Dry Eye Syndrome
Conditions
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.
Interventions
DRUGrhNGF 20 μg/ml
one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)
DRUGrhNGF 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.
OTHERVehicle
one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Sponsors
Dompé Farmaceutici S.p.A
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double masked
Intervention model description
Parallel groups
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged ≥ 18 years 2. Patients with moderate to severe dry eye characterized by the following clinical features: 1. Corneal and/or conjunctival staining with fluorescein using National Eye Institute (NEI) grading system \> 3 2. SANDE questionnaire \>25 mm 3. Schirmer test I (without anaesthesia) \>2mm \<10 mm/5 minutes 4. Tear film break-up time (TFBUT) \< 10 seconds in the worse eye 3. The same eye (eligible eye) must fulfill all the above criteria 4. 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) 5. 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 6. If a female of childbearing potential, have a negative pregnancy test 7. 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 8. Patients must have the ability and willingness to comply with study procedures.
Exclusion criteria
1. 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; 2. Evidence of an active ocular infection, in either eye 3. Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study 4. History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye 5. Intraocular inflammation defined as Tyndall score \>0 6. History of malignancy in the last 5 years 7. 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 8. 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) 9. 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: 1. are currently pregnant or, 2. have a positive result at the urine pregnancy test (Baseline/Day 0) or, 3. intend to become pregnant during the study treatment period or, 4. are breast-feeding or, 5. are not willing to use highly effective birth control measures, such as: hormonal contraceptives - oral, implanted, transdermal, or injected - and/or mechanical barrier methods - spermicide in conjunction with a barrier such as a condom or diaphragm or Intra Uterine Device (IUD) - during the entire course of and 30 days after the study treatment periods 10. 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 11. 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. 12. Contact lenses or punctum plug use during the study (previous use not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set | Baseline, week 4 | 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 | Baseline, week 4 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Full Analysis Set | Baseline, week 4 | 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 | Baseline, week 4 | 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 | Baseline, week 4 | 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 | Baseline, week 4 | 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 | Baseline, week 4 | 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 | Baseline, week 4 | 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 | Baseline, week 4 | 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 | Baseline, week 4 | 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 Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Full Analysis Set | Baseline, week 4 | 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. |
| Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Per Protocol Set | At week 4 | 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 | At weeks 4, 8, 12 and 16 | 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. 1. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items. 2. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops. 3. 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 | At weeks 4, 8, 12 and 16 | 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. 1. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items. 2. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops. 3. 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 | At baseline and weeks 4, 8, 12 and 16 | 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 | At weeks 4, 8, 12 and 16 | 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 | At weeks 4, 8, 12 and 16 | 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 | Aat baseline and weeks 4, 8, 12 and 16 | 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. |
| Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Full Analysis Set | At week 4 | 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 Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Per Protocol Set | Baseline, week 4 | 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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) | 81 |
| 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. | 82 |
| 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) | 84 |
| Total | 247 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 4 | 3 |
| Overall Study | Lost to Follow-up | 2 | 1 | 0 |
| Overall Study | unknow | 4 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Vehicle TID | Total | rhNGF 20 μg/ml BID + Vehicle OD | rhNGF 20 μg/ml TID |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 81 Participants | 28 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 61 Participants | 166 Participants | 54 Participants | 51 Participants |
| Age, Continuous | 59.1 years STANDARD_DEVIATION 11.5 | 60.4 years STANDARD_DEVIATION 12.49 | 60.2 years STANDARD_DEVIATION 12.39 | 62.0 years STANDARD_DEVIATION 13.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 37 Participants | 9 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 210 Participants | 73 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 84 participants | 247 participants | 82 participants | 81 participants |
| Sex: Female, Male Female | 72 Participants | 198 Participants | 69 Participants | 57 Participants |
| Sex: Female, Male Male | 12 Participants | 49 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 85 | 0 / 84 | 0 / 88 | 0 / 85 | 0 / 84 | 0 / 88 |
| other Total, other adverse events | 65 / 85 | 60 / 84 | 26 / 88 | 19 / 85 | 19 / 84 | 18 / 88 |
| serious Total, serious adverse events | 0 / 85 | 0 / 84 | 0 / 88 | 1 / 85 | 0 / 84 | 1 / 88 |
Outcome results
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
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set | 2.60 mm | Standard Error 0.77 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set | 3.99 mm | Standard Error 0.76 |
| Vehicle TID | Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set | 1.68 mm | Standard Error 0.75 |
Comparison: 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.p-value: 0.07895% CI: [-1.47, 3.32]ANOVA
Comparison: 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.p-value: 0.06695% CI: [-0.08, 4.7]ANOVA
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
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Per Protocol Set | 2.99 mm | Standard Error 0.78 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Per Protocol Set | 3.72 mm | Standard Error 0.79 |
| Vehicle TID | Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Per Protocol Set | 1.28 mm | Standard Error 0.74 |
p-value: 0.03295% CI: [-0.7, 4.12]ANOVA
p-value: 0.02995% CI: [0.02, 4.86]ANOVA
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.
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set | corneal score | -1.9 score on a scale | Standard Error 2.84 |
| rhNGF 20 μg/ml TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set | corneal and conjunctival total score | -3.75 score on a scale | Standard Error 0.63 |
| rhNGF 20 μg/ml TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set | conjunctiva score | -2.1 score on a scale | Standard Error 3.17 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set | corneal score | -1.8 score on a scale | Standard Error 2.72 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set | corneal and conjunctival total score | -2.95 score on a scale | Standard Error 0.62 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set | conjunctiva score | -1.2 score on a scale | Standard Error 3.58 |
| Vehicle TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set | corneal and conjunctival total score | -2.60 score on a scale | Standard Error 0.61 |
| Vehicle TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set | conjunctiva score | -1.4 score on a scale | Standard Error 3.36 |
| Vehicle TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set | corneal score | -1.5 score on a scale | Standard Error 2.92 |
Comparison: The secondary 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.~p value for total corneal ancd conjunctival score is reported.p-value: 0.79995% CI: [-3.11, 0.8]ANOVA
Comparison: The secondary 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.p-value: 0.71595% CI: [-2.3, 1.59]ANOVA
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.
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set | Corneal score | -1.9 score on a scale | Standard Error 2.8 |
| rhNGF 20 μg/ml TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set | Total score | -3.94 score on a scale | Standard Error 0.6 |
| rhNGF 20 μg/ml TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set | Conjunctival score | -1.9 score on a scale | Standard Error 2.95 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set | Corneal score | -1.8 score on a scale | Standard Error 2.61 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set | Total score | -2.61 score on a scale | Standard Error 0.61 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set | Conjunctival score | -1.0 score on a scale | Standard Error 3.05 |
| Vehicle TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set | Total score | -2.40 score on a scale | Standard Error 0.57 |
| Vehicle TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set | Conjunctival score | -1.3 score on a scale | Standard Error 3.32 |
| Vehicle TID | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set | Corneal score | -1.5 score on a scale | Standard Error 2.85 |
Comparison: The secondary 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.~p value for total corneal ancd conjunctival score is reported.p-value: 0.83195% CI: [-3.4, 0.31]ANOVA
Comparison: The secondary 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.~p value for total corneal ancd conjunctival score is reported.p-value: 0.7595% CI: [-2.07, 1.66]ANOVA
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.
Time frame: At weeks 4, 8, 12 and 16
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 4 | 1.2 score on a scale | Standard Deviation 9.91 |
| rhNGF 20 μg/ml TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 8 | 2.7 score on a scale | Standard Deviation 10.41 |
| rhNGF 20 μg/ml TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 12 | 3.0 score on a scale | Standard Deviation 10.1 |
| rhNGF 20 μg/ml TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 16 | 3.0 score on a scale | Standard Deviation 13.04 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 16 | 4.8 score on a scale | Standard Deviation 11.92 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 4 | 3.8 score on a scale | Standard Deviation 10.28 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 12 | 3.0 score on a scale | Standard Deviation 7.8 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 8 | 2.4 score on a scale | Standard Deviation 8.92 |
| Vehicle TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 16 | 2.0 score on a scale | Standard Deviation 11.71 |
| Vehicle TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 8 | 2.1 score on a scale | Standard Deviation 8.86 |
| Vehicle TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 12 | 3.0 score on a scale | Standard Deviation 8.59 |
| Vehicle TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set | week 4 | 2.8 score on a scale | Standard Deviation 8.86 |
Comparison: statistical analysis at week 4p-value: 0.28295% CI: [-1, 3.3]ANOVA
Comparison: statistical analysis at week 4p-value: 0.49795% CI: [1.7, 6]ANOVA
Comparison: statistical analysis at week 8p-value: 0.73495% CI: [0.5, 4.8]ANOVA
Comparison: statistical analysis at week 8p-value: 0.96395% CI: [0.1, 4.3]ANOVA
Comparison: statistical analysis at week 12p-value: 0.85495% CI: [0.7, 4.8]ANOVA
Comparison: statistical analysis at week 12p-value: 0.88195% CI: [0.8, 4.8]ANOVA
Comparison: statistical analysis at week 16p-value: 0.63295% CI: [0.3, 5.7]ANOVA
Comparison: statistical analysis at week 16p-value: 0.2295% CI: [1.7, 7]ANOVA
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.
Time frame: Aat baseline and weeks 4, 8, 12 and 16
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 4 | 1.2 score on a scale | Standard Deviation 9.98 |
| rhNGF 20 μg/ml TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 8 | 2.7 score on a scale | Standard Deviation 10.67 |
| rhNGF 20 μg/ml TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 12 | 3.6 score on a scale | Standard Deviation 9.77 |
| rhNGF 20 μg/ml TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 16 | 3.3 score on a scale | Standard Deviation 13.24 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 16 | 4.7 score on a scale | Standard Deviation 8.84 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 4 | 3.6 score on a scale | Standard Deviation 8.12 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 12 | 3.4 score on a scale | Standard Deviation 5 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 8 | 2.3 score on a scale | Standard Deviation 9.02 |
| Vehicle TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 16 | 1.9 score on a scale | Standard Deviation 11.9 |
| Vehicle TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 8 | 2.2 score on a scale | Standard Deviation 8.79 |
| Vehicle TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 12 | 3.0 score on a scale | Standard Deviation 8.71 |
| Vehicle TID | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set | week 4 | 2.8 score on a scale | Standard Deviation 8.99 |
Comparison: statistical analysis at week 4p-value: 0.29695% CI: [-0.9, 3.3]ANOVA
Comparison: statistical analysis at week 4p-value: 0.5795% CI: [1.5, 5.7]ANOVA
Comparison: statistical analysis at week 8p-value: 0.75495% CI: [0.5, 4.9]ANOVA
Comparison: statistical analysis at week 8p-value: 0.97295% CI: [0, 4.5]ANOVA
Comparison: statistical analysis at week 12p-value: 0.79395% CI: [1.4, 5.3]ANOVA
Comparison: statistical analysis at week 12p-value: 0.76695% CI: [1.5, 5.3]ANOVA
Comparison: statistical analysis at week 16p-value: 0.45895% CI: [0.6, 6]ANOVA
Comparison: statistical analysis at week 16p-value: 0.14795% CI: [2, 7.3]ANOVA
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. 1. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items. 2. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops. 3. 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 16 | 16.0 score on a scale | Standard Deviation 18.54 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 16 | -19.9 score on a scale | Standard Deviation 15.62 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 16 | 14.2 score on a scale | Standard Deviation 20.05 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 4 | 16.5 score on a scale | Standard Deviation 20.71 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 4 | 16.3 score on a scale | Standard Deviation 27.13 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 12 | 15.7 score on a scale | Standard Deviation 21.1 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 8 | 16.8 score on a scale | Standard Deviation 23.49 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 8 | 16.2 score on a scale | Standard Deviation 21.33 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 12 | 10.3 score on a scale | Standard Deviation 22.71 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 4 | 14.6 score on a scale | Standard Deviation 22.78 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 16 | 10.8 score on a scale | Standard Deviation 20.65 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 8 | 18.0 score on a scale | Standard Deviation 24.94 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 12 | -19.6 score on a scale | Standard Deviation 17.41 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 12 | 16.4 score on a scale | Standard Deviation 22.39 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 16 | 16.3 score on a scale | Standard Deviation 20.75 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 12 | 14.2 score on a scale | Standard Deviation 18.66 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 4 | 14.5 score on a scale | Standard Deviation 21.18 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 4 | 24.1 score on a scale | Standard Deviation 30.81 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 8 | 28.8 score on a scale | Standard Deviation 28.56 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 12 | 26.1 score on a scale | Standard Deviation 30.3 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 8 | -21.2 score on a scale | Standard Deviation 19.56 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 16 | 26.1 score on a scale | Standard Deviation 26.62 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 8 | 10.6 score on a scale | Standard Deviation 20.61 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 4 | -16.8 score on a scale | Standard Deviation 17.8 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 4 | 20.6 score on a scale | Standard Deviation 24.29 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 16 | 15.5 score on a scale | Standard Deviation 19.17 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 4 | 16.3 score on a scale | Standard Deviation 20.4 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 12 | 20.9 score on a scale | Standard Deviation 22.05 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 16 | 20.9 score on a scale | Standard Deviation 20.83 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 12 | 19.1 score on a scale | Standard Deviation 27.86 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 12 | -18.2 score on a scale | Standard Deviation 17.3 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 8 | 19.1 score on a scale | Standard Deviation 26.9 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 4 | 19.5 score on a scale | Standard Deviation 17.55 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 16 | 23.5 score on a scale | Standard Deviation 29.29 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 4 | 16.8 score on a scale | Standard Deviation 25 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 8 | 6.5 score on a scale | Standard Deviation 26.56 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 12 | 8.7 score on a scale | Standard Deviation 24.91 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 8 | 14.8 score on a scale | Standard Deviation 18.07 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 12 | 15.5 score on a scale | Standard Deviation 20.01 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 16 | 14.4 score on a scale | Standard Deviation 21.23 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 8 | 13.4 score on a scale | Standard Deviation 18.64 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 12 | 15.3 score on a scale | Standard Deviation 17.95 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 8 | 18.3 score on a scale | Standard Deviation 19 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 4 | 19.0 score on a scale | Standard Deviation 30.57 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 16 | 8.1 score on a scale | Standard Deviation 23.88 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 4 | -17.7 score on a scale | Standard Deviation 16.54 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 8 | -16.6 score on a scale | Standard Deviation 15.46 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 16 | -19.1 score on a scale | Standard Deviation 17.75 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 4 | -16.5 score on a scale | Standard Deviation 17.04 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 16 | 9.4 score on a scale | Standard Deviation 16.74 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 16 | 16.0 score on a scale | Standard Deviation 21.63 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 12 | 14.2 score on a scale | Standard Deviation 18.2 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 16 | -11.1 score on a scale | Standard Deviation 14.46 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 16 | 13.5 score on a scale | Standard Deviation 20.22 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 8 | -13.5 score on a scale | Standard Deviation 15.01 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 8 | 17.0 score on a scale | Standard Deviation 22.52 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 12 | 17.8 score on a scale | Standard Deviation 22.35 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 8 | 12.7 score on a scale | Standard Deviation 17.69 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 4 | 24.1 score on a scale | Standard Deviation 33.57 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 4 | 13.8 score on a scale | Standard Deviation 27.19 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | work limitations - change from baseline to week 4 | 17.4 score on a scale | Standard Deviation 24.09 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 8 | 4.8 score on a scale | Standard Deviation 26.59 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 16 | 12.7 score on a scale | Standard Deviation 27.03 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Dry eye symptom bother - change from baseline to week 12 | -13.0 score on a scale | Standard Deviation 13.01 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 12 | 9.0 score on a scale | Standard Deviation 27.95 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 12 | 15.0 score on a scale | Standard Deviation 26.83 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | treatment-related bother - change from baseline to week 16 | 10.0 score on a scale | Standard Deviation 27.14 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 8 | 11.2 score on a scale | Standard Deviation 17.54 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 4 | 13.1 score on a scale | Standard Deviation 20.6 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Emotional well-being - change from baseline to week 4 | 15.0 score on a scale | Standard Deviation 20.47 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Daily activity limitations - Chance from baseline to week 12 | 11.1 score on a scale | Standard Deviation 17.45 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set | Treatment satisfaction/happiness - change from baseline to week 8 | 13.3 score on a scale | Standard Deviation 30.69 |
Comparison: Work Limitations - change from baseline to week 16p-value: 0.56495% CI: [11.6, 25]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 4p-value: 0.28995% CI: [12, 20.8]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 4p-value: 0.03295% CI: [15.4, 24]ANOVA
Comparison: Daily Activity Limitations - change to baseline to week 8p-value: 0.09595% CI: [11.9, 20.8]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 8p-value: 0.28295% CI: [10.1, 18.8]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 12p-value: 0.16995% CI: [10.6, 19.4]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 12p-value: 0.12995% CI: [11.1, 19.7]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 16p-value: 0.11195% CI: [9.7, 18.4]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 16p-value: 0.10795% CI: [9.7, 18.3]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 4p-value: 0.82795% CI: [9.7, 18.9]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 4p-value: 0.68895% CI: [11.8, 20.8]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 8p-value: 0.32495% CI: [11.4, 20]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 8p-value: 0.94995% CI: [8.7, 17.1]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 12p-value: 0.92795% CI: [11.4, 20.1]ANOVA
Comparison: Work Limitations - change from baseline to week 16p-value: 0.2595% CI: [14.1, 27.8]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 12p-value: 0.77695% CI: [10.8, 18.8]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 16p-value: 0.41895% CI: [11.4, 20.1]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 16p-value: 0.61395% CI: [10.6, 19]ANOVA
Comparison: Work Limitations - change from baseline to week 4p-value: 0.72195% CI: [8.3, 23.2]ANOVA
Comparison: Work Limitations - change from baseline to week 4p-value: 0.55895% CI: [13.1, 28]ANOVA
Comparison: Work Limitations - change from baseline to week 8p-value: 0.80995% CI: [11.5, 25.3]ANOVA
Comparison: Work Limitations - change from baseline to week 8p-value: 0.65195% CI: [12.4, 26.4]ANOVA
Comparison: Work Limitations - change from baseline to week 12p-value: 0.76995% CI: [9.5, 23.3]ANOVA
Comparison: Work Limitations - change from baseline to week 12p-value: 0.45495% CI: [14.3, 28.3]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 4p-value: 0.85395% CI: [15.6, 32.2]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 4p-value: 0.39395% CI: [11.9, 28]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 8p-value: 0.0195% CI: [20.2, 35.6]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 8p-value: 0.39595% CI: [11.1, 25.4]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 12p-value: 0.06895% CI: [17.1, 32.4]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 12p-value: 0.495% CI: [12.2, 26.4]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 16p-value: 0.02195% CI: [18.1, 33]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 16p-value: 0.05695% CI: [16.1, 30]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 4p-value: 0.98195% CI: [7.6, 20.7]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 4p-value: 0.52595% CI: [11.1, 22.9]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 8p-value: 0.35695% CI: [2.9, 16]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 8p-value: 0.77195% CI: [0.7, 12.4]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 12p-value: 0.92695% CI: [2, 15.5]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 12p-value: 0.77895% CI: [1.9, 13.9]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 16p-value: 0.984ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 16p-value: 0.51495% CI: [1.6, 13.1]ANOVA
Comparison: Symptom Bother - change from baseline to week 4p-value: 0.98595% CI: [-20.4, -12.8]ANOVA
Comparison: Symptom Bother - change from baseline to week 4p-value: 0.64695% CI: [-21.5, -14]ANOVA
Comparison: Symptom Bother - change from baseline to week 8p-value: 0.00795% CI: [-24.5, -16.9]ANOVA
Comparison: Symptom Bother - change from baseline to week 8p-value: 0.30595% CI: [-19.9, -12.5]ANOVA
Comparison: Symptom Bother - change from baseline to week 12p-value: 0.01595% CI: [-22.7, -15.4]ANOVA
Comparison: Symptom Bother - change from baseline to week 12p-value: 0.03995% CI: [-21.5, -14.4]ANOVA
p-value: 0.00195% CI: [-23.3, -16]ANOVA
Comparison: Symptom Bother - change from baseline to week 16p-value: 0.00295% CI: [-22.4, -15.3]ANOVA
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. 1. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items. 2. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops. 3. 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 16 | 13.9 score on a scale | Standard Deviation 19.33 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 16 | 26.0 score on a scale | Standard Deviation 27.6 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 4 | 15.2 score on a scale | Standard Deviation 21.73 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 4 | -17.3 score on a scale | Standard Deviation 17.19 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 12 | 25.8 score on a scale | Standard Deviation 31.16 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 4 | 16.0 score on a scale | Standard Deviation 27.48 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 16 | 16.8 score on a scale | Standard Deviation 18.48 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 8 | 30.1 score on a scale | Standard Deviation 28.47 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 4 | 25.4 score on a scale | Standard Deviation 31.05 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 12 | 15.0 score on a scale | Standard Deviation 21.67 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 8 | 16.9 score on a scale | Standard Deviation 21.7 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 16 | 15.4 score on a scale | Standard Deviation 19.43 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 8 | 17.4 score on a scale | Standard Deviation 25.13 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 12 | -19.6 score on a scale | Standard Deviation 17.41 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 16 | 11.4 score on a scale | Standard Deviation 20.9 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 12 | 9.9 score on a scale | Standard Deviation 22.83 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 8 | 17.1 score on a scale | Standard Deviation 23.93 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 4 | 16.8 score on a scale | Standard Deviation 21.2 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 12 | 15.1 score on a scale | Standard Deviation 18.58 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 8 | 11.6 score on a scale | Standard Deviation 20.73 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 16 | -20.6 score on a scale | Standard Deviation 15.21 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 4 | 15.7 score on a scale | Standard Deviation 22.66 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 12 | 17.0 score on a scale | Standard Deviation 20.3 |
| rhNGF 20 μg/ml TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 8 | -21.5 score on a scale | Standard Deviation 18.88 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 8 | 6.9 score on a scale | Standard Deviation 25.46 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 12 | 16.4 score on a scale | Standard Deviation 16.87 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 16 | 16.6 score on a scale | Standard Deviation 18.59 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 4 | 21.3 score on a scale | Standard Deviation 24.83 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 8 | 18.3 score on a scale | Standard Deviation 19.43 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 4 | 19.7 score on a scale | Standard Deviation 17.58 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 8 | 15.3 score on a scale | Standard Deviation 16.85 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 12 | 16.5 score on a scale | Standard Deviation 18.45 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 16 | 15.8 score on a scale | Standard Deviation 19.74 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 4 | 17.3 score on a scale | Standard Deviation 20.33 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 8 | 13.9 score on a scale | Standard Deviation 18.34 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 12 | 21.9 score on a scale | Standard Deviation 21.82 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 16 | 21.9 score on a scale | Standard Deviation 20.93 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 4 | 19.6 score on a scale | Standard Deviation 31.26 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 8 | 21.0 score on a scale | Standard Deviation 27.85 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 12 | 21.6 score on a scale | Standard Deviation 27.82 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 16 | 24.3 score on a scale | Standard Deviation 28.26 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 4 | 15.3 score on a scale | Standard Deviation 23.39 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 12 | 10.0 score on a scale | Standard Deviation 23.05 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 16 | 9.5 score on a scale | Standard Deviation 21.62 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 4 | -18.7 score on a scale | Standard Deviation 16.64 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 8 | -17.6 score on a scale | Standard Deviation 15.4 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 12 | -19.7 score on a scale | Standard Deviation 17.16 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 16 | -20.7 score on a scale | Standard Deviation 17.66 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 16 | 13.2 score on a scale | Standard Deviation 27.18 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 8 | 11.5 score on a scale | Standard Deviation 17.47 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 12 | 11.2 score on a scale | Standard Deviation 17.64 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 4 | 14.4 score on a scale | Standard Deviation 27.71 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 4 | 13.0 score on a scale | Standard Deviation 20.63 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 8 | -13.9 score on a scale | Standard Deviation 14.97 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 8 | 4.6 score on a scale | Standard Deviation 26.78 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 4 | 25.2 score on a scale | Standard Deviation 33.81 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 8 | 13.2 score on a scale | Standard Deviation 17.55 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 12 | 8.7 score on a scale | Standard Deviation 28.26 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 12 | 18.6 score on a scale | Standard Deviation 22.14 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 16 | -11.3 score on a scale | Standard Deviation 14.61 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | treatment-related bother - change from baseline to week 16 | 9.8 score on a scale | Standard Deviation 27.51 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 16 | 16.7 score on a scale | Standard Deviation 21.8 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 8 | 17.9 score on a scale | Standard Deviation 22.29 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 16 | 14.2 score on a scale | Standard Deviation 20.11 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | work limitations - change from baseline to week 4 | 18.4 score on a scale | Standard Deviation 24.23 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 12 | -13.2 score on a scale | Standard Deviation 13.18 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 8 | 13.9 score on a scale | Standard Deviation 30.66 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 4 | 15.8 score on a scale | Standard Deviation 20.6 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Dry eye symptom bother - change from baseline to week 4 | -17.2 score on a scale | Standard Deviation 17.1 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Treatment satisfaction/happiness - change from baseline to week 12 | 15.5 score on a scale | Standard Deviation 26.81 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Daily activity limitations - Change from baseline to week 16 | 9.4 score on a scale | Standard Deviation 16.94 |
| Vehicle TID | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set | Emotional well-being - change from baseline to week 12 | 14.7 score on a scale | Standard Deviation 18.14 |
Comparison: Daily Activity Limitations - change from baseline to week 4p-value: 0.24195% CI: [12.2, 21.4]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 4p-value: 0.0495% CI: [15.1, 24.4]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 8p-value: 0.09795% CI: [12.3, 21.4]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 8p-value: 0.23895% CI: [10.7, 19.9]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 12p-value: 0.0795% CI: [12, 20.9]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 12p-value: 0.05895% CI: [12.3, 21.1]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 16p-value: 0.12895% CI: [9.3, 18.1]ANOVA
Comparison: Daily Activity Limitations - change from baseline to week 16p-value: 0.02495% CI: [11.6, 20.3]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 4p-value: 0.86595% CI: [10.4, 20.1]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 4p-value: 0.66295% CI: [12.4, 22.2]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 8p-value: 0.26695% CI: [12.2, 21.1]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 8p-value: 0.82495% CI: [9.4, 18.3]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 12p-value: 0.88395% CI: [10.6, 19]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 12p-value: 0.51695% CI: [12.1, 20.4]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 16p-value: 0.40795% CI: [12.1, 21]ANOVA
Comparison: Emotional Well-Being - change from baseline to week 16p-value: 0.42295% CI: [12, 20.9]ANOVA
Comparison: Work Limitations - change from baseline to week 4p-value: 0.61595% CI: [8.1, 23.8]ANOVA
Comparison: Work Limitations - change from baseline to week 4p-value: 0.62695% CI: [13.3, 29.2]ANOVA
Comparison: Work Limitations - change from baseline to week 8p-value: 0.96895% CI: [11.1, 25.6]ANOVA
p-value: 0.68995% CI: [12.8, 27.4]ANOVA
Comparison: Work Limitations - change from baseline to week 12p-value: 0.52895% CI: [8.5, 22.7]ANOVA
Comparison: Work Limitations - change from baseline to week 12p-value: 0.36895% CI: [15.8, 30.1]ANOVA
Comparison: Work Limitations - change from baseline to week 16p-value: 0.76495% CI: [10.7, 24.7]ANOVA
Comparison: Work Limitations - change from baseline to week 16p-value: 0.18495% CI: [15.5, 29.6]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 4p-value: 0.90995% CI: [16.5, 34.2]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 4p-value: 0.42895% CI: [12.2, 30]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 8p-value: 0.00895% CI: [21.6, 37.9]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 8p-value: 0.22295% CI: [13.5, 29.2]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 12p-value: 0.08295% CI: [17.2, 33.4]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 12p-value: 0.15495% CI: [15.6, 31.1]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 16p-value: 0.0395% CI: [18, 33.6]ANOVA
Comparison: Treatment Satisfaction - change from baseline to week 16p-value: 0.04695% CI: [17.1, 32.1]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 4p-value: 0.86195% CI: [8.6, 22.2]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 4p-value: 0.86595% CI: [9, 21.7]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 8p-value: 0.27895% CI: [3.6, 17.3]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 8p-value: 0.68995% CI: [0.9, 13.5]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 12p-value: 0.99395% CI: [2.1, 16.2]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 12p-value: 0.98995% CI: [2.8, 15.7]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 16p-value: 0.97695% CI: [3.7, 17]ANOVA
Comparison: Treatment-Related Bother - change from baseline to week 16p-value: 0.77895% CI: [2.9, 15.1]ANOVA
Comparison: Symptom Bother - change from baseline to week 4p-value: 0.96495% CI: [-21.2, -13.3]ANOVA
Comparison: Symptom Bother - change from baseline to week 4p-value: 0.58195% CI: [-22.7, -14.7]ANOVA
Comparison: Symptom Bother - change from baseline to week 8p-value: 0.00695% CI: [-25.2, -17.5]ANOVA
Comparison: Symptom Bother - change from baseline to week 8p-value: 0.17595% CI: [-21.4, -13.7]ANOVA
Comparison: Symptom Bother - change from baseline to week 12p-value: 0.01695% CI: [-23.1, -15.6]ANOVA
Comparison: Symptom Bother - change from baseline to week 12p-value: 0.0195% CI: [-23.5, -16.1]ANOVA
Comparison: Symptom Bother - change from baseline to week 16p-value: 095% CI: [-24.3, -16.8]ANOVA
Comparison: Symptom Bother - change from baseline to week 16p-value: 095% CI: [-24.6, -17.1]ANOVA
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
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Full Analysis Set | 2.19 mm | Standard Error 0.69 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Full Analysis Set | 0.89 mm | Standard Error 0.69 |
| Vehicle TID | Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Full Analysis Set | 0.21 mm | Standard Error 0.68 |
Comparison: The secondary 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.p-value: 0.02595% CI: [-0.19, 4.13]ANOVA
Comparison: The secondary 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.p-value: 0.24395% CI: [-1.48, 2.83]ANOVA
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
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Per Protocol Set | 2.24 mm | Standard Error 0.69 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Per Protocol Set | 0.54 mm | Standard Error 0.7 |
| Vehicle TID | Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Per Protocol Set | -0.18 mm | Standard Error 0.66 |
p-value: 0.00795% CI: [0.28, 4.54]ANOVA
p-value: 0.2395% CI: [-1.43, 2.85]ANOVA
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
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Full Analysis Set | -24.9 score on a scale | Standard Deviation 26.29 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Full Analysis Set | -22.7 score on a scale | Standard Deviation 25.42 |
| Vehicle TID | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Full Analysis Set | -24.0 score on a scale | Standard Deviation 23.81 |
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.
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Per Protocol Set | -24.7 score on a scale | Standard Deviation 26.73 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Per Protocol Set | -22.2 score on a scale | Standard Deviation 25.67 |
| Vehicle TID | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Per Protocol Set | -23.8 score on a scale | Standard Deviation 23.92 |
p-value: 0.81t-test, 2 sided
p-value: 0.733t-test, 2 sided
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.
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Full Analysis Set | -24.6 score on a scale | Standard Deviation 27.15 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Full Analysis Set | -20.3 score on a scale | Standard Deviation 24.91 |
| Vehicle TID | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Full Analysis Set | -22.2 score on a scale | Standard Deviation 22.29 |
p-value: 0.534t-test, 2 sided
p-value: 0.611t-test, 2 sided
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.
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Per Protocol Set | -24.9 score on a scale | Standard Deviation 27.35 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Per Protocol Set | -19.9 score on a scale | Standard Deviation 25.34 |
| Vehicle TID | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Per Protocol Set | -22.1 score on a scale | Standard Deviation 21.74 |
p-value: 0.486t-test, 2 sided
p-value: 0.564t-test, 2 sided
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.
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Full Analysis Set | 1.11 seconds | Standard Error 0.25 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Full Analysis Set | 0.43 seconds | Standard Error 0.25 |
| Vehicle TID | Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Full Analysis Set | 0.15 seconds | Standard Error 0.25 |
p-value: 0.00495% CI: [0.17, 1.75]ANOVA
p-value: 0.21795% CI: [-0.51, 1.07]ANOVA
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.
Time frame: Baseline, week 4
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Per Protocol Set | 1.11 seconds | Standard Error 0.27 |
| rhNGF 20 μg/ml BID + Vehicle OD | Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Per Protocol Set | 0.47 seconds | Standard Error 0.27 |
| Vehicle TID | Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Per Protocol Set | 0.19 seconds | Standard Error 0.25 |
p-value: 0.00795% CI: [0.1, 1.74]ANOVA
p-value: 0.22595% CI: [-0.54, 1.1]ANOVA
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.
Time frame: At week 4
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhNGF 20 μg/ml TID | Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Full Analysis Set | 2 Participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Full Analysis Set | 9 Participants |
| Vehicle TID | Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Full Analysis Set | 3 Participants |
p-value: 0.68t-test, 2 sided
p-value: 0.066t-test, 2 sided
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.
Time frame: At week 4
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhNGF 20 μg/ml TID | Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Per Protocol Set | 0 Participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Per Protocol Set | 8 Participants |
| Vehicle TID | Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Per Protocol Set | 3 Participants |
p-value: 0.097Chi-squared
p-value: 0.076Chi-squared
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.
Time frame: At baseline and weeks 4, 8, 12 and 16
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - Very much improved | 9 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - Much Improved | 18 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - minimally worse | 5 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - much improved | 23 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - very much worse | 0 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - minimally improved | 22 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - much improved | 16 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - no change | 21 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - minimally worse | 2 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - very much improved | 11 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - minimally worse | 1 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - Minimally improved | 18 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - very much worse | 1 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - much worse | 0 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - no change | 15 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - no change | 19 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - no change | 24 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - minimally improved | 19 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - minimally improved | 22 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - minimally worse | 6 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - much worse | 1 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - much improved | 24 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - much worse | 1 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - very much worse | 2 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - very much improved | 7 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - very much worse | 0 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - Very Much Improved | 11 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - much worse | 2 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - no change | 33 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - minimally improved | 21 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - no change | 36 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - Very Much Improved | 2 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - Much Improved | 15 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - Minimally improved | 21 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - no change | 38 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - minimally worse | 4 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - much worse | 1 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - very much worse | 0 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - Very much improved | 3 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - much improved | 11 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - no change | 37 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - minimally worse | 4 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - much worse | 1 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - very much worse | 1 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - very much improved | 3 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - much improved | 10 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - minimally improved | 24 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - minimally worse | 1 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - much worse | 2 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - very much worse | 1 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - very much improved | 3 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - much improved | 19 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - minimally improved | 20 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - minimally worse | 2 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - much worse | 0 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - very much worse | 1 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - Very much improved | 1 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - Much Improved | 20 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - minimally worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - very much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - minimally improved | 24 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - minimally worse | 5 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - very much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - much worse | 2 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - very much improved | 6 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - minimally worse | 2 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - very much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - much improved | 16 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - no change | 38 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - much worse | 2 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - minimally worse | 2 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - minimally improved | 19 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - very much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - no change | 46 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - Minimally improved | 20 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - very much improved | 4 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - minimally improved | 17 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 4 - Very Much Improved | 4 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - much improved | 12 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 8 - much improved | 16 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 16 - no change | 36 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Full Analysis Set | week 12 - no change | 40 participants |
Comparison: at week 4p-value: 0.302Wilcoxon (Mann-Whitney)
Comparison: at week 4p-value: 0.224Wilcoxon (Mann-Whitney)
Comparison: at week 8 (FUP)p-value: 0Wilcoxon (Mann-Whitney)
Comparison: at week 8 (FUP)p-value: 0.885Wilcoxon (Mann-Whitney)
Comparison: At week 12 (FUP)p-value: 0.035Wilcoxon (Mann-Whitney)
Comparison: At week 12 (FUP)p-value: 0.698Wilcoxon (Mann-Whitney)
Comparison: At week 16 (FUP)p-value: 0.016Wilcoxon (Mann-Whitney)
Comparison: At week 16 (FUP)p-value: 0.706Wilcoxon (Mann-Whitney)
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.
Time frame: At weeks 4, 8, 12 and 16
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - minimally improved | 18 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - no change | 19 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - minimally worse | 5 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - no change | 20 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - Minimally improved | 17 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - no change | 15 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - minimally worse | 1 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - much worse | 1 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - minimally improved | 21 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - much worse | 0 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - minimally improved | 19 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - much improved | 13 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - very much worse | 0 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - no change | 20 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - very much improved | 11 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - very much worse | 0 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - much improved | 22 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - minimally worse | 6 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - Very much improved | 9 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - much worse | 0 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - very much improved | 7 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - very much worse | 0 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - Very Much Improved | 10 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - Much Improved | 18 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - very much worse | 1 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - much improved | 21 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - minimally worse | 2 participants |
| rhNGF 20 μg/ml TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - much worse | 2 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - very much worse | 0 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - Much Improved | 12 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - Very Much Improved | 2 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - Minimally improved | 19 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - no change | 34 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - minimally worse | 4 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - much worse | 0 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - very much worse | 0 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - Very much improved | 3 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - much improved | 9 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - minimally improved | 21 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - no change | 34 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - minimally worse | 3 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - much worse | 1 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - very much worse | 0 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - very much improved | 3 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - much improved | 9 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - minimally improved | 23 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - no change | 33 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - minimally worse | 1 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - much worse | 1 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - very much worse | 0 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - very much improved | 3 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - much improved | 18 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - minimally improved | 17 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - no change | 30 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - minimally worse | 2 participants |
| rhNGF 20 μg/ml BID + Vehicle OD | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - no change | 34 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - minimally worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - much improved | 15 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - Very Much Improved | 4 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - much worse | 2 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - Very much improved | 1 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - very much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - very much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - minimally worse | 5 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - very much improved | 6 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - no change | 36 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - very much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - much improved | 15 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - Minimally improved | 20 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - very much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - minimally worse | 2 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - very much improved | 4 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - much worse | 2 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - minimally improved | 18 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - much improved | 11 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - minimally worse | 2 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 4 - Much Improved | 18 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - minimally improved | 23 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - no change | 43 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 16 - much worse | 0 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 12 - no change | 38 participants |
| Vehicle TID | Patient Global Impression of Change (PGIC) - Per Protocol Set | week 8 - minimally improved | 17 participants |
Comparison: at week 4p-value: 0.21Wilcoxon (Mann-Whitney)
Comparison: at weeek 4p-value: 0.26Wilcoxon (Mann-Whitney)
Comparison: At week 8 (FUP)p-value: 0Wilcoxon (Mann-Whitney)
Comparison: at week 8 (FUP)p-value: 0.734Wilcoxon (Mann-Whitney)
Comparison: at week 12 (FUP)p-value: 0.05Wilcoxon (Mann-Whitney)
Comparison: at week 12 (FUP)p-value: 0.985Wilcoxon (Mann-Whitney)
Comparison: at week 16 (FUP)p-value: 0.018Wilcoxon (Mann-Whitney)
Comparison: at week 16 (FUP)p-value: 0.58Wilcoxon (Mann-Whitney)