical cyclosporine, topical corticosteroids, or any other topical medication for the treatment of dry eye in either eye until the day of study enrollment. Contact lenses or punctal plug use during the study (previous use not an exclusion criteria, but must be discontinued at the baseline visit. An anticipated need of additional systemic treatments for dry eye during the study (all prior treatment must be continued for the entire duration of the study). Females of childbearing potential (those who are not surgically sterilized or postmenopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions: are currently pregnant or, have a positive result at the urine pregnancy test (Baseline/Day 0) or, intend to become pregnant during the study treatment period or, are breast-feeding or, 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 a intrauterine device (IUD) - during the entire course of and 30 days after the study treatment periods. History of drug addiction or alcohol abuse. Any prior ocular surgery (including refractive palpebral and cataract surgery) if within 90 days before the screening visit. Participation in a clinical trial with a new active substance during the past 30 days. Participation in another clinical trial study at the same time as the present study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Giacomina Massaro Giordano, MD

Organizational Affiliation

Penn Dry Eye and Oc. Surf. Center, Univ. of Pennsylvania, Scheie Eye Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Penn Dry Eye and Ocular Surface Center, University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

An 8-week Study to Evaluate Safety and Efficacy of NGF Eye Drops Solution Versus Vehicle in Patients With Dry Eye

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