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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Experimental | One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) |
|
| rhNGF 20 μg/ml BID + vehicle OD | Experimental | 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 TID | Placebo Comparator | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rhNGF 20 μg/ml | Drug | one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline, week 4 |
| 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 | Baseline, week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Male or female aged ≥ 18 years
Patients with moderate to severe dry eye characterized by the following clinical features:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Flavio Mantelli, MD, PhD | Dompé Farmaceutici SpA | Study Director |
| William Lipsky, MD | Advanced Laser Vision Surgical Institute (Study Site) Intouch Clinical Research Center (SMO) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Global Research Management | Glendale | California | 91204 | United States | ||
| Eye Research Foundation |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39020305 | Derived | Wirta D, Lipsky W, Toyos M, Martel J, Goosey J, Verachtert A, El-Harazi S, Karpecki P, Allegretti M, Goisis G, Pasedis G, Mantelli F. Recombinant human nerve growth factor (cenegermin) for moderate-to-severe dry eye: phase II, randomized, vehicle-controlled, dose-ranging trial. BMC Ophthalmol. 2024 Jul 17;24(1):290. doi: 10.1186/s12886-024-03564-w. |
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Enrollment of a total of 300 patients was planned. Due to restrictions in the hospital clinical routines related to coronavirus disease 2019, the sponsor decided to prematurely stop enrollment in the study in order to comply with quarantine measures of each country and avoid risks of infection of COVID-19 illness for all involved patients.
A total of 261 patients were randomized to receive study treatment: 87 in the rhNGF TID group, 86 in the rhNGF BID group, and 88 in the vehicle TID group.
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| ID | Title | Description |
|---|---|---|
| FG000 | rhNGF 20 μg/ml TID | One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) |
| FG001 | rhNGF 20 μg/ml BID + Vehicle OD |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 8, 2019 | Sep 9, 2021 |
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Parallel groups
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Double masked
| rhNGF 20 μg/ml + vehicle | Drug | 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. |
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| Vehicle | Other | one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
|
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| Baseline, week 4 |
| 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. | Baseline, week 4 |
| 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 | Baseline, week 4 |
| 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. | Baseline, week 4 |
| 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 | Baseline, week 4 |
| 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 | Baseline, week 4 |
| 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. | Baseline, week 4 |
| 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. | Baseline, week 4 |
| 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. | Baseline, week 4 |
| 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. | Baseline, week 4 |
| 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. | At week 4 |
| 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. | At week 4 |
| 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.
Scores for each dimensions ranged from 0 to 100. Higher scores for:
| At weeks 4, 8, 12 and 16 |
| 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.
Scores for each dimensions ranged from 0 to 100. Higher scores for:
| At weeks 4, 8, 12 and 16 |
| 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. | At baseline and weeks 4, 8, 12 and 16 |
| 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. | At weeks 4, 8, 12 and 16 |
| 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. | At weeks 4, 8, 12 and 16 |
| 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. | Aat baseline and weeks 4, 8, 12 and 16 |
| Newport Beach |
| California |
| 92663 |
| United States |
| Martel Eye Medical Group | Rancho Cordova | California | 95670 | United States |
| Sierra Clinical Trials & Research Organization | Santa Ana | California | 92647 | United States |
| Clayton Eye Clinical Research, LLC | Morrow | Georgia | 30260 | United States |
| Kentucky Eye Institute | Lexington | Kentucky | 40517 | United States |
| Tauber Eye Center | Kansas City | Missouri | 64111 | United States |
| Moyes Eye Center | Kansas City | Missouri | 64154 | United States |
| SightMD | Babylon | New York | 11702 | United States |
| Toyos Clinic | Nashville | Tennessee | 37027 | United States |
| Houston Eye Associates HEA - Gramercy Location | Houston | Texas | 77025 | United States |
| Advanced Laser Vision Surgical Institute (Study Site) Intouch Clinical Research Center (SMO) | Houston | Texas | 77034 | United States |
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) rhNGF 20 μg/ml + vehicle: 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. |
| FG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
| FAS Popuation | The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. This analysis set was used for the primary efficacy analysis. Patients were analyzed according to the randomized treatment. |
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| PP Population | The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. This analysis set was used for supportive efficacy analysis. |
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| COMPLETED |
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| NOT COMPLETED |
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Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.
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| ID | Title | Description |
|---|---|---|
| BG000 | rhNGF 20 μg/ml TID | One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) |
| BG001 | rhNGF 20 μg/ml BID + Vehicle OD | 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) rhNGF 20 μg/ml + vehicle: 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. |
| BG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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 | Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Least Squares Mean | Standard Error | mm | Baseline, week 4 |
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| Primary | 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 | Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. | Posted | Least Squares Mean | Standard Error | mm | Baseline, week 4 |
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| Secondary | 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. | Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Mean | Standard Deviation | score on a scale | Baseline, week 4 |
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| Secondary | 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. | Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. | Posted | Mean | Standard Deviation | score on a scale | Baseline, week 4 |
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| Secondary | 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 | Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Mean | Standard Deviation | score on a scale | Baseline, week 4 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. | Posted | Mean | Standard Deviation | score on a scale | Baseline, week 4 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Least Squares Mean | Standard Error | mm | Baseline, week 4 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. | Posted | Least Squares Mean | Standard Error | mm | Baseline, week 4 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, week 4 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. This analysis set was used for supportive efficacy analysis. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, week 4 |
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| Secondary | 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. | Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Least Squares Mean | Standard Error | seconds | Baseline, week 4 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. | Posted | Least Squares Mean | Standard Error | seconds | Baseline, week 4 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Count of Participants | Participants | At week 4 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. | Posted | Count of Participants | Participants | At week 4 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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.
Scores for each dimensions ranged from 0 to 100. Higher scores for:
| Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Mean | Standard Deviation | score on a scale | At weeks 4, 8, 12 and 16 |
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| Secondary | 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.
Scores for each dimensions ranged from 0 to 100. Higher scores for:
| Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. | Posted | Mean | Standard Deviation | score on a scale | At weeks 4, 8, 12 and 16 |
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| Secondary | 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. | Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Number | participants | At baseline and weeks 4, 8, 12 and 16 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. | Posted | Number | participants | At weeks 4, 8, 12 and 16 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint. | Posted | Mean | Standard Deviation | score on a scale | At weeks 4, 8, 12 and 16 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. | Posted | Mean | Standard Deviation | score on a scale | Aat baseline and weeks 4, 8, 12 and 16 |
|
From Screening day to week 16
More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | rhNGF 20 μg/ml TID - Treatment Period | One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) | 0 | 85 | 0 | 85 | 65 | 85 |
| EG001 | rhNGF 20 μg/ml BID + Vehicle OD - Treatment Period | 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) rhNGF 20 μg/ml + vehicle: 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. | 0 | 84 | 0 | 84 | 60 | 84 |
| EG002 | Vehicle TID - Treatment Period | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) | 0 | 88 | 0 | 88 | 26 | 88 |
| EG003 | rhNGF 20 μg/ml TID - Follow-up Period | One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) | 0 | 85 | 1 | 85 | 19 | 85 |
| EG004 | rhNGF 20 μg/ml BID + Vehicle OD - Follow-up Period | 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) rhNGF 20 μg/ml + vehicle: 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. | 0 | 84 | 0 | 84 | 19 | 84 |
| EG005 | Vehicle TID - Follow up Period | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) | 0 | 88 | 1 | 88 | 18 | 88 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear pain | Ear and labyrinth disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Asthenopia | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Blepharitis | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Blepharospasm | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Chalazion | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Conjunctival Disorder | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Conjunctival Haemorrhage | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Conjunctival Hyperaemia | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dry Eye | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Erythema Of Eyelid | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eye Allergy | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eye Discharge | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eye Disorder | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eye Irritation | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eye Pain | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eye Pruritus | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eye Swelling | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eyelid Disorder | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eyelid Irritation | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eyelid Oedema | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Eyelid Pain | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Foreign Body Sensation In Eyes | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Lacrimation Increased | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Meibomian Gland Dysfunction | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Ocular Discomfort | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Ocular Hyperaemia | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Photophobia | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Posterior Capsule Opacification | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Refraction Disorder | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Swelling Of Eyelid | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Vision Blurred | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Visual Acuity Reduced | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Visual Impairment | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Vitreous Floaters | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Inguinal Hernia | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Instillation Site Irritation | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Instillation Site Pain | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Kidney Infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Upper Respiratory Tract | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Viral Infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Back Injury | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Humerus Fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Ligament Sprain | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Superficial Injury Of Eye | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Migraine With Aura | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Bladder Prolapse | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Sinus Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Throat Irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hot Flush | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development & Operations | Dompé farmaceutici s.p.a. | +39 02 583831 | clinical.trials@dompe.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 8, 2019 | Sep 10, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D015352 | Dry Eye Syndromes |
| ID | Term |
|---|---|
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000647429 | cenegermin |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
The primary endpoint was analyzed using analysis of variance (ANOVA) including only treatment as the main factor, followed by preplanned comparisons from vehicle and rhNGF dosages according to Williams' procedure.
| ANOVA |
| 0.066 |
| least square mean difference |
| 2.31 |
| 2-Sided |
| 95 |
| -0.08 |
| 4.70 |
| Superiority |
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
|
|
|
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
|
|
|
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
|
|
|
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| rhNGF 20 μg/ml BID + Vehicle OD |
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) rhNGF 20 μg/ml + vehicle: 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. |
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG001 | rhNGF 20 μg/ml BID + Vehicle OD | 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) rhNGF 20 μg/ml + vehicle: 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. |
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| rhNGF 20 μg/ml BID + Vehicle OD |
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) rhNGF 20 μg/ml + vehicle: 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. |
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG001 |
| rhNGF 20 μg/ml BID + Vehicle OD |
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) rhNGF 20 μg/ml + vehicle: 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. |
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG001 |
| rhNGF 20 μg/ml BID + Vehicle OD |
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) rhNGF 20 μg/ml + vehicle: 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. |
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG001 | rhNGF 20 μg/ml BID + Vehicle OD | 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) rhNGF 20 μg/ml + vehicle: 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. |
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| Vehicle TID |
Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG002 |
| Vehicle TID |
Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| rhNGF 20 μg/ml BID + Vehicle OD |
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) rhNGF 20 μg/ml + vehicle: 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. |
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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| OG001 | rhNGF 20 μg/ml BID + Vehicle OD | 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) rhNGF 20 μg/ml + vehicle: 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. |
| OG002 | Vehicle TID | Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours) |
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