Back to resultsA Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye
Primary Purpose
Dry Eye Syndrome
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rhNGF 20 μg/ml
rhNGF 20 μg/ml + vehicle
Vehicle
Sponsored by
About this trial
This is an interventional treatment trial for Dry Eye Syndrome
Eligibility Criteria
Inclusion Criteria:
- Male or female aged ≥ 18 years
Patients with moderate to severe dry eye characterized by the following clinical features:
- Corneal and/or conjunctival staining with fluorescein using National Eye Institute (NEI) grading system > 3
- SANDE questionnaire >25 mm
- Schirmer test I (without anaesthesia) >2mm <10 mm/5 minutes
- Tear film break-up time (TFBUT) < 10 seconds in the worse eye
- The same eye (eligible eye) must fulfill all the above criteria
- Patients diagnosed with dry eye at least 6 months before enrolment (current use or recommended use of artificial tears for the treatment of Dry Eye)
- Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200 Snellen value) in both eyes at the time of study enrolment
- If a female of childbearing potential, have a negative pregnancy test
- Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative 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 legal representative must have been approved by the Institutional Review Board (IRB) / Independent Ethics Committee (IEC) for the current study
- Patients must have the ability and willingness to comply with study procedures.
Exclusion Criteria:
- Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments;
- Evidence of an active ocular infection, in either eye
- Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study
- History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye
- Intraocular inflammation defined as Tyndall score >0
- History of malignancy in the last 5 years
- Systemic disease not stabilized within 1 month before Screening Visit (e.g. diabetes with glycemia out of range, 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
- Patient 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 anaesthetics or other materials including commercial artificial tears (in the opinion of the investigator)
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:
- 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 Intra Uterine Device (IUD) - during the entire course of and 30 days after the study treatment periods
- Any concurrent medical condition, that in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient's well-being
- Use of topical cyclosporine, topical corticosteroids or any other topical drug for the treatment of dry eye in either eye within 30 days of study enrolment.
- Contact lenses or punctum plug use during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)
- 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 6 months
- Participation in another clinical trial study at the same time as the present study.
Sites / Locations
- Global Research Management
- Eye Research Foundation
- Martel Eye Medical Group
- Sierra Clinical Trials & Research Organization
- Clayton Eye Clinical Research, LLC
- Kentucky Eye Institute
- Tauber Eye Center
- Moyes Eye Center
- SightMD
- Toyos Clinic
- Houston Eye Associates HEA - Gramercy Location
- Advanced Laser Vision Surgical Institute (Study Site) Intouch Clinical Research Center (SMO)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
rhNGF 20 μg/ml TID
rhNGF 20 μg/ml BID + vehicle OD
Vehicle TID
Arm Description
One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)
One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours)
Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours)
Outcomes
Primary Outcome Measures
Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set
The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye.
Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes.
The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes)
Cutoff values:
<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Per Protocol Set
The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye.
Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes.
The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes)
Cutoff values:
<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
Secondary Outcome Measures
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Full Analysis Set
The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The global score is calculated by taking the square root of the product of the severity of symptoms per the frequency of symptoms. 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.
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Per Protocol Set
The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The global score is calculated by taking the square root of the product of the severity of symptoms per the frequency of symptoms. 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.
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Full Analysis Set
The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome.The SANDE global score is calculated by taking the square root of the product of the frequency of symptoms and the severity of symptoms. The SANDE scale ranges from 0 to 100 wi.100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Per Protocol Set
The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score. The SANDE scale ranges from 0 to 100 wi.100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.
Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Full Analysis Set
The Schirmer II test is performed as the Schirmer I test after instilling anesthetic drops. The Schirmer strips are inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. All patients are seated at rest with their eyes closed, and the lower cul-de-sac is gently dried with a cotton applicator before the placement of strips.
Cut-off values:
<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Per Protocol Set
The Schirmer II test is performed as the Schirmer I test after instilling anesthetic drops. The Schirmer strips are inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes.
All patients are seated at rest with their eyes closed, and the lower cul-de-sac is gently dried with a cotton applicator before the placement of strips.
Cut-off values:
<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set
Corneal staining total score is defined as the sum of scores from 5 corneal areas: Central, Superior, Temporal, Nasal, and Inferior. The score for each area ranges from 0 to 3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage. Thus, the corneal staining total score can range from 0 to 15 where the higher the score the worse is the outcome.
The conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage and with a maximal score of 9 for the nasal and temporal conjunctiva. Thus, the conjunctival staining total score can range from 0 to 18 where the higher the score the worse is the outcome.
Corneal and conjunctiva vital staining total score is the sum of corneal staining total score and conjunctiva total score.
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set
Corneal staining total score is defined as the sum of scores from 5 corneal areas: Central, Superior, Temporal, Nasal, and Inferior. The score for each area ranges from 0 to 3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage. Thus, the corneal staining total score can range from 0 to 15 where the higher the score the worse is the outcome.
The conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage and with a maximal score of 9 for the nasal and temporal conjunctiva. Thus, the conjunctival staining total score can range from 0 to 18 where the higher the score the worse is the outcome.
Corneal and conjunctiva vital staining total score is the sum of corneal staining total score and conjunctiva total score.
Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Full Analysis Set
Tear film break-up time (TFBUT) is the time taken to appear first dry spot on cornea after a complete blinking. TFBUT measurement is an easy and fast method used to assess the stability of tear film. It is a standard diagnostic procedure in the dry eye clinics. TFBUT is measured by determining the time to tear break-up. The TFBUT is 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 is instructed to blink several times to thoroughly mix the fluorescein with the tear film.
A TFBUT greater than 15 seconds is considered normal, while a break time of less than 10 seconds is to be considered pathological.
Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Per Protocol Set
Tear film break-up time (TFBUT) is the time taken to appear first dry spot on cornea after a complete blinking. TFBUT measurement is an easy and fast method used to assess the stability of tear film. It is a standard diagnostic procedure in the dry eye clinics. TFBUT is measured by determining the time to tear break-up. The TFBUT is 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 is instructed to blink several times to thoroughly mix the fluorescein with the tear film.
A TFBUT greater than 15 seconds is considered normal, while a break time of less than 10 seconds is to be considered pathological.
Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Full Analysis Set
The SANDE score is calculated by taking the square root of the product of 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.
The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage.
The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15.
Both nasally and temporally, the conjunctiva is 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 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector.
Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Per Protocol Set
The SANDE score is calculated by taking the square root of the product of 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.
The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage.
The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15.
Both nasally and temporally, the conjunctiva is 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 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector.
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set
IDEEL assesses quality of life, symptoms and treatment effects on patients with dry eye.
The IDEEL contains 3 modules (Daily Activities, Treatment Satisfaction, and Symptom Bother) with a total of 57 questions.
The Daily Activities Module is the quality of life instrument. It is comprised of 27 items.
The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops.
The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother.
Scores for each dimensions ranged from 0 to 100.
Higher scores for:
dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities;
symptom-bother dimension indicates greater bother due to symptoms;
satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness;
treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience.
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set
IDEEL assesses quality of life, symptoms and treatment effects on patients with dry eye.
The IDEEL contains 3 modules (Daily Activities, Treatment Satisfaction, and Symptom Bother) with a total of 57 questions.
The Daily Activities Module is the quality of life instrument. It is comprised of 27 items.
The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops.
The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother.
Scores for each dimensions ranged from 0 to 100.
Higher scores for:
dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities;
symptom-bother dimension indicates greater bother due to symptoms;
satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness;
treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience.
Patient Global Impression of Change (PGIC) - Full Analysis Set
PGIC is a commonly used method of assessing clinically important change. With PGIC the qualitative assessment of meaningful change is determined by the patient on 7-items using a 0 (very much improved) to 10 (very much worse) scale.
Patient Global Impression of Change (PGIC) - Per Protocol Set
PGIC is a commonly used method of assessing clinically important change. With PGIC the qualitative assessment of meaningful change is determined by the patient on 7-items using a 0 (very much improved) to 10 (very much worse) scale.
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set
EQ-5D is a standardised measure of health status. - The EQ-5D 3 level version (EQ-5D-3L) consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) which are summed up.
The EQ-5D-3L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. This scale ranges from 5 (best case) to 15 (worst case).
Each dimension has 3 levels: no problems, some problems, extreme problems (labelled 1-3). The respondent must indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
- The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This is a quantitative measure of health outcome, judged by each respondent.
Both for total and partial scores, the higher the score, the worse is the outcome.
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set
EQ-5D is a standardised measure of health status. - The EQ-5D 3 level version (EQ-5D-3L) consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) which are summed up.
The EQ-5D-3L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. This scale ranges from 5 (best case) to 15 (worst case).
Each dimension has 3 levels: no problems, some problems, extreme problems (labelled 1-3). The respondent must indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
- The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This is a quantitative measure of health outcome, judged by each respondent.
Both for total and partial scores, the higher the score, the worse is the outcome.
Full Information
NCT ID
NCT03982368
First Posted
May 23, 2019
Last Updated
December 5, 2022
Sponsor
Dompé Farmaceutici S.p.A
1. Study Identification
Unique Protocol Identification Number
NCT03982368
Brief Title
A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye
Official Title
A 4 Weeks, Phase II, Multicenter, Randomized, Double-masked, Vehicle-controlled, Parallel Group Study With 12 Weeks of Follow-up to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution vs Vehicle in Moderate to Severe Dry Eye.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
June 10, 2019 (Actual)
Primary Completion Date
July 15, 2020 (Actual)
Study Completion Date
July 15, 2020 (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
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this study is to assess the efficacy and safety of rhNGF eye drops at 20 μg/ml concentration administered two or three times daily for 4 weeks in patients with moderate to severe dry eye.
Detailed Description
This is a 4 weeks, Phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel group study with 12 weeks of follow-up, designed to perform dose-ranging and to evaluate safety and efficacy of recombinant human Nerve Growth Factor (rhNGF) eye drops solution versus vehicle, in patients with moderate to severe dry eye (DE).
Test product is rhNGF 20 μg/ml; reference product is vehicle. Test and reference will be instilled in both eyes according to the following scheme:
Group 1: one drop of rhNGF 20 μg/ml is instilled in both eyes three times daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).
Group 2: one drop of rhNGF 20 μg/ml is instilled in both eyes two times daily (in the morning and in the evening) plus one drop (40 μL) of vehicle (placebo) is instilled in both eyes once daily in the afternoon.
Group 3: one drop (40 μL) of vehicle (placebo) is instilled in both eyes three times daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).
Approximate randomization 1:1:1 of 261 patients to rhNGF eye drops solution 20 μg/ml TID (87 patients) or rhNGF eye drops solution 20 μg/ml BID + vehicle eye drop SID (86 patients) or vehicle eye drops solution (88 patients) TID for 4 weeks was applied.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Parallel groups
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double masked
Allocation
Randomized
Enrollment
261 (Actual)
8. Arms, Groups, and Interventions
Arm Title
rhNGF 20 μg/ml TID
Arm Type
Experimental
Arm Description
One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)
Arm Title
rhNGF 20 μg/ml BID + vehicle OD
Arm Type
Experimental
Arm Description
One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours)
Arm Title
Vehicle TID
Arm Type
Placebo Comparator
Arm Description
Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours)
Intervention Type
Drug
Intervention Name(s)
rhNGF 20 μg/ml
Other Intervention Name(s)
cenegermin
Intervention Description
one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)
Intervention Type
Drug
Intervention Name(s)
rhNGF 20 μg/ml + vehicle
Other Intervention Name(s)
cenegermin + placebo
Intervention Description
one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours).
rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.
Intervention Type
Other
Intervention Name(s)
Vehicle
Other Intervention Name(s)
placebo
Intervention Description
one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Primary Outcome Measure Information:
Title
Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set
Description
The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye.
Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes.
The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes)
Cutoff values:
<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
Time Frame
Baseline, week 4
Title
Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Per Protocol Set
Description
The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye.
Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes.
The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes)
Cutoff values:
<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
Time Frame
Baseline, week 4
Secondary Outcome Measure Information:
Title
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Full Analysis Set
Description
The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The global score is calculated by taking the square root of the product of the severity of symptoms per the frequency of symptoms. 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, week 4
Title
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Per Protocol Set
Description
The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The global score is calculated by taking the square root of the product of the severity of symptoms per the frequency of symptoms. 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, week 4
Title
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Full Analysis Set
Description
The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome.The SANDE global score is calculated by taking the square root of the product of the frequency of symptoms and the severity of symptoms. The SANDE scale ranges from 0 to 100 wi.100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms
Time Frame
Baseline, week 4
Title
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Per Protocol Set
Description
The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score. The SANDE scale ranges from 0 to 100 wi.100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.
Time Frame
Baseline, week 4
Title
Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Full Analysis Set
Description
The Schirmer II test is performed as the Schirmer I test after instilling anesthetic drops. The Schirmer strips are inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. All patients are seated at rest with their eyes closed, and the lower cul-de-sac is gently dried with a cotton applicator before the placement of strips.
Cut-off values:
<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
Time Frame
Baseline, week 4
Title
Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Per Protocol Set
Description
The Schirmer II test is performed as the Schirmer I test after instilling anesthetic drops. The Schirmer strips are inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes.
All patients are seated at rest with their eyes closed, and the lower cul-de-sac is gently dried with a cotton applicator before the placement of strips.
Cut-off values:
<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
Time Frame
Baseline, week 4
Title
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set
Description
Corneal staining total score is defined as the sum of scores from 5 corneal areas: Central, Superior, Temporal, Nasal, and Inferior. The score for each area ranges from 0 to 3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage. Thus, the corneal staining total score can range from 0 to 15 where the higher the score the worse is the outcome.
The conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage and with a maximal score of 9 for the nasal and temporal conjunctiva. Thus, the conjunctival staining total score can range from 0 to 18 where the higher the score the worse is the outcome.
Corneal and conjunctiva vital staining total score is the sum of corneal staining total score and conjunctiva total score.
Time Frame
Baseline, week 4
Title
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set
Description
Corneal staining total score is defined as the sum of scores from 5 corneal areas: Central, Superior, Temporal, Nasal, and Inferior. The score for each area ranges from 0 to 3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage. Thus, the corneal staining total score can range from 0 to 15 where the higher the score the worse is the outcome.
The conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage and with a maximal score of 9 for the nasal and temporal conjunctiva. Thus, the conjunctival staining total score can range from 0 to 18 where the higher the score the worse is the outcome.
Corneal and conjunctiva vital staining total score is the sum of corneal staining total score and conjunctiva total score.
Time Frame
Baseline, week 4
Title
Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Full Analysis Set
Description
Tear film break-up time (TFBUT) is the time taken to appear first dry spot on cornea after a complete blinking. TFBUT measurement is an easy and fast method used to assess the stability of tear film. It is a standard diagnostic procedure in the dry eye clinics. TFBUT is measured by determining the time to tear break-up. The TFBUT is 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 is instructed to blink several times to thoroughly mix the fluorescein with the tear film.
A TFBUT greater than 15 seconds is considered normal, while a break time of less than 10 seconds is to be considered pathological.
Time Frame
Baseline, week 4
Title
Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Per Protocol Set
Description
Tear film break-up time (TFBUT) is the time taken to appear first dry spot on cornea after a complete blinking. TFBUT measurement is an easy and fast method used to assess the stability of tear film. It is a standard diagnostic procedure in the dry eye clinics. TFBUT is measured by determining the time to tear break-up. The TFBUT is 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 is instructed to blink several times to thoroughly mix the fluorescein with the tear film.
A TFBUT greater than 15 seconds is considered normal, while a break time of less than 10 seconds is to be considered pathological.
Time Frame
Baseline, week 4
Title
Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Full Analysis Set
Description
The SANDE score is calculated by taking the square root of the product of 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.
The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage.
The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15.
Both nasally and temporally, the conjunctiva is 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 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector.
Time Frame
At week 4
Title
Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Per Protocol Set
Description
The SANDE score is calculated by taking the square root of the product of 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.
The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage.
The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15.
Both nasally and temporally, the conjunctiva is 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 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector.
Time Frame
At week 4
Title
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set
Description
IDEEL assesses quality of life, symptoms and treatment effects on patients with dry eye.
The IDEEL contains 3 modules (Daily Activities, Treatment Satisfaction, and Symptom Bother) with a total of 57 questions.
The Daily Activities Module is the quality of life instrument. It is comprised of 27 items.
The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops.
The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother.
Scores for each dimensions ranged from 0 to 100.
Higher scores for:
dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities;
symptom-bother dimension indicates greater bother due to symptoms;
satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness;
treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience.
Time Frame
At weeks 4, 8, 12 and 16
Title
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set
Description
IDEEL assesses quality of life, symptoms and treatment effects on patients with dry eye.
The IDEEL contains 3 modules (Daily Activities, Treatment Satisfaction, and Symptom Bother) with a total of 57 questions.
The Daily Activities Module is the quality of life instrument. It is comprised of 27 items.
The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops.
The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother.
Scores for each dimensions ranged from 0 to 100.
Higher scores for:
dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities;
symptom-bother dimension indicates greater bother due to symptoms;
satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness;
treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience.
Time Frame
At weeks 4, 8, 12 and 16
Title
Patient Global Impression of Change (PGIC) - Full Analysis Set
Description
PGIC is a commonly used method of assessing clinically important change. With PGIC the qualitative assessment of meaningful change is determined by the patient on 7-items using a 0 (very much improved) to 10 (very much worse) scale.
Time Frame
At baseline and weeks 4, 8, 12 and 16
Title
Patient Global Impression of Change (PGIC) - Per Protocol Set
Description
PGIC is a commonly used method of assessing clinically important change. With PGIC the qualitative assessment of meaningful change is determined by the patient on 7-items using a 0 (very much improved) to 10 (very much worse) scale.
Time Frame
At weeks 4, 8, 12 and 16
Title
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set
Description
EQ-5D is a standardised measure of health status. - The EQ-5D 3 level version (EQ-5D-3L) consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) which are summed up.
The EQ-5D-3L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. This scale ranges from 5 (best case) to 15 (worst case).
Each dimension has 3 levels: no problems, some problems, extreme problems (labelled 1-3). The respondent must indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
- The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This is a quantitative measure of health outcome, judged by each respondent.
Both for total and partial scores, the higher the score, the worse is the outcome.
Time Frame
At weeks 4, 8, 12 and 16
Title
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set
Description
EQ-5D is a standardised measure of health status. - The EQ-5D 3 level version (EQ-5D-3L) consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) which are summed up.
The EQ-5D-3L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. This scale ranges from 5 (best case) to 15 (worst case).
Each dimension has 3 levels: no problems, some problems, extreme problems (labelled 1-3). The respondent must indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
- The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This is a quantitative measure of health outcome, judged by each respondent.
Both for total and partial scores, the higher the score, the worse is the outcome.
Time Frame
Aat baseline and weeks 4, 8, 12 and 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female aged ≥ 18 years
Patients with moderate to severe dry eye characterized by the following clinical features:
Corneal and/or conjunctival staining with fluorescein using National Eye Institute (NEI) grading system > 3
SANDE questionnaire >25 mm
Schirmer test I (without anaesthesia) >2mm <10 mm/5 minutes
Tear film break-up time (TFBUT) < 10 seconds in the worse eye
The same eye (eligible eye) must fulfill all the above criteria
Patients diagnosed with dry eye at least 6 months before enrolment (current use or recommended use of artificial tears for the treatment of Dry Eye)
Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200 Snellen value) in both eyes at the time of study enrolment
If a female of childbearing potential, have a negative pregnancy test
Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative 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 legal representative must have been approved by the Institutional Review Board (IRB) / Independent Ethics Committee (IEC) for the current study
Patients must have the ability and willingness to comply with study procedures.
Exclusion Criteria:
Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments;
Evidence of an active ocular infection, in either eye
Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study
History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye
Intraocular inflammation defined as Tyndall score >0
History of malignancy in the last 5 years
Systemic disease not stabilized within 1 month before Screening Visit (e.g. diabetes with glycemia out of range, 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
Patient 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 anaesthetics or other materials including commercial artificial tears (in the opinion of the investigator)
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:
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 Intra Uterine Device (IUD) - during the entire course of and 30 days after the study treatment periods
Any concurrent medical condition, that in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient's well-being
Use of topical cyclosporine, topical corticosteroids or any other topical drug for the treatment of dry eye in either eye within 30 days of study enrolment.
Contact lenses or punctum plug use during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)
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 6 months
Participation in another clinical trial study at the same time as the present study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Flavio Mantelli, MD
Organizational Affiliation
Dompé Farmaceutici SpA
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
William Lipsky, MD
Organizational Affiliation
Advanced Laser Vision Surgical Institute (Study Site) Intouch Clinical Research Center (SMO)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Global Research Management
City
Glendale
State/Province
California
ZIP/Postal Code
91204
Country
United States
Facility Name
Eye Research Foundation
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Martel Eye Medical Group
City
Rancho Cordova
State/Province
California
ZIP/Postal Code
95670
Country
United States
Facility Name
Sierra Clinical Trials & Research Organization
City
Santa Ana
State/Province
California
ZIP/Postal Code
92647
Country
United States
Facility Name
Clayton Eye Clinical Research, LLC
City
Morrow
State/Province
Georgia
ZIP/Postal Code
30260
Country
United States
Facility Name
Kentucky Eye Institute
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40517
Country
United States
Facility Name
Tauber Eye Center
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Moyes Eye Center
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64154
Country
United States
Facility Name
SightMD
City
Babylon
State/Province
New York
ZIP/Postal Code
11702
Country
United States
Facility Name
Toyos Clinic
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37027
Country
United States
Facility Name
Houston Eye Associates HEA - Gramercy Location
City
Houston
State/Province
Texas
ZIP/Postal Code
77025
Country
United States
Facility Name
Advanced Laser Vision Surgical Institute (Study Site) Intouch Clinical Research Center (SMO)
City
Houston
State/Province
Texas
ZIP/Postal Code
77034
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye
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