A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye
Study Details
Study Description
Brief Summary
The objective of this study is to assess the efficacy and safety of rhNGF eye drops at 20 μg/ml concentration administered two or three times daily for 4 weeks in patients with moderate to severe dry eye.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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) |
Drug: rhNGF 20 μg/ml
one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)
Other Names:
|
Experimental: 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) |
Drug: 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.
Other Names:
|
Placebo Comparator: Vehicle TID Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) |
Other: Vehicle
one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops. The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother. Scores for each dimensions ranged from 0 to 100. Higher scores for: dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities; symptom-bother dimension indicates greater bother due to symptoms; satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness; treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience.
- Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set [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. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops. The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother. Scores for each dimensions ranged from 0 to 100. Higher scores for: dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities; symptom-bother dimension indicates greater bother due to symptoms; satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness; treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience.
- Patient Global Impression of Change (PGIC) - Full Analysis Set [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female aged ≥ 18 years
-
Patients with moderate to severe dry eye characterized by the following clinical features:
-
Corneal and/or conjunctival staining with fluorescein using National Eye Institute (NEI) grading system > 3
-
SANDE questionnaire >25 mm
-
Schirmer test I (without anaesthesia) >2mm <10 mm/5 minutes
-
Tear film break-up time (TFBUT) < 10 seconds in the worse eye
-
The same eye (eligible eye) must fulfill all the above criteria
-
Patients diagnosed with dry eye at least 6 months before enrolment (current use or recommended use of artificial tears for the treatment of Dry Eye)
-
Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200 Snellen value) in both eyes at the time of study enrolment
-
If a female of childbearing potential, have a negative pregnancy test
-
Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent form signed by patients and/or legal representative must have been approved by the Institutional Review Board (IRB) / Independent Ethics Committee (IEC) for the current study
-
Patients must have the ability and willingness to comply with study procedures.
Exclusion Criteria:
-
Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments;
-
Evidence of an active ocular infection, in either eye
-
Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study
-
History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye
-
Intraocular inflammation defined as Tyndall score >0
-
History of malignancy in the last 5 years
-
Systemic disease not stabilized within 1 month before Screening Visit (e.g. diabetes with glycemia out of range, thyroid malfunction..) or judged by the investigator to be incompatible with the study (e.g. current systemic infections) or with a condition incompatible with the frequent assessment required by the study
-
Patient had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or had a clinically significant allergy to drugs, foods, amide local anaesthetics or other materials including commercial artificial tears (in the opinion of the investigator)
-
Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions:
-
are currently pregnant or,
-
have a positive result at the urine pregnancy test (Baseline/Day 0) or,
-
intend to become pregnant during the study treatment period or,
-
are breast-feeding or,
-
are not willing to use highly effective birth control measures, such as: hormonal contraceptives - oral, implanted, transdermal, or injected - and/or mechanical barrier methods - spermicide in conjunction with a barrier such as a condom or diaphragm or Intra Uterine Device (IUD) - during the entire course of and 30 days after the study treatment periods
-
Any concurrent medical condition, that in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient's well-being
-
Use of topical cyclosporine, topical corticosteroids or any other topical drug for the treatment of dry eye in either eye within 30 days of study enrolment.
-
Contact lenses or punctum plug use during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)
-
History of drug addiction or alcohol abuse
-
Any prior ocular surgery (including refractive palpebral and cataract surgery) if within 90 days before the screening visit
-
Participation in a clinical trial with a new active substance during the past 6 months
-
Participation in another clinical trial study at the same time as the present study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Global Research Management | Glendale | California | United States | 91204 |
2 | Eye Research Foundation | Newport Beach | California | United States | 92663 |
3 | Martel Eye Medical Group | Rancho Cordova | California | United States | 95670 |
4 | Sierra Clinical Trials & Research Organization | Santa Ana | California | United States | 92647 |
5 | Clayton Eye Clinical Research, LLC | Morrow | Georgia | United States | 30260 |
6 | Kentucky Eye Institute | Lexington | Kentucky | United States | 40517 |
7 | Tauber Eye Center | Kansas City | Missouri | United States | 64111 |
8 | Moyes Eye Center | Kansas City | Missouri | United States | 64154 |
9 | SightMD | Babylon | New York | United States | 11702 |
10 | Toyos Clinic | Nashville | Tennessee | United States | 37027 |
11 | Houston Eye Associates HEA - Gramercy Location | Houston | Texas | United States | 77025 |
12 | Advanced Laser Vision Surgical Institute (Study Site) Intouch Clinical Research Center (SMO) | Houston | Texas | United States | 77034 |
Sponsors and Collaborators
- Dompé Farmaceutici S.p.A
Investigators
- Study Director: Flavio Mantelli, MD, Dompé Farmaceutici SpA
- Principal Investigator: William Lipsky, MD, Advanced Laser Vision Surgical Institute (Study Site) Intouch Clinical Research Center (SMO)
Study Documents (Full-Text)
More Information
Publications
None provided.- NGF0118
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 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. |
Arm/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Period Title: Overall Study | |||
STARTED | 87 | 86 | 88 |
FAS Popuation | 81 | 82 | 84 |
PP Population | 72 | 71 | 80 |
COMPLETED | 74 | 79 | 83 |
NOT COMPLETED | 13 | 7 | 5 |
Baseline Characteristics
Arm/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID | Total |
---|---|---|---|---|
Arm/Group Description | 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) | 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. | 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) | Total of all reporting groups |
Overall Participants | 81 | 82 | 84 | 247 |
Age (Count of Participants) | ||||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
51
63%
|
54
65.9%
|
61
72.6%
|
166
67.2%
|
>=65 years |
30
37%
|
28
34.1%
|
23
27.4%
|
81
32.8%
|
Age (years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [years] |
62.0
(13.52)
|
60.2
(12.39)
|
59.1
(11.50)
|
60.4
(12.49)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
57
70.4%
|
69
84.1%
|
72
85.7%
|
198
80.2%
|
Male |
24
29.6%
|
13
15.9%
|
12
14.3%
|
49
19.8%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
15
18.5%
|
9
11%
|
13
15.5%
|
37
15%
|
Not Hispanic or Latino |
66
81.5%
|
73
89%
|
71
84.5%
|
210
85%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | ||||
United States |
81
100%
|
82
100%
|
84
100%
|
247
100%
|
Outcome Measures
Title | Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set |
---|---|
Description | The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes) Cutoff values: <5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
Least Squares Mean (Standard Error) [mm] |
2.60
(0.77)
|
3.99
(0.76)
|
1.68
(0.75)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.078 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | least square mean difference |
Estimated Value | 0.93 | |
Confidence Interval |
(2-Sided) 95% -1.47 to 3.32 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.066 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | least square mean difference |
Estimated Value | 2.31 | |
Confidence Interval |
(2-Sided) 95% -0.08 to 4.70 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Per Protocol Set |
---|---|
Description | The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes) Cutoff values: <5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
Least Squares Mean (Standard Error) [mm] |
2.99
(0.78)
|
3.72
(0.79)
|
1.28
(0.74)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.032 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 1.71 | |
Confidence Interval |
(2-Sided) 95% -0.70 to 4.12 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.029 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 2.44 | |
Confidence Interval |
(2-Sided) 95% 0.02 to 4.86 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Full Analysis Set |
---|---|
Description | The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The global score is calculated by taking the square root of the product of the severity of symptoms per the frequency of symptoms. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms. |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
Mean (Standard Deviation) [score on a scale] |
-24.6
(27.15)
|
-20.3
(24.91)
|
-22.2
(22.29)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.534 |
Comments | ||
Method | t-test, 2 sided | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.611 |
Comments | ||
Method | t-test, 2 sided | |
Comments |
Title | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Per Protocol Set |
---|---|
Description | The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The global score is calculated by taking the square root of the product of the severity of symptoms per the frequency of symptoms. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms. |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
Mean (Standard Deviation) [score on a scale] |
-24.9
(27.35)
|
-19.9
(25.34)
|
-22.1
(21.74)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.486 |
Comments | ||
Method | t-test, 2 sided | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.564 |
Comments | ||
Method | t-test, 2 sided | |
Comments |
Title | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Full Analysis Set |
---|---|
Description | The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome.The SANDE global score is calculated by taking the square root of the product of the frequency of symptoms and the severity of symptoms. The SANDE scale ranges from 0 to 100 wi.100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
Mean (Standard Deviation) [score on a scale] |
-24.9
(26.29)
|
-22.7
(25.42)
|
-24.0
(23.81)
|
Title | Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Per Protocol Set |
---|---|
Description | The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score. The SANDE scale ranges from 0 to 100 wi.100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms. |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
Mean (Standard Deviation) [score on a scale] |
-24.7
(26.73)
|
-22.2
(25.67)
|
-23.8
(23.92)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.810 |
Comments | ||
Method | t-test, 2 sided | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.733 |
Comments | ||
Method | t-test, 2 sided | |
Comments |
Title | Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Full Analysis Set |
---|---|
Description | The Schirmer II test is performed as the Schirmer I test after instilling anesthetic drops. The Schirmer strips are inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. All patients are seated at rest with their eyes closed, and the lower cul-de-sac is gently dried with a cotton applicator before the placement of strips. Cut-off values: <5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
Least Squares Mean (Standard Error) [mm] |
2.19
(0.69)
|
0.89
(0.69)
|
0.21
(0.68)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.025 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 1.97 | |
Confidence Interval |
(2-Sided) 95% -0.19 to 4.13 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.243 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 0.68 | |
Confidence Interval |
(2-Sided) 95% -1.48 to 2.83 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Per Protocol Set |
---|---|
Description | The Schirmer II test is performed as the Schirmer I test after instilling anesthetic drops. The Schirmer strips are inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. All patients are seated at rest with their eyes closed, and the lower cul-de-sac is gently dried with a cotton applicator before the placement of strips. Cut-off values: <5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
Least Squares Mean (Standard Error) [mm] |
2.24
(0.69)
|
0.54
(0.70)
|
-0.18
(0.66)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.007 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 2.41 | |
Confidence Interval |
(2-Sided) 95% 0.28 to 4.54 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.230 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 0.71 | |
Confidence Interval |
(2-Sided) 95% -1.43 to 2.85 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set |
---|---|
Description | Corneal staining total score is defined as the sum of scores from 5 corneal areas: Central, Superior, Temporal, Nasal, and Inferior. The score for each area ranges from 0 to 3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage. Thus, the corneal staining total score can range from 0 to 15 where the higher the score the worse is the outcome. The conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage and with a maximal score of 9 for the nasal and temporal conjunctiva. Thus, the conjunctival staining total score can range from 0 to 18 where the higher the score the worse is the outcome. Corneal and conjunctiva vital staining total score is the sum of corneal staining total score and conjunctiva total score. |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
corneal and conjunctival total score |
-3.75
(0.63)
|
-2.95
(0.62)
|
-2.60
(0.61)
|
corneal score |
-1.9
(2.84)
|
-1.8
(2.72)
|
-1.5
(2.92)
|
conjunctiva score |
-2.1
(3.17)
|
-1.2
(3.58)
|
-1.4
(3.36)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.799 |
Comments | ||
Method | ANOVA | |
Comments | Last Observation Carried Forward (LOCF) was used for imputing missing data in the Full analysis set at Week 4. | |
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -1.16 | |
Confidence Interval |
(2-Sided) 95% -3.11 to 0.80 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.715 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -0.36 | |
Confidence Interval |
(2-Sided) 95% -2.30 to 1.59 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set |
---|---|
Description | Corneal staining total score is defined as the sum of scores from 5 corneal areas: Central, Superior, Temporal, Nasal, and Inferior. The score for each area ranges from 0 to 3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage. Thus, the corneal staining total score can range from 0 to 15 where the higher the score the worse is the outcome. The conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage and with a maximal score of 9 for the nasal and temporal conjunctiva. Thus, the conjunctival staining total score can range from 0 to 18 where the higher the score the worse is the outcome. Corneal and conjunctiva vital staining total score is the sum of corneal staining total score and conjunctiva total score. |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
Total score |
-3.94
(0.60)
|
-2.61
(0.61)
|
-2.40
(0.57)
|
Corneal score |
-1.9
(2.80)
|
-1.8
(2.61)
|
-1.5
(2.85)
|
Conjunctival score |
-1.9
(2.95)
|
-1.0
(3.05)
|
-1.3
(3.32)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.831 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -1.54 | |
Confidence Interval |
(2-Sided) 95% -3.40 to 0.31 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.750 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -0.21 | |
Confidence Interval |
(2-Sided) 95% -2.07 to 1.66 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Full Analysis Set |
---|---|
Description | Tear film break-up time (TFBUT) is the time taken to appear first dry spot on cornea after a complete blinking. TFBUT measurement is an easy and fast method used to assess the stability of tear film. It is a standard diagnostic procedure in the dry eye clinics. TFBUT is measured by determining the time to tear break-up. The TFBUT is performed after instillation of 5 μL of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient is instructed to blink several times to thoroughly mix the fluorescein with the tear film. A TFBUT greater than 15 seconds is considered normal, while a break time of less than 10 seconds is to be considered pathological. |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
Least Squares Mean (Standard Error) [seconds] |
1.11
(0.25)
|
0.43
(0.25)
|
0.15
(0.25)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.004 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 95% 0.17 to 1.75 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.217 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 0.28 | |
Confidence Interval |
(2-Sided) 95% -0.51 to 1.07 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Per Protocol Set |
---|---|
Description | Tear film break-up time (TFBUT) is the time taken to appear first dry spot on cornea after a complete blinking. TFBUT measurement is an easy and fast method used to assess the stability of tear film. It is a standard diagnostic procedure in the dry eye clinics. TFBUT is measured by determining the time to tear break-up. The TFBUT is performed after instillation of 5 μL of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient is instructed to blink several times to thoroughly mix the fluorescein with the tear film. A TFBUT greater than 15 seconds is considered normal, while a break time of less than 10 seconds is to be considered pathological. |
Time Frame | Baseline, week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
Least Squares Mean (Standard Error) [seconds] |
1.11
(0.27)
|
0.47
(0.27)
|
0.19
(0.25)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.007 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 0.92 | |
Confidence Interval |
(2-Sided) 95% 0.10 to 1.74 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.225 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 0.28 | |
Confidence Interval |
(2-Sided) 95% -0.54 to 1.10 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Full Analysis Set |
---|---|
Description | The SANDE score is calculated by taking the square root of the product of the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms. The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage. The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15. Both nasally and temporally, the conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (overall the total score ranged from 0-18). Briefly, grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector. |
Time Frame | At week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
Count of Participants [Participants] |
2
2.5%
|
9
11%
|
3
3.6%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.680 |
Comments | ||
Method | t-test, 2 sided | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.066 |
Comments | ||
Method | t-test, 2 sided | |
Comments |
Title | Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Per Protocol Set |
---|---|
Description | The SANDE score is calculated by taking the square root of the product of the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms. The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage. The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15. Both nasally and temporally, the conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (overall the total score ranged from 0-18). Briefly, grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector. |
Time Frame | At week 4 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
Count of Participants [Participants] |
0
0%
|
8
9.8%
|
3
3.6%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.097 |
Comments | ||
Method | Chi-squared | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.076 |
Comments | ||
Method | Chi-squared | |
Comments |
Title | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set |
---|---|
Description | IDEEL assesses quality of life, symptoms and treatment effects on patients with dry eye. The IDEEL contains 3 modules (Daily Activities, Treatment Satisfaction, and Symptom Bother) with a total of 57 questions. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops. The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother. Scores for each dimensions ranged from 0 to 100. Higher scores for: dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities; symptom-bother dimension indicates greater bother due to symptoms; satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness; treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience. |
Time Frame | At weeks 4, 8, 12 and 16 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
Daily activity limitations - Chance from baseline to week 4 |
16.5
(20.71)
|
19.5
(17.55)
|
13.1
(20.60)
|
Daily activity limitations - Chance from baseline to week 8 |
16.8
(23.49)
|
14.8
(18.07)
|
11.2
(17.54)
|
Daily activity limitations - Chance from baseline to week 12 |
15.7
(21.10)
|
15.5
(20.01)
|
11.1
(17.45)
|
Daily activity limitations - Chance from baseline to week 16 |
14.2
(20.05)
|
14.4
(21.23)
|
9.4
(16.74)
|
Emotional well-being - change from baseline to week 4 |
14.5
(21.18)
|
16.3
(20.40)
|
15.0
(20.47)
|
Emotional well-being - change from baseline to week 8 |
16.2
(21.33)
|
13.4
(18.64)
|
12.7
(17.69)
|
Emotional well-being - change from baseline to week 12 |
14.2
(18.66)
|
15.3
(17.95)
|
14.2
(18.20)
|
Emotional well-being - change from baseline to week 16 |
16.0
(18.54)
|
15.5
(19.17)
|
13.5
(20.22)
|
work limitations - change from baseline to week 4 |
16.3
(27.13)
|
20.6
(24.29)
|
17.4
(24.09)
|
work limitations - change from baseline to week 8 |
18.0
(24.94)
|
18.3
(19.00)
|
17.0
(22.52)
|
work limitations - change from baseline to week 12 |
16.4
(22.39)
|
20.9
(22.05)
|
17.8
(22.35)
|
work limitations - change from baseline to week 16 |
16.3
(20.75)
|
20.9
(20.83)
|
16.0
(21.63)
|
Treatment satisfaction/happiness - change from baseline to week 4 |
24.1
(30.81)
|
19.0
(30.57)
|
24.1
(33.57)
|
Treatment satisfaction/happiness - change from baseline to week 8 |
28.8
(28.56)
|
19.1
(26.90)
|
13.3
(30.69)
|
Treatment satisfaction/happiness - change from baseline to week 12 |
26.1
(30.30)
|
19.1
(27.86)
|
15.0
(26.83)
|
Treatment satisfaction/happiness - change from baseline to week 16 |
26.1
(26.62)
|
23.5
(29.29)
|
12.7
(27.03)
|
treatment-related bother - change from baseline to week 4 |
14.6
(22.78)
|
16.8
(25.00)
|
13.8
(27.19)
|
treatment-related bother - change from baseline to week 8 |
10.6
(20.61)
|
6.5
(26.56)
|
4.8
(26.59)
|
treatment-related bother - change from baseline to week 12 |
10.3
(22.71)
|
8.7
(24.91)
|
9.0
(27.95)
|
treatment-related bother - change from baseline to week 16 |
10.8
(20.65)
|
8.1
(23.88)
|
10.0
(27.14)
|
Dry eye symptom bother - change from baseline to week 4 |
-16.8
(17.80)
|
-17.7
(16.54)
|
-16.5
(17.04)
|
Dry eye symptom bother - change from baseline to week 8 |
-21.2
(19.56)
|
-16.6
(15.46)
|
-13.5
(15.01)
|
Dry eye symptom bother - change from baseline to week 12 |
-19.6
(17.41)
|
-18.2
(17.30)
|
-13.0
(13.01)
|
Dry eye symptom bother - change from baseline to week 16 |
-19.9
(15.62)
|
-19.1
(17.75)
|
-11.1
(14.46)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.289 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.4 | |
Confidence Interval |
(2-Sided) 95% 12.0 to 20.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.032 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 19.7 | |
Confidence Interval |
(2-Sided) 95% 15.4 to 24.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change to baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.095 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.4 | |
Confidence Interval |
(2-Sided) 95% 11.9 to 20.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.282 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 14.5 | |
Confidence Interval |
(2-Sided) 95% 10.1 to 18.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.169 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.0 | |
Confidence Interval |
(2-Sided) 95% 10.6 to 19.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.129 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.4 | |
Confidence Interval |
(2-Sided) 95% 11.1 to 19.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.111 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 14.0 | |
Confidence Interval |
(2-Sided) 95% 9.7 to 18.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.107 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 14.0 | |
Confidence Interval |
(2-Sided) 95% 9.7 to 18.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 9
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.827 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 14.3 | |
Confidence Interval |
(2-Sided) 95% 9.7 to 18.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 10
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.688 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.3 | |
Confidence Interval |
(2-Sided) 95% 11.8 to 20.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 11
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.324 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.7 | |
Confidence Interval |
(2-Sided) 95% 11.4 to 20.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 12
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.949 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 12.9 | |
Confidence Interval |
(2-Sided) 95% 8.7 to 17.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 13
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.927 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.7 | |
Confidence Interval |
(2-Sided) 95% 11.4 to 20.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 14
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.776 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 14.8 | |
Confidence Interval |
(2-Sided) 95% 10.8 to 18.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 15
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.418 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.7 | |
Confidence Interval |
(2-Sided) 95% 11.4 to 20.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 16
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.613 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 14.8 | |
Confidence Interval |
(2-Sided) 95% 10.6 to 19.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 17
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.721 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.8 | |
Confidence Interval |
(2-Sided) 95% 8.3 to 23.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 18
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.558 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 20.6 | |
Confidence Interval |
(2-Sided) 95% 13.1 to 28.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 19
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.809 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 18.4 | |
Confidence Interval |
(2-Sided) 95% 11.5 to 25.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 20
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.651 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 19.4 | |
Confidence Interval |
(2-Sided) 95% 12.4 to 26.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 21
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.769 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.4 | |
Confidence Interval |
(2-Sided) 95% 9.5 to 23.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 22
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.454 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 21.3 | |
Confidence Interval |
(2-Sided) 95% 14.3 to 28.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 23
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.564 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 18.3 | |
Confidence Interval |
(2-Sided) 95% 11.6 to 25.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 24
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.250 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 21.0 | |
Confidence Interval |
(2-Sided) 95% 14.1 to 27.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 25
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.853 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 23.9 | |
Confidence Interval |
(2-Sided) 95% 15.6 to 32.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 26
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.393 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 20.0 | |
Confidence Interval |
(2-Sided) 95% 11.9 to 28.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 27
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.010 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 27.9 | |
Confidence Interval |
(2-Sided) 95% 20.2 to 35.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 28
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.395 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 18.3 | |
Confidence Interval |
(2-Sided) 95% 11.1 to 25.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 29
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.068 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 24.8 | |
Confidence Interval |
(2-Sided) 95% 17.1 to 32.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 30
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.400 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 19.3 | |
Confidence Interval |
(2-Sided) 95% 12.2 to 26.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 31
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.021 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 25.5 | |
Confidence Interval |
(2-Sided) 95% 18.1 to 33.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 32
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.056 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 23.1 | |
Confidence Interval |
(2-Sided) 95% 16.1 to 30.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 33
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.981 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 14.2 | |
Confidence Interval |
(2-Sided) 95% 7.6 to 20.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 34
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.525 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 17.0 | |
Confidence Interval |
(2-Sided) 95% 11.1 to 22.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 35
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.356 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 9.5 | |
Confidence Interval |
(2-Sided) 95% 2.9 to 16.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 36
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.771 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 6.5 | |
Confidence Interval |
(2-Sided) 95% 0.7 to 12.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 37
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.926 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 8.7 | |
Confidence Interval |
(2-Sided) 95% 2.0 to 15.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 38
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.778 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 7.9 | |
Confidence Interval |
(2-Sided) 95% 1.9 to 13.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 39
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.984 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 10.0 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 40
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.514 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 7.4 | |
Confidence Interval |
(2-Sided) 95% 1.6 to 13.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 41
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.985 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -16.6 | |
Confidence Interval |
(2-Sided) 95% -20.4 to -12.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 42
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.646 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -17.8 | |
Confidence Interval |
(2-Sided) 95% -21.5 to -14.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 43
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.007 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -20.7 | |
Confidence Interval |
(2-Sided) 95% -24.5 to -16.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 44
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.305 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -16.2 | |
Confidence Interval |
(2-Sided) 95% -19.9 to -12.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 45
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.015 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -19.0 | |
Confidence Interval |
(2-Sided) 95% -22.7 to -15.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 46
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.039 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -18.0 | |
Confidence Interval |
(2-Sided) 95% -21.5 to -14.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 47
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.001 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -19.7 | |
Confidence Interval |
(2-Sided) 95% -23.3 to -16.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 48
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.002 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -18.9 | |
Confidence Interval |
(2-Sided) 95% -22.4 to -15.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set |
---|---|
Description | IDEEL assesses quality of life, symptoms and treatment effects on patients with dry eye. The IDEEL contains 3 modules (Daily Activities, Treatment Satisfaction, and Symptom Bother) with a total of 57 questions. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops. The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother. Scores for each dimensions ranged from 0 to 100. Higher scores for: dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities; symptom-bother dimension indicates greater bother due to symptoms; satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness; treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience. |
Time Frame | At weeks 4, 8, 12 and 16 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
Daily activity limitations - Change from baseline to week 4 |
16.8
(21.20)
|
19.7
(17.58)
|
13.0
(20.63)
|
Daily activity limitations - Change from baseline to week 8 |
17.1
(23.93)
|
15.3
(16.85)
|
11.5
(17.47)
|
Daily activity limitations - Change from baseline to week 12 |
17.0
(20.30)
|
16.5
(18.45)
|
11.2
(17.64)
|
Daily activity limitations - Change from baseline to week 16 |
13.9
(19.33)
|
15.8
(19.74)
|
9.4
(16.94)
|
Emotional well-being - change from baseline to week 4 |
15.2
(21.73)
|
17.3
(20.33)
|
15.8
(20.60)
|
Emotional well-being - change from baseline to week 8 |
16.9
(21.70)
|
13.9
(18.34)
|
13.2
(17.55)
|
Emotional well-being - change from baseline to week 12 |
15.1
(18.58)
|
16.4
(16.87)
|
14.7
(18.14)
|
Emotional well-being - change from baseline to week 16 |
16.8
(18.48)
|
16.6
(18.59)
|
14.2
(20.11)
|
work limitations - change from baseline to week 4 |
16.0
(27.48)
|
21.3
(24.83)
|
18.4
(24.23)
|
work limitations - change from baseline to week 8 |
17.4
(25.13)
|
18.3
(19.43)
|
17.9
(22.29)
|
work limitations - change from baseline to week 12 |
15.0
(21.67)
|
21.9
(21.82)
|
18.6
(22.14)
|
work limitations - change from baseline to week 16 |
15.4
(19.43)
|
21.9
(20.93)
|
16.7
(21.80)
|
Treatment satisfaction/happiness - change from baseline to week 4 |
25.4
(31.05)
|
19.6
(31.26)
|
25.2
(33.81)
|
Treatment satisfaction/happiness - change from baseline to week 8 |
30.1
(28.47)
|
21.0
(27.85)
|
13.9
(30.66)
|
Treatment satisfaction/happiness - change from baseline to week 12 |
25.8
(31.16)
|
21.6
(27.82)
|
15.5
(26.81)
|
Treatment satisfaction/happiness - change from baseline to week 16 |
26.0
(27.60)
|
24.3
(28.26)
|
13.2
(27.18)
|
treatment-related bother - change from baseline to week 4 |
15.7
(22.66)
|
15.3
(23.39)
|
14.4
(27.71)
|
treatment-related bother - change from baseline to week 8 |
11.6
(20.73)
|
6.9
(25.46)
|
4.6
(26.78)
|
treatment-related bother - change from baseline to week 12 |
9.9
(22.83)
|
10.0
(23.05)
|
8.7
(28.26)
|
treatment-related bother - change from baseline to week 16 |
11.4
(20.90)
|
9.5
(21.62)
|
9.8
(27.51)
|
Dry eye symptom bother - change from baseline to week 4 |
-17.3
(17.19)
|
-18.7
(16.64)
|
-17.2
(17.10)
|
Dry eye symptom bother - change from baseline to week 8 |
-21.5
(18.88)
|
-17.6
(15.40)
|
-13.9
(14.97)
|
Dry eye symptom bother - change from baseline to week 12 |
-19.6
(17.41)
|
-19.7
(17.16)
|
-13.2
(13.18)
|
Dry eye symptom bother - change from baseline to week 16 |
-20.6
(15.21)
|
-20.7
(17.66)
|
-11.3
(14.61)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.241 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.8 | |
Confidence Interval |
(2-Sided) 95% 12.2 to 21.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.040 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 19.7 | |
Confidence Interval |
(2-Sided) 95% 15.1 to 24.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.097 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.8 | |
Confidence Interval |
(2-Sided) 95% 12.3 to 21.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.238 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.3 | |
Confidence Interval |
(2-Sided) 95% 10.7 to 19.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.070 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.5 | |
Confidence Interval |
(2-Sided) 95% 12.0 to 20.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.058 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.7 | |
Confidence Interval |
(2-Sided) 95% 12.3 to 21.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.128 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 13.7 | |
Confidence Interval |
(2-Sided) 95% 9.3 to 18.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Daily Activity Limitations - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.024 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.0 | |
Confidence Interval |
(2-Sided) 95% 11.6 to 20.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 9
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.865 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.2 | |
Confidence Interval |
(2-Sided) 95% 10.4 to 20.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 10
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.662 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 17.3 | |
Confidence Interval |
(2-Sided) 95% 12.4 to 22.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 11
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.266 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.7 | |
Confidence Interval |
(2-Sided) 95% 12.2 to 21.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 12
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.824 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 13.9 | |
Confidence Interval |
(2-Sided) 95% 9.4 to 18.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 13
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.883 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 14.8 | |
Confidence Interval |
(2-Sided) 95% 10.6 to 19.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 14
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.516 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.3 | |
Confidence Interval |
(2-Sided) 95% 12.1 to 20.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 15
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | Emotional Well-Being - change from baseline to week 16 | |
Statistical Test of Hypothesis | p-Value | 0.407 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.5 | |
Confidence Interval |
(2-Sided) 95% 12.1 to 21.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 16
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Emotional Well-Being - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.422 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 16.4 | |
Confidence Interval |
(2-Sided) 95% 12.0 to 20.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 17
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Work Limitations - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.615 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.9 | |
Confidence Interval |
(2-Sided) 95% 8.1 to 23.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 18
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.626 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 21.3 | |
Confidence Interval |
(2-Sided) 95% 13.3 to 29.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 19
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Work Limitations - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.968 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 18.3 | |
Confidence Interval |
(2-Sided) 95% 11.1 to 25.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 20
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.689 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 20.1 | |
Confidence Interval |
(2-Sided) 95% 12.8 to 27.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 21
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Work Limitations - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.528 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.6 | |
Confidence Interval |
(2-Sided) 95% 8.5 to 22.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 22
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.368 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 23.0 | |
Confidence Interval |
(2-Sided) 95% 15.8 to 30.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 23
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Work Limitations - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.764 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 17.7 | |
Confidence Interval |
(2-Sided) 95% 10.7 to 24.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 24
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Work Limitations - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.184 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 22.6 | |
Confidence Interval |
(2-Sided) 95% 15.5 to 29.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 25
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.909 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 25.4 | |
Confidence Interval |
(2-Sided) 95% 16.5 to 34.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 26
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.428 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 21.1 | |
Confidence Interval |
(2-Sided) 95% 12.2 to 30.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 27
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.008 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 29.8 | |
Confidence Interval |
(2-Sided) 95% 21.6 to 37.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 28
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.222 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 21.3 | |
Confidence Interval |
(2-Sided) 95% 13.5 to 29.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 29
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.082 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 25.3 | |
Confidence Interval |
(2-Sided) 95% 17.2 to 33.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 30
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.154 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 23.3 | |
Confidence Interval |
(2-Sided) 95% 15.6 to 31.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 31
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.030 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 25.8 | |
Confidence Interval |
(2-Sided) 95% 18.0 to 33.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 32
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment Satisfaction - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.046 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 24.6 | |
Confidence Interval |
(2-Sided) 95% 17.1 to 32.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 33
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.861 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.4 | |
Confidence Interval |
(2-Sided) 95% 8.6 to 22.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 34
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.865 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 15.3 | |
Confidence Interval |
(2-Sided) 95% 9.0 to 21.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 35
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.278 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 10.5 | |
Confidence Interval |
(2-Sided) 95% 3.6 to 17.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 36
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.689 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 7.2 | |
Confidence Interval |
(2-Sided) 95% 0.9 to 13.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 37
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.993 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 9.1 | |
Confidence Interval |
(2-Sided) 95% 2.1 to 16.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 38
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.989 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 9.2 | |
Confidence Interval |
(2-Sided) 95% 2.8 to 15.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 39
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.976 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 10.4 | |
Confidence Interval |
(2-Sided) 95% 3.7 to 17.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 40
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Treatment-Related Bother - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.778 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 9.0 | |
Confidence Interval |
(2-Sided) 95% 2.9 to 15.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 41
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Symptom Bother - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.964 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -17.3 | |
Confidence Interval |
(2-Sided) 95% -21.2 to -13.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 42
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.581 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -18.7 | |
Confidence Interval |
(2-Sided) 95% -22.7 to -14.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 43
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Symptom Bother - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.006 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -21.4 | |
Confidence Interval |
(2-Sided) 95% -25.2 to -17.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 44
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.175 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -17.6 | |
Confidence Interval |
(2-Sided) 95% -21.4 to -13.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 45
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Symptom Bother - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.016 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -19.4 | |
Confidence Interval |
(2-Sided) 95% -23.1 to -15.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 46
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.010 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -19.8 | |
Confidence Interval |
(2-Sided) 95% -23.5 to -16.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 47
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | Symptom Bother - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.000 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -20.5 | |
Confidence Interval |
(2-Sided) 95% -24.3 to -16.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 48
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | Symptom Bother - change from baseline to week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.000 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | -20.8 | |
Confidence Interval |
(2-Sided) 95% -24.6 to -17.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Patient Global Impression of Change (PGIC) - Full Analysis Set |
---|---|
Description | PGIC is a commonly used method of assessing clinically important change. With PGIC the qualitative assessment of meaningful change is determined by the patient on 7-items using a 0 (very much improved) to 10 (very much worse) scale. |
Time Frame | At baseline and weeks 4, 8, 12 and 16 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
week 4 - Very Much Improved |
11
13.6%
|
2
2.4%
|
4
4.8%
|
week 4 - Much Improved |
18
22.2%
|
15
18.3%
|
20
23.8%
|
week 4 - Minimally improved |
18
22.2%
|
21
25.6%
|
20
23.8%
|
week 4 - no change |
24
29.6%
|
38
46.3%
|
38
45.2%
|
week 4 - minimally worse |
6
7.4%
|
4
4.9%
|
2
2.4%
|
week 4 - much worse |
1
1.2%
|
1
1.2%
|
0
0%
|
week 4 - very much worse |
0
0%
|
0
0%
|
0
0%
|
week 8 - Very much improved |
9
11.1%
|
3
3.7%
|
1
1.2%
|
week 8 - much improved |
23
28.4%
|
11
13.4%
|
16
19%
|
week 8 - minimally improved |
19
23.5%
|
21
25.6%
|
17
20.2%
|
week 8 - no change |
21
25.9%
|
37
45.1%
|
46
54.8%
|
week 8 - minimally worse |
1
1.2%
|
4
4.9%
|
2
2.4%
|
week 8 - much worse |
0
0%
|
1
1.2%
|
2
2.4%
|
week 8 - very much worse |
1
1.2%
|
1
1.2%
|
0
0%
|
week 12 - very much improved |
11
13.6%
|
3
3.7%
|
4
4.8%
|
week 12 - much improved |
16
19.8%
|
10
12.2%
|
12
14.3%
|
week 12 - minimally improved |
22
27.2%
|
24
29.3%
|
24
28.6%
|
week 12 - no change |
15
18.5%
|
36
43.9%
|
40
47.6%
|
week 12 - minimally worse |
5
6.2%
|
1
1.2%
|
0
0%
|
week 12 - much worse |
2
2.5%
|
2
2.4%
|
2
2.4%
|
week 12 - very much worse |
2
2.5%
|
1
1.2%
|
0
0%
|
week 16 - very much improved |
7
8.6%
|
3
3.7%
|
6
7.1%
|
week 16 - much improved |
24
29.6%
|
19
23.2%
|
16
19%
|
week 16 - minimally improved |
22
27.2%
|
20
24.4%
|
19
22.6%
|
week 16 - no change |
19
23.5%
|
33
40.2%
|
36
42.9%
|
week 16 - minimally worse |
2
2.5%
|
2
2.4%
|
5
6%
|
week 16 - much worse |
1
1.2%
|
0
0%
|
0
0%
|
week 16 - very much worse |
0
0%
|
1
1.2%
|
0
0%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | at week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.302 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | at week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.224 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | at week 8 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.000 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | at week 8 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.885 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | At week 12 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.035 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | At week 12 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.698 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | At week 16 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.016 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | At week 16 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.706 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Title | Patient Global Impression of Change (PGIC) - Per Protocol Set |
---|---|
Description | PGIC is a commonly used method of assessing clinically important change. With PGIC the qualitative assessment of meaningful change is determined by the patient on 7-items using a 0 (very much improved) to 10 (very much worse) scale. |
Time Frame | At weeks 4, 8, 12 and 16 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
week 4 - Very Much Improved |
10
12.3%
|
2
2.4%
|
4
4.8%
|
week 4 - Much Improved |
18
22.2%
|
12
14.6%
|
18
21.4%
|
week 4 - Minimally improved |
17
21%
|
19
23.2%
|
20
23.8%
|
week 4 - no change |
20
24.7%
|
34
41.5%
|
36
42.9%
|
week 4 - minimally worse |
6
7.4%
|
4
4.9%
|
2
2.4%
|
week 4 - much worse |
1
1.2%
|
0
0%
|
0
0%
|
week 4 - very much worse |
0
0%
|
0
0%
|
0
0%
|
week 8 - Very much improved |
9
11.1%
|
3
3.7%
|
1
1.2%
|
week 8 - much improved |
21
25.9%
|
9
11%
|
15
17.9%
|
week 8 - minimally improved |
18
22.2%
|
21
25.6%
|
17
20.2%
|
week 8 - no change |
20
24.7%
|
34
41.5%
|
43
51.2%
|
week 8 - minimally worse |
1
1.2%
|
3
3.7%
|
2
2.4%
|
week 8 - much worse |
0
0%
|
1
1.2%
|
2
2.4%
|
week 8 - very much worse |
0
0%
|
0
0%
|
0
0%
|
week 12 - very much improved |
11
13.6%
|
3
3.7%
|
4
4.8%
|
week 12 - much improved |
13
16%
|
9
11%
|
11
13.1%
|
week 12 - minimally improved |
21
25.9%
|
23
28%
|
23
27.4%
|
week 12 - no change |
15
18.5%
|
33
40.2%
|
38
45.2%
|
week 12 - minimally worse |
5
6.2%
|
1
1.2%
|
0
0%
|
week 12 - much worse |
2
2.5%
|
1
1.2%
|
2
2.4%
|
week 12 - very much worse |
1
1.2%
|
0
0%
|
0
0%
|
week 16 - very much improved |
7
8.6%
|
3
3.7%
|
6
7.1%
|
week 16 - much improved |
22
27.2%
|
18
22%
|
15
17.9%
|
week 16 - minimally improved |
19
23.5%
|
17
20.7%
|
18
21.4%
|
week 16 - no change |
19
23.5%
|
30
36.6%
|
34
40.5%
|
week 16 - minimally worse |
2
2.5%
|
2
2.4%
|
5
6%
|
week 16 - much worse |
0
0%
|
0
0%
|
0
0%
|
week 16 - very much worse |
0
0%
|
0
0%
|
0
0%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | at week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.210 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | at weeek 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.260 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | At week 8 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.000 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | at week 8 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.734 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | at week 12 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.050 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | at week 12 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.985 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | at week 16 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.018 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | at week 16 (FUP) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.580 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Title | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set |
---|---|
Description | EQ-5D is a standardised measure of health status. - The EQ-5D 3 level version (EQ-5D-3L) consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) which are summed up. The EQ-5D-3L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. This scale ranges from 5 (best case) to 15 (worst case). Each dimension has 3 levels: no problems, some problems, extreme problems (labelled 1-3). The respondent must indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions. - The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This is a quantitative measure of health outcome, judged by each respondent. Both for total and partial scores, the higher the score, the worse is the outcome. |
Time Frame | At weeks 4, 8, 12 and 16 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 81 | 82 | 84 |
week 4 |
1.2
(9.91)
|
3.8
(10.28)
|
2.8
(8.86)
|
week 8 |
2.7
(10.41)
|
2.4
(8.92)
|
2.1
(8.86)
|
week 12 |
3.0
(10.10)
|
3.0
(7.8)
|
3.0
(8.59)
|
week 16 |
3.0
(13.04)
|
4.8
(11.92)
|
2.0
(11.71)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.282 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 1.2 | |
Confidence Interval |
(2-Sided) 95% -1.0 to 3.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.497 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 3.9 | |
Confidence Interval |
(2-Sided) 95% 1.7 to 6.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.734 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 2.6 | |
Confidence Interval |
(2-Sided) 95% 0.5 to 4.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.963 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 2.2 | |
Confidence Interval |
(2-Sided) 95% 0.1 to 4.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.854 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 2.7 | |
Confidence Interval |
(2-Sided) 95% 0.7 to 4.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.881 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 2.8 | |
Confidence Interval |
(2-Sided) 95% 0.8 to 4.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.632 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 3.0 | |
Confidence Interval |
(2-Sided) 95% 0.3 to 5.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.220 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 4.4 | |
Confidence Interval |
(2-Sided) 95% 1.7 to 7.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set |
---|---|
Description | EQ-5D is a standardised measure of health status. - The EQ-5D 3 level version (EQ-5D-3L) consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) which are summed up. The EQ-5D-3L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. This scale ranges from 5 (best case) to 15 (worst case). Each dimension has 3 levels: no problems, some problems, extreme problems (labelled 1-3). The respondent must indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions. - The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This is a quantitative measure of health outcome, judged by each respondent. Both for total and partial scores, the higher the score, the worse is the outcome. |
Time Frame | Aat baseline and weeks 4, 8, 12 and 16 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | rhNGF 20 μg/ml TID | rhNGF 20 μg/ml BID + Vehicle OD | Vehicle TID |
---|---|---|---|
Arm/Group Description | 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) | 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. | 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) |
Measure Participants | 72 | 71 | 80 |
week 4 |
1.2
(9.98)
|
3.6
(8.12)
|
2.8
(8.99)
|
week 8 |
2.7
(10.67)
|
2.3
(9.02)
|
2.2
(8.79)
|
week 12 |
3.6
(9.77)
|
3.4
(5.00)
|
3.0
(8.71)
|
week 16 |
3.3
(13.24)
|
4.7
(8.84)
|
1.9
(11.90)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.296 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 1.2 | |
Confidence Interval |
(2-Sided) 95% -0.9 to 3.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 4 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.570 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 3.6 | |
Confidence Interval |
(2-Sided) 95% 1.5 to 5.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | statistical analysis at week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.754 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 2.7 | |
Confidence Interval |
(2-Sided) 95% 0.5 to 4.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 8 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.972 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 2.3 | |
Confidence Interval |
(2-Sided) 95% 0.0 to 4.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, rhNGF 20 μg/ml BID + Vehicle OD |
---|---|---|
Comments | statistical analysis at week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.793 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 3.4 | |
Confidence Interval |
(2-Sided) 95% 1.4 to 5.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 12 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.766 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 3.4 | |
Confidence Interval |
(2-Sided) 95% 1.5 to 5.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml TID, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.458 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 3.3 | |
Confidence Interval |
(2-Sided) 95% 0.6 to 6.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | rhNGF 20 μg/ml BID + Vehicle OD, Vehicle TID |
---|---|---|
Comments | statistical analysis at week 16 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.147 |
Comments | ||
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square mean difference |
Estimated Value | 4.6 | |
Confidence Interval |
(2-Sided) 95% 2.0 to 7.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | From Screening day to week 16 | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112). | |||||||||||
Arm/Group Title | rhNGF 20 μg/ml TID - Treatment Period | rhNGF 20 μg/ml BID + Vehicle OD - Treatment Period | Vehicle TID - Treatment Period | rhNGF 20 μg/ml TID - Follow-up Period | rhNGF 20 μg/ml BID + Vehicle OD - Follow-up Period | Vehicle TID - Follow up Period | ||||||
Arm/Group Description | 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) | 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. | 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) | 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) | 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. | 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) | ||||||
All Cause Mortality |
||||||||||||
rhNGF 20 μg/ml TID - Treatment Period | rhNGF 20 μg/ml BID + Vehicle OD - Treatment Period | Vehicle TID - Treatment Period | rhNGF 20 μg/ml TID - Follow-up Period | rhNGF 20 μg/ml BID + Vehicle OD - Follow-up Period | Vehicle TID - Follow up Period | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/85 (0%) | 0/84 (0%) | 0/88 (0%) | 0/85 (0%) | 0/84 (0%) | 0/88 (0%) | ||||||
Serious Adverse Events |
||||||||||||
rhNGF 20 μg/ml TID - Treatment Period | rhNGF 20 μg/ml BID + Vehicle OD - Treatment Period | Vehicle TID - Treatment Period | rhNGF 20 μg/ml TID - Follow-up Period | rhNGF 20 μg/ml BID + Vehicle OD - Follow-up Period | Vehicle TID - Follow up Period | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/85 (0%) | 0/84 (0%) | 0/88 (0%) | 1/85 (1.2%) | 0/84 (0%) | 1/88 (1.1%) | ||||||
Cardiac disorders | ||||||||||||
Atrial fibrillation | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Injury, poisoning and procedural complications | ||||||||||||
Humerus fracture | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||
rhNGF 20 μg/ml TID - Treatment Period | rhNGF 20 μg/ml BID + Vehicle OD - Treatment Period | Vehicle TID - Treatment Period | rhNGF 20 μg/ml TID - Follow-up Period | rhNGF 20 μg/ml BID + Vehicle OD - Follow-up Period | Vehicle TID - Follow up Period | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 65/85 (76.5%) | 60/84 (71.4%) | 26/88 (29.5%) | 19/85 (22.4%) | 19/84 (22.6%) | 18/88 (20.5%) | ||||||
Ear and labyrinth disorders | ||||||||||||
Ear pain | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Eye disorders | ||||||||||||
Asthenopia | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Blepharitis | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Blepharospasm | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Chalazion | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 2/84 (2.4%) | 3 | 1/88 (1.1%) | 1 |
Conjunctival Disorder | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Conjunctival Haemorrhage | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Conjunctival Hyperaemia | 1/85 (1.2%) | 1 | 2/84 (2.4%) | 2 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Diplopia | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Dry Eye | 1/85 (1.2%) | 2 | 3/84 (3.6%) | 3 | 5/88 (5.7%) | 6 | 2/85 (2.4%) | 2 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Erythema Of Eyelid | 0/85 (0%) | 0 | 1/84 (1.2%) | 2 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 1/84 (1.2%) | 3 | 0/88 (0%) | 0 |
Eye Allergy | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Eye Discharge | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Eye Disorder | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Eye Irritation | 2/85 (2.4%) | 2 | 5/84 (6%) | 14 | 5/88 (5.7%) | 6 | 1/85 (1.2%) | 1 | 2/84 (2.4%) | 5 | 4/88 (4.5%) | 4 |
Eye Pain | 54/85 (63.5%) | 68 | 42/84 (50%) | 73 | 4/88 (4.5%) | 5 | 1/85 (1.2%) | 1 | 1/84 (1.2%) | 1 | 1/88 (1.1%) | 1 |
Eye Pruritus | 2/85 (2.4%) | 4 | 2/84 (2.4%) | 2 | 1/88 (1.1%) | 2 | 2/85 (2.4%) | 2 | 1/84 (1.2%) | 1 | 1/88 (1.1%) | 1 |
Eye Swelling | 1/85 (1.2%) | 1 | 2/84 (2.4%) | 2 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Eyelid Disorder | 1/85 (1.2%) | 4 | 3/84 (3.6%) | 3 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Eyelid Irritation | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Eyelid Oedema | 1/85 (1.2%) | 1 | 2/84 (2.4%) | 2 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Eyelid Pain | 3/85 (3.5%) | 6 | 9/84 (10.7%) | 15 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Foreign Body Sensation In Eyes | 1/85 (1.2%) | 1 | 3/84 (3.6%) | 3 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Lacrimation Increased | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Meibomian Gland Dysfunction | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 1/84 (1.2%) | 2 | 0/88 (0%) | 0 |
Ocular Discomfort | 6/85 (7.1%) | 9 | 4/84 (4.8%) | 4 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Ocular Hyperaemia | 2/85 (2.4%) | 2 | 3/84 (3.6%) | 4 | 3/88 (3.4%) | 4 | 2/85 (2.4%) | 2 | 1/84 (1.2%) | 1 | 1/88 (1.1%) | 1 |
Photophobia | 6/85 (7.1%) | 6 | 4/84 (4.8%) | 4 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 2/84 (2.4%) | 2 | 0/88 (0%) | 0 |
Posterior Capsule Opacification | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Refraction Disorder | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Swelling Of Eyelid | 1/85 (1.2%) | 1 | 6/84 (7.1%) | 6 | 1/88 (1.1%) | 1 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Vision Blurred | 3/85 (3.5%) | 3 | 2/84 (2.4%) | 2 | 1/88 (1.1%) | 2 | 1/85 (1.2%) | 1 | 2/84 (2.4%) | 2 | 2/88 (2.3%) | 2 |
Visual Acuity Reduced | 1/85 (1.2%) | 1 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Visual Impairment | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Vitreous Floaters | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||
Constipation | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Inguinal Hernia | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Nausea | 3/85 (3.5%) | 4 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
General disorders | ||||||||||||
Instillation Site Irritation | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Instillation Site Pain | 2/85 (2.4%) | 2 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Infections and infestations | ||||||||||||
Bronchitis | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 2/84 (2.4%) | 2 | 0/88 (0%) | 0 |
Hordeolum | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 2/84 (2.4%) | 3 | 0/88 (0%) | 0 |
Influenza | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Kidney Infection | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Nasopharyngitis | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 2/88 (2.3%) | 2 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Sinusitis | 1/85 (1.2%) | 1 | 1/84 (1.2%) | 1 | 3/88 (3.4%) | 3 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Upper Respiratory Tract | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 3/85 (3.5%) | 3 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Urinary Tract Infection | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Viral Infection | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||
Back Injury | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Humerus Fracture | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Ligament Sprain | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Superficial Injury Of Eye | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||
Arthritis | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Bursitis | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Tendonitis | 0/85 (0%) | 0 | 2/84 (2.4%) | 2 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Nervous system disorders | ||||||||||||
Dizziness | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Headache | 8/85 (9.4%) | 9 | 5/84 (6%) | 5 | 4/88 (4.5%) | 4 | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Hypoaesthesia | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Migraine | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Migraine With Aura | 1/85 (1.2%) | 1 | 1/84 (1.2%) | 2 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Renal and urinary disorders | ||||||||||||
Bladder Prolapse | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||
Asthma | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 |
Cough | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Dysphonia | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Oropharyngeal Pain | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Sinus Congestion | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Throat Irritation | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||||
Dermatitis | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 1/88 (1.1%) | 1 |
Rash | 0/85 (0%) | 0 | 1/84 (1.2%) | 1 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Vascular disorders | ||||||||||||
Hot Flush | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Lymphoedema | 0/85 (0%) | 0 | 0/84 (0%) | 0 | 0/88 (0%) | 0 | 1/85 (1.2%) | 1 | 0/84 (0%) | 0 | 0/88 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Maria De Pizzol, BSc |
---|---|
Organization | Dompé farmaceutici SpA |
Phone | +39 02 583831 |
info@pec.dompe.it |
- NGF0118