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NGF0112: Study to Evaluate Safety, Tolerability and Pharmacokinetics of rhNGF Eye Drops in Healthy Volunteers

Sponsor
Dompé Farmaceutici S.p.A (Industry)
Overall Status
Completed
CT.gov ID
NCT01744704
Collaborator
Covance (Industry)
74
Enrollment
2
Locations
11
Arms
8
Duration (Months)
37
Patients Per Site
4.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the safety and tolerability of single and multiple ascending doses of rhNGF when administered as eye drops in healthy subjects.

Condition or Disease Intervention/Treatment Phase
  • Drug: rhNGF 0.5 µg/mL Sentinel
  • Drug: rhNGF 5 µg/mL Sentinel
  • Drug: rhNGF 20 µg/mL Sentinel
  • Drug: rhNGF 20 µg/mL Part A
  • Drug: rhNGF 60 µg/mL Part A
  • Drug: rhNGF 180 µg/mL Part A
  • Drug: rhNGF 20 µg/mL Part B
  • Drug: rhNGF 60 µg/mL Part B
  • Drug: rhNGF 180 µg/mL Part B
  • Drug: Placebo Part A
  • Drug: Placebo Part B
 Phase 1

Detailed Description

This is a Phase I, randomised, double-masked, placebo-controlled eye drops administration study of rh-NGF in healthy male and female subjects.

This study consists of a single ascending dose part (part 0 one drop single application). Then single ascending dose part (part A; one drop three times a day) and a multiple ascending dose part (part B; one drop three times a day for five days). All parts of the study will consist of 3 ascending dose levels.

In order to support the dose escalation MAD phase from Covance, Basel to Covance, Leeds, an additional cohort (0M) will be conducted at Covance, Leeds at the same dose level as cohort 1M to ensure a degree of consistency between the two sites, i.e. that no dose escalation stopping criteria were met at either site.

In Part 0, each ascending dose cohort will include 3 subjects treated with one dose of rh-NGF.

In part A, each ascending dose cohort will include 6 subjects treated with rh-NGF and 2 with placebo.

In part B, each ascending dose cohort will include 9 subjects treated with rh-NGF drug and 3 with placebo, in addition to cohort 0M, which will include 3 subjects treated with rh-NGF and 1 with placebo

Study Design

Study Type:
Interventional
Actual Enrollment :
74 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Basic Science
Official Title:
Phase I, Randomised, Double-masked, Placebo-controlled, Combined Single and Multiple Ascending Dose Study to Evaluate Safety, Tolerability and Pharmacokinetics of rhNGF Eye Drops in Healthy Male and Female Volunteers
Study Start Date :
Jul 1, 2012
Actual Primary Completion Date :
Feb 1, 2013
Actual Study Completion Date :
Mar 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: rhNGF 0.5 µg/mL Sentinel

1 x 35 µL drop 3 subjects

Drug: rhNGF 0.5 µg/mL Sentinel
In Part 0, all subjects received one 35-μL drop of rh-NGF at an appropriate concentration in the study eye (right or left) according to the randomisation list to achieve the required dose level
Other Names:
  • Recombinant Human Nerve Growth Factor

    		•
    Experimental: rhNGF 5 µg/mL Sentinel

    1 x 35 µL drop 3 subjects

    Drug: rhNGF 5 µg/mL Sentinel
    Part 0 represented a sentinel group.
    Other Names:
  • Recombinant Human Nerve Growth Factor

    		•
    Experimental: rhNGF 60 µg/mL Part A

    3 x 35 µL drops applied at 4 h intervals 6 subjects

    Drug: rhNGF 60 µg/mL Part A
    In Part A, all subjects received one 35-μL drop of rh-NGF at an appropriate concentration or placebo in their study eye (right or left) according to the randomisation list (and 1 drop of placebo in the non-study eye). This occurred q4h on Day 1 to achieve the required fractionated single dose level.
    Other Names:
  • Recombinant Human Nerve Growth Factor

    		•
    Experimental: rhNGF 20 µg/mL Sentinel

    1 x 35 µL drop 3 subjects

    Drug: rhNGF 20 µg/mL Sentinel
    In Part 0, all subjects received one 35-μL drop of rh-NGF at an appropriate concentration in the study eye (right or left) according to the randomisation list to achieve the required dose level
    Other Names:
  • Recombinant Human Nerve Growth Factor

    		•
    Experimental: rhNGF 20 µg/mL Part A

    3 x 35 µL drops applied at 4 h intervals 6 subjects

    Drug: rhNGF 20 µg/mL Part A
    In Part A, all subjects received one 35-μL drop of rh-NGF at an appropriate concentration or placebo in their study eye (right or left) according to the randomisation list (and 1 drop of placebo in the non-study eye). This occurred q4h on Day 1 to achieve the required fractionated single dose level.
    Other Names:
  • Recombinant Human Nerve Growth Factor

    		•
    Experimental: rhNGF 180 µg/mL Part A

    3 x 35 µL drops applied at 4 h intervals 6 subjects

    Drug: rhNGF 180 µg/mL Part A
    In Part A, all subjects received one 35-μL drop of rh-NGF at an appropriate concentration or placebo in their study eye (right or left) according to the randomisation list (and 1 drop of placebo in the non-study eye). This occurred q4h on Day 1 to achieve the required fractionated single dose level.
    Other Names:
  • Recombinant Human Nerve Growth Factor

    		•
    Placebo Comparator: Placebo Part A

    3 x 35 µL drops applied at 4 h intervals 6 subjects

    Drug: Placebo Part A
    In Part A, all subjects received one 35-μL drop of rh-NGF at an appropriate concentration or placebo in their study eye (right or left) according to the randomisation list (and 1 drop of placebo in the non-study eye). This occurred q4h on Day 1 to achieve the required fractionated single dose level.
    Other Names:
  • Vehicle

    		•
    Experimental: rhNGF 20 µg/mL Part B

    3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 12 subjects

    Drug: rhNGF 20 µg/mL Part B
    In Part B, as planned 3 dose levels of rh-NGF or placebo eye drops were studied in a total of 40 healthy subjects.
    Other Names:
  • Recombinant Human Nerve Growth Factor

    		•
    Experimental: rhNGF 60 µg/mL Part B

    3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects

    Drug: rhNGF 60 µg/mL Part B
    In Part B, all subjects received one 35-μL drop of rh-NGF at an appropriate concentration or placebo in their study eye (right or left) according to the randomisation list (and 1 drop of placebo in the non-study eye). This occurred q4h for 5 days to achieve the required multiple fractionated dose level.
    Other Names:
  • Recombinant Human Nerve Growth Factor

    		•
    Experimental: rhNGF 180 µg/mL Part B

    3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects

    Drug: rhNGF 180 µg/mL Part B
    In Part B, all subjects received one 35-μL drop of rh-NGF at an appropriate concentration or placebo in their study eye (right or left) according to the randomisation list (and 1 drop of placebo in the non-study eye). This occurred q4h for 5 days to achieve the required multiple fractionated dose level.
    Other Names:
  • Recombinant Human Nerve Growth Factor

    		•
    Placebo Comparator: Placebo Part B

    3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects

    Drug: Placebo Part B
    In Part B, all subjects received one 35-μL drop of rh-NGF at an appropriate concentration or placebo in their study eye (right or left) according to the randomisation list (and 1 drop of placebo in the non-study eye). This occurred q4h for 5 days to achieve the required multiple fractionated dose level.
    Other Names:
  • Vehicle

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Changes in VAS Ocular Tolerability [Day -1, Day 1, Day 5, Day 15 (FU)]

      A global ocular discomfort score was determined using a 100 mm visual analogue scale (VAS) on which 0 means no symptoms and 100 means the worst possible discomfort. This evaluation was performed before any ophthalmic assessment at a given study visit. Specific ocular symptoms to be assessed with the VAS included: foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia. Part 0: VAS evaluated on days -1, 1, 3, 10 (FU) Part A: VAS evaluated on days -1, 1, 3, 10 (FU) Part B: VAS evaluated on days -1, 1, 5, 15 (FU) Follow up (FU) refers to participants' last available assessment. The Outcome Measure Time Points and Data Table refers to Part B.

    2. Change in Best Corrected Distance Visual Acuity (BCDVA) [Day -1, Day 1, Day 5, Day 15 (FU)]

      Best corrected distance visual acuity measured using the ETDRS (Early Treatment Diabetic Retinopathy Study) score. In this population, the scores range from -6 (worse visus) to 3 (best visus). The study includes Part 0, Part A and Part B. In Part B BCDVA was evaluated on days -1, 1, 5, 15 (FU). Follow up (FU) refers to participants' last available assessment.

    3. Change in Mean Tear Film Break up Time (TFBUT) [Day -1, Day 1, Day 5, Day 15 (FU)]

      Tear film break-up time was assessed by slit lamp examination (SLE). The shorter is the tear film break-up time, the worse is the dry eye symptom severity. The study includes Part 0, Part A and Part B. In Part B this endpoint was evaluated on days -1, 1, 5, 15 (FU). Follow up (FU) refers to participants' last available assessment.

    4. Change in Mean Corneal Fluorescein Staining [Day -1, Day 1, Day 5, Day 15 (FU)]

      Slit lamp examination was used to assess the eyelid margin, conjunctiva, cornea, anterior chamber, iris and lens with the instillation of fluorescein to evaluate corneal fluorescein staining (modified Oxford scale). This is 7-point ordinal scale that scores 0, 0.5, and 1 to 5. On this scale the score 0 corresponds to no staining dots (complete corneal clearing) and the score 0.5 corresponds to three or less staining dots. The higher is the number of dots, the higher and worse is the score. The study includes Part 0, Part A and Part B. In Part B the endpoint was evaluated on days -1, 1, 5, 15 (FU).

    5. Change in Intraocular Pressure (IOP) [Screening, Day 7, Day 15 (FU)]

      Intraocular pressure was determined using Goldmann applanation tonometry. The study includes Part 0, Part A and Part B. In Part B this endpoint was evaluated at screening and on days 7, 15 (FU). Follow up (FU) refers to participants' last available assessment.

    6. Percentage of Abnormal Findings in Dilated Fundus Ophthalmoscopy [Part B - Day 7]

      Dilated fundus ophthalmoscopy (DFO) is used to view the eye's interior, allowing assessment of the retina/macula/choroid, optic nerve head, blood vessels, and other features. The outcome can be normal or abnormal. The study includes Part 0, Part A and Part B. In Part B this endpoint was evaluated on day 7.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Male or female subjects, aged between 18 and 60 years, inclusive.

    • Subject has to be able to communicate well with the investigator, understands and complies with the requirements of the study, and understands and signs the written volunteer informed consent form.

    • Subject's systemic and ocular medical history must be considered normal in the opinion of the investigator at the Screening and Baseline visits.

    • Best corrected distance visual acuity (BCDVA) score ≤ 0.00 LogMAR (≥83 ETDRS letters, 20/20 Snellen or 1.0 decimal fraction) in each eye at the Screening and Baseline visits.

    • Normal anterior segment on external and slit lamp examination in both eyes at the Screening and Baseline visits.

    • Normal posterior segment on fundus ophthalmoscopic examination in both eyes at the Screening and Baseline visits.

    • Subject must be considered in good systemic health in the opinion of the investigator at the Screening and Baseline visits, as determined by:

    1. Subject's body mass index is between 18.5 and 30.4 kg/m2 inclusive

    2. A pre-study physical examination with no clinically significant abnormalities.

    3. Vital signs within clinically acceptable ranges for the purposes of the study (sitting systolic blood pressure [BP] ≥ 90 mmHg and ≤ 150 mmHg; diastolic BP ≥ 50 mmHg and ≤ 95 mmHg; heart rate (pulse rate) ≥ 40 and ≤ 100 beats per minute; oral body temperature ≥ 35.5°C and ≤ 37.5°C).

    4. An ECG with no clinically significant abnormalities, in the opinion of the Investigator.

    5. Pre-study clinical laboratory findings within normal range or not deemed clinically significant in the opinion of the investigator if outside of the normal range

    • Female subjects will be:

    • either post menopausal where post menopause is defined as the period following peri-menopause, i.e. postmenopausal after 12 months without a menstrual period and with a serum FSH value within the reference range for postmenopausal females at Screening

    • or permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy)

    • or be using 2 different forms of highly effective contraception throughout the study.

    Male subjects with female partners of child-bearing potential must use 2 different forms of highly effective contraception throughout the study and for a further 3 months after the follow-up visit and all male subjects must be willing to avoid donating sperm during this time.

    Exclusion Criteria:

    • Subject has had a clinically significant illness in the 6 weeks before screening in the opinion of the investigator.

    • Subject is not suitable to participate in the study in the opinion of the investigator

    • Subject has participated in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.

    • Subject has had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or has a clinically significant allergy to drugs, foods or other materials (in the opinion of the investigator).

    • Administration of any topical ocular (prescription or over the counter including artificial tears) or systemic medication including herbal product or fish oil preparations within 14 days before the first dose of study drug. Vitamins and mineral supplements not containing other substances are allowed until 96 hours before each dose if considered by the Investigator unlikely to interfere with the study results. Paracetamol at doses of at most 2 grams per day and ibuprofen at doses of at most 1200 mg per day for no more than 3 consecutive days or 6 non-consecutive days are allowed. Oral, injectable and implantable hormonal contraceptives are allowed without restrictions for female subjects. Longer exclusion periods apply for:

    1. amiodarone and hydroxychloroquine (210 days),

    2. monoclonal antibodies/ immunoglobulins/ other therapeutic proteins (120 days)

    3. Experimental drugs with a half life known to the Study Unit: Five half lives plus 2 weeks

    4. Experimental drugs with a half life unknown to the Study Unit: 120 days

    5. chloroquine and flunarizine (100 days)

    6. fluoxetine (75 days),

    7. benzodiazepines different from midazolam, lorazepam and triazolam, chlorpromazine, mephenytoin, nortryptyline, phenobarbital, primidone, carbamazepine, phenytoin and phenprocoumon (35 days).

    • Subject has a significant history of drug/solvent abuse (within the last 2 years) or a positive drugs of abuse test at any time during the study.

    • Subject has a history of alcohol abuse (within the last 2 years) or currently drinks in excess of 28 units per week or has a positive alcohol breath test at any time during the study.

    • Subject is a smoker or has smoked in the 6 months prior to dosing.

    • Subject who has a positive human immunodeficiency virus (HIV) screen, hepatitis B screen or hepatitis C screen.

    • Subject has donated blood or blood products (e.g., plasma or platelets) within the 3 months prior to screening.

    • Subject has a partner who will be pregnant or breastfeeding during the study

    • Pregnant or breastfeeding female or those with a positive pregnancy test or who will not use a medically acceptable contraceptive method from selection and during the study

    • Subject having used any glucocorticosteroid by any route in the last 30 days whichever the route of administration, or any medication by ocular or nasal administration route from 30 days before screening.

    • Subjects currently diagnosed with any active ocular disease, even if mild, other than refractive error.

    • Subject with history of ocular surgery, including laser refractive surgery

    • Subject using a contact lens within 7 days prior administration of the first dose

    • Intraocular pressure (IOP) >= 22 mmHg in either eye

    • Presence of any corneal opacity or corneal fluorescein staining >0.5 grade using the modified Oxford scale

    • Schirmer's test without anesthesia <= 9 mm/5 minutes

    • Tear film break up time < 8 seconds

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Covance Basel Research Unit AG - Lettenweg 118 - Allschwil Switzerland CH - 4123
    2 COVANCE CLINICAL RESEARCH UNIT Ltd - Springfield House - Hyde Street Leeds United Kingdom LS2 9LH

    Sponsors and Collaborators

    • Dompé Farmaceutici S.p.A
    • Covance

    Investigators

    • Principal Investigator: Thierry Kamtchoua, MD, Covance Basel Research Unit AG
    • Principal Investigator: Ashley Brooks, MBChB, Covance
    • Study Director: Pier Adelchi Ruffini, MD, Dompé s.p.a.Via San Martino, 12 - 20122 Milan, Italy
    • Study Director: Mauro P Ferrari, PharmD, Dompé s.p.a. - Via San Martino, 12 - 20122 Milan, Italy

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Dompé Farmaceutici S.p.A
    ClinicalTrials.gov Identifier:
    NCT01744704
    Other Study ID Numbers:
    • NGF0112
    • 2012-004302-10
    First Posted:
    Dec 7, 2012
    Last Update Posted:
    Sep 9, 2019
    Last Verified:
    Jul 1, 2019
    Keywords provided by Dompé Farmaceutici S.p.A
    Nerve Growth Factor
    Ophthalmic Solutions
    Eye Drops
    rh-NGF
    Additional relevant MeSH terms:
    Mitogens

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 60 µg/mL Part A rhNGF 20 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 20 µg/mL Part B Cohort 0M rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Arm/Group Description 1 x 35 µL drop 3 subjects rhNGF 0.5 µg/mL Sentinel: one drop administration 1 x 35 µL drop 3 subjects rhNGF 5 µg/mL Sentinel 1 x 35 µL drop 3 subjects rhNGF 20 µg/mL Sentinel 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 60 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 20 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 180 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects Placebo Part A 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subject rhNGF 20 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 3 subjects rhNGF 20 µg/mL Part B cohort 0M 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 60 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 180 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects Placebo Part B
    Period Title: Overall Study
    STARTED 3 3 3 6 6 7 6 9 3 9 9 10
    COMPLETED 3 3 3 6 6 7 6 9 3 9 9 10
    NOT COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A rhNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B Total
    Arm/Group Description 1 x 35 µL drop 3 subjects rhNGF 0.5 µg/mL Sentinel: one drop administration 1 x 35 µL drop 3 subjects rhNGF 5 µg/mL Sentinel 1 x 35 µL drop 3 subjects rhNGF 20 µg/mL Sentinel 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 20 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 60 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 180 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects Placebo Part A 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subject rhNGF 20 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 60 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 180 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects Placebo Part B Total of all reporting groups
    Overall Participants 3 3 3 6 6 7 6 12 9 9 10 74
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    30
    (7)
    47
    (9.2)
    29
    (11.9)
    46
    (10)
    36
    (9.4)
    42
    (17.8)
    42
    (9)
    41
    (12.1)
    36
    (14.7)
    29
    (10.3)
    36
    (12.6)
    40.2
    (11.8)
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    2
    66.7%
    1
    33.3%
    1
    16.7%
    1
    16.7%
    3
    42.9%
    2
    33.3%
    4
    33.3%
    5
    55.6%
    1
    11.1%
    2
    20%
    24
    32.4%
    Male
    1
    33.3%
    1
    33.3%
    2
    66.7%
    5
    83.3%
    5
    83.3%
    4
    57.1%
    4
    66.7%
    8
    66.7%
    4
    44.4%
    8
    88.9%
    8
    80%
    50
    67.6%
    Region of Enrollment (participants) [Number]
    United Kingdom
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    25%
    9
    100%
    9
    100%
    8
    80%
    29
    39.2%
    Switzerland
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    6
    100%
    7
    100%
    6
    100%
    9
    75%
    0
    0%
    0
    0%
    2
    20%
    45
    60.8%

    Outcome Measures

    1. Primary Outcome
    Title Changes in VAS Ocular Tolerability
    Description A global ocular discomfort score was determined using a 100 mm visual analogue scale (VAS) on which 0 means no symptoms and 100 means the worst possible discomfort. This evaluation was performed before any ophthalmic assessment at a given study visit. Specific ocular symptoms to be assessed with the VAS included: foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia. Part 0: VAS evaluated on days -1, 1, 3, 10 (FU) Part A: VAS evaluated on days -1, 1, 3, 10 (FU) Part B: VAS evaluated on days -1, 1, 5, 15 (FU) Follow up (FU) refers to participants' last available assessment. The Outcome Measure Time Points and Data Table refers to Part B.
    Time Frame Day -1, Day 1, Day 5, Day 15 (FU)

    Outcome Measure Data

    Analysis Population Description
    Safety population: consisted of all subjects randomised into the study and receiving a dose of study medication.
    Arm/Group Title rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A rhNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Arm/Group Description 1 x 35 µL drop 3 subjects rhNGF 0.5 µg/mL Sentinel: one drop administration 1 x 35 µL drop 3 subjects rhNGF 5 µg/mL Sentinel 1 x 35 µL drop 3 subjects rhNGF 20 µg/mL Sentinel 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 20 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 60 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 180 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects Placebo Part A 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subject rhNGF 20 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 60 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 180 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects Placebo Part B
    Measure Participants 3 3 3 6 6 7 6 12 9 9 10
    Foreign body sensation - Day 1 (8h) vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0)
    3
    (7.3)
    0
    (0)
    0
    (0)
    0.4
    (0)
    0
    (0)
    0
    (0.5)
    0
    (0.5)
    0
    (0.8)
    Foreign body sensation - Day 5 vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    1
    (2.6)
    0
    (0.5)
    0
    (0.7)
    0
    (0.7)
    Foreign body sensation - FU vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0.6)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.5)
    0
    (0.4)
    0
    (0.6)
    Burning/Stinging - Day 1 (8h) vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0.6)
    2
    (4.9)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.3)
    0
    (0.5)
    0
    (0.6)
    0
    (0.3)
    Burning/Stinging - Day 5 vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    1
    (3.5)
    0
    (0.4)
    0
    (0.5)
    0
    (0.4)
    Burning/Stinging - FU vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.3)
    0
    (0.5)
    0
    (0.4)
    0
    (0.6)
    Itching - Day 1 (8h) vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0)
    0
    (0.4)
    0
    (0)
    0
    (0)
    0
    (0.4)
    0
    (0.3)
    0
    (0.3)
    0
    (0.7)
    0
    (0.4)
    Itching - Day 5 vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0.6)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.4)
    0
    (0.3)
    0
    (0.3)
    0
    (0.4)
    0
    (0.5)
    Itching - FU vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.3)
    0
    (0.7)
    0
    (0.6)
    0
    (0)
    Pain - Day 1 (8h) vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.4)
    0
    (0.3)
    0
    (0.7)
    0
    (0.7)
    0
    (0.8)
    Pain - Day 5 vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.4)
    0
    (0.3)
    1
    (3.5)
    4
    (6.5)
    0
    (1.1)
    Pain - FU vs Day -1
    -1
    (1.2)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.4)
    0
    (0.3)
    0
    (0.7)
    0
    (0.4)
    0
    (0.7)
    Sticky feeling - Day 1 (8h) vs Day -1
    -1
    (1.7)
    0
    (0)
    -3
    (4.6)
    -1
    (1.6)
    0
    (0.8)
    0
    (0)
    1
    (2.4)
    0
    (0)
    0
    (0.7)
    3
    (7.6)
    0
    (0.4)
    Sticky feeling - Day 5 vs Day -1
    -1
    (1.7)
    0
    (0)
    -2
    (4.9)
    -1
    (1.6)
    0
    (0.8)
    0
    (0)
    0
    (0.4)
    0
    (0.3)
    0
    (0.5)
    1
    (3.6)
    0
    (0.6)
    Sticky feeling - FU vs Day -1
    -1
    (1.7)
    0
    (0)
    -3
    (4.6)
    -1
    (1.6)
    0
    (0.8)
    0
    (0)
    0
    (0.4)
    0
    (0.3)
    0
    (0.5)
    0
    (0.4)
    0
    (0.3)
    Blurred vision - Day 1 (8h) vs Day -1
    -2
    (1.5)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.4)
    0
    (0)
    0
    (0.5)
    0
    (0.3)
    0
    (0.5)
    Blurred vision - Day 5 vs Day -1
    -2
    (1.5)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.3)
    0
    (0.5)
    Blurred vision - FU vs Day -1
    -2
    (1.5)
    0
    (0)
    0
    (0.6)
    0
    (0.4)
    0
    (0)
    0
    (0)
    0
    (0.4)
    0
    (0)
    0
    (0.3)
    1
    (0.5)
    0
    (0.5)
    Photophobia - Day 1 (8h) vs Day -1
    -1
    (1.7)
    0
    (0)
    0
    (0)
    1
    (3.3)
    1
    (1.6)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.5)
    0
    (0.6)
    0
    (0.5)
    Photophobia - Day 5 vs Day -1
    -1
    (1.7)
    0
    (0)
    0
    (0.6)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.8)
    1
    (2.0)
    0
    (0.5)
    0
    (0.7)
    0
    (0.5)
    Photophobia - FU vs Day -1
    -1
    (1.7)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0.8)
    0
    (0)
    0
    (0.4)
    0
    (0)
    0
    (0.7)
    0
    (0.7)
    0
    (0.5)
    2. Primary Outcome
    Title Change in Best Corrected Distance Visual Acuity (BCDVA)
    Description Best corrected distance visual acuity measured using the ETDRS (Early Treatment Diabetic Retinopathy Study) score. In this population, the scores range from -6 (worse visus) to 3 (best visus). The study includes Part 0, Part A and Part B. In Part B BCDVA was evaluated on days -1, 1, 5, 15 (FU). Follow up (FU) refers to participants' last available assessment.
    Time Frame Day -1, Day 1, Day 5, Day 15 (FU)

    Outcome Measure Data

    Analysis Population Description
    Safety population consisted of all subjects randomised into the study and receiving a dose of study medication.
    Arm/Group Title rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A rhNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Arm/Group Description 1 x 35 µL drop 3 subjects rhNGF 0.5 µg/mL Sentinel: one drop administration 1 x 35 µL drop 3 subjects rhNGF 5 µg/mL Sentinel 1 x 35 µL drop 3 subjects rhNGF 20 µg/mL Sentinel 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 20 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 60 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 180 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects Placebo Part A 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subject rhNGF 20 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 60 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 180 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects Placebo Part B
    Measure Participants 3 3 3 6 6 7 6 12 9 9 10
    Day 1 vs Day-1
    1
    (0.6)
    3
    (0.6)
    -6
    (3.1)
    3
    (1.6)
    0
    (0.4)
    -0
    (1.4)
    1
    (1.6)
    1
    (2.7)
    0
    (3.7)
    0
    (3.6)
    0
    (3.1)
    Day 5 vs Day-1
    1
    (2.3)
    0.0
    (4.7)
    1
    (2.1)
    1
    (2.6)
    1
    (2.5)
    0
    (2.8)
    -1
    (2.0)
    1
    (2.7)
    1
    (2.9)
    0
    (3.3)
    0
    (3.8)
    Day 15 (FU) vs Day-1
    2
    (2.5)
    2
    (1.0)
    -1
    (2.9)
    2
    (4.0)
    2
    (1.9)
    0
    (2.3)
    0
    (3.2)
    1
    (2.4)
    1
    (2.4)
    2
    (3.7)
    0
    (2.1)
    3. Primary Outcome
    Title Change in Mean Tear Film Break up Time (TFBUT)
    Description Tear film break-up time was assessed by slit lamp examination (SLE). The shorter is the tear film break-up time, the worse is the dry eye symptom severity. The study includes Part 0, Part A and Part B. In Part B this endpoint was evaluated on days -1, 1, 5, 15 (FU). Follow up (FU) refers to participants' last available assessment.
    Time Frame Day -1, Day 1, Day 5, Day 15 (FU)

    Outcome Measure Data

    Analysis Population Description
    Safety population: consisted of all subjects randomised into the study and receiving a dose of study medication.
    Arm/Group Title rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A rhNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Arm/Group Description 1 x 35 µL drop 3 subjects rhNGF 0.5 µg/mL Sentinel: one drop administration 1 x 35 µL drop 3 subjects rhNGF 5 µg/mL Sentinel 1 x 35 µL drop 3 subjects rhNGF 20 µg/mL Sentinel 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 20 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 60 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 180 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects Placebo Part A 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subject rhNGF 20 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 60 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 180 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects Placebo Part B
    Measure Participants 3 3 3 6 6 7 6 12 9 9 10
    Day 1 vs Day -1
    1.7
    (1.89)
    0.0
    (0.5)
    -2.6
    (2.95)
    0.4
    (0.86)
    -0.5
    (0.64)
    -0.4
    (1.93)
    0.0
    (0.67)
    0.5
    (1.14)
    0.4
    (0.96)
    0.1
    (1.11)
    0.2
    (0.79)
    Day 5 vs Day -1
    -1.2
    (1.62)
    -0.3
    (1.04)
    0.9
    (1.21)
    0.1
    (0.69)
    -0.1
    (0.85)
    0.0
    (1.64)
    -0.7
    (1.53)
    -0.2
    (1.76)
    -0.4
    (1.52)
    0.2
    (2.03)
    -0.2
    (1.03)
    Day 15 (FU) vs Day -1
    -1.4
    (1.65)
    0.2
    (0.29)
    -0.9
    (1.4)
    -0.1
    (1.32)
    0.4
    (0.77)
    -0.6
    (0.69)
    1.0
    (1.22)
    0.1
    (1.07)
    -0.4
    (1.83)
    -0
    (1.48)
    0.0
    (1.08)
    4. Primary Outcome
    Title Change in Mean Corneal Fluorescein Staining
    Description Slit lamp examination was used to assess the eyelid margin, conjunctiva, cornea, anterior chamber, iris and lens with the instillation of fluorescein to evaluate corneal fluorescein staining (modified Oxford scale). This is 7-point ordinal scale that scores 0, 0.5, and 1 to 5. On this scale the score 0 corresponds to no staining dots (complete corneal clearing) and the score 0.5 corresponds to three or less staining dots. The higher is the number of dots, the higher and worse is the score. The study includes Part 0, Part A and Part B. In Part B the endpoint was evaluated on days -1, 1, 5, 15 (FU).
    Time Frame Day -1, Day 1, Day 5, Day 15 (FU)

    Outcome Measure Data

    Analysis Population Description
    Safety population: consisted of all subjects randomised into the study and receiving a dose of study medication.
    Arm/Group Title rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A hNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Arm/Group Description 1 x 35 µL drop 3 subjects rhNGF 0.5 µg/mL Sentinel: one drop administration 1 x 35 µL drop 3 subjects rhNGF 5 µg/mL Sentinel 1 x 35 µL drop 3 subjects rhNGF 20 µg/mL Sentinel 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 20 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 60 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 180 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects Placebo Part A 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subject rhNGF 20 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 60 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 180 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects Placebo Part B
    Measure Participants 3 3 3 6 6 7 6 12 9 9 10
    Day 1 vs Day -1
    1.7
    (1.89)
    0.0
    (0.50)
    -2.6
    (2.95)
    0.4
    (0.86)
    -0.5
    (0.64)
    -0.4
    (1.93)
    0.0
    (0.67)
    0.2
    (1.14)
    0.4
    (0.96)
    0.1
    (1.11)
    0.2
    (0.79)
    Day 5 vs Day -1
    -1.2
    (1.62)
    -0.3
    (1.04)
    -0.9
    (1.21)
    0.1
    (0.69)
    -0.1
    (0.85)
    0.0
    (1.64)
    -0.7
    (1.53)
    -0.2
    (1.76)
    -0.4
    (1.52)
    -0.2
    (2.03)
    -0.2
    (1.03)
    Day 15 (FU) vs Day -1
    -1.4
    (1.65)
    0.2
    (0.29)
    -0.9
    (1.40)
    -0.1
    (1.32)
    0.4
    (0.77)
    -0.6
    (0.69)
    1.0
    (1.22)
    0.1
    (1.07)
    -0.4
    (1.83)
    -0.0
    (1.48)
    0.0
    (1.08)
    5. Primary Outcome
    Title Change in Intraocular Pressure (IOP)
    Description Intraocular pressure was determined using Goldmann applanation tonometry. The study includes Part 0, Part A and Part B. In Part B this endpoint was evaluated at screening and on days 7, 15 (FU). Follow up (FU) refers to participants' last available assessment.
    Time Frame Screening, Day 7, Day 15 (FU)

    Outcome Measure Data

    Analysis Population Description
    Safety population: consisted of all subjects randomised into the study and receiving a dose of study medication.
    Arm/Group Title rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A rhNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Arm/Group Description 1 x 35 µL drop 3 subjects rhNGF 0.5 µg/mL Sentinel: one drop administration 1 x 35 µL drop 3 subjects rhNGF 5 µg/mL Sentinel 1 x 35 µL drop 3 subjects rhNGF 20 µg/mL Sentinel 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 20 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 60 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 180 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects Placebo Part A 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subject rhNGF 20 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 60 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 180 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects Placebo Part B
    Measure Participants 3 3 3 6 6 7 6 12 9 9 10
    Day 7 vs screening
    1
    (2.0)
    -1
    (1.5)
    -1
    (2.6)
    1
    (1.8)
    1
    (3.9)
    1
    (1.6)
    -2
    (1.8)
    -1
    (2.0)
    0
    (3)
    -2
    (3.7)
    -2
    (2.8)
    Day 15 (FU) vs screening
    -1
    (2.5)
    1
    (0.6)
    -1
    (1.0)
    1
    (2.7)
    -1
    (3.3)
    1
    (3.2)
    -2
    (2.8)
    0
    (5.3)
    -1
    (3.3)
    -1
    (3.1)
    -3
    (3.4)
    6. Primary Outcome
    Title Percentage of Abnormal Findings in Dilated Fundus Ophthalmoscopy
    Description Dilated fundus ophthalmoscopy (DFO) is used to view the eye's interior, allowing assessment of the retina/macula/choroid, optic nerve head, blood vessels, and other features. The outcome can be normal or abnormal. The study includes Part 0, Part A and Part B. In Part B this endpoint was evaluated on day 7.
    Time Frame Part B - Day 7

    Outcome Measure Data

    Analysis Population Description
    Safety population: consisted of all subjects randomised into the study and receiving a dose of study medication.
    Arm/Group Title rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 60 µg/mL Part A rhNGF 20 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Arm/Group Description 1 x 35 µL drop 3 subjects rhNGF 0.5 µg/mL Sentinel: one drop administration 1 x 35 µL drop 3 subjects rhNGF 5 µg/mL Sentinel 1 x 35 µL drop 3 subjects rhNGF 20 µg/mL Sentinel 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 60 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 20 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 180 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects Placebo Part A 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subject rhNGF 20 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 60 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 180 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects Placebo Part B
    Measure Participants 3 3 3 6 6 7 6 12 9 9 10
    Mean (Standard Deviation) [percentage of abnormal findings]
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A rhNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Arm/Group Description 1 x 35 µL drop 3 subjects rhNGF 0.5 µg/mL Sentinel: one drop administration 1 x 35 µL drop 3 subjects rhNGF 5 µg/mL Sentinel 1 x 35 µL drop 3 subjects rhNGF 20 µg/mL Sentinel 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 20 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 60 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects rhNGF 180 µg/mL Part A 3 x 35 µL drops applied at 4 h intervals 6 subjects Placebo Part A 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 12 subject rhNGF 20 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 60 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects rhNGF 180 µg/mL Part B 3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects Placebo Part B
    All Cause Mortality
    rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A rhNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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 / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A rhNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/12 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%)
    Other (Not Including Serious) Adverse Events
    rhNGF 0.5 µg/mL Sentinel rhNGF 5 µg/mL Sentinel rhNGF 20 µg/mL Sentinel rhNGF 20 µg/mL Part A rhNGF 60 µg/mL Part A rhNGF 180 µg/mL Part A Placebo Part A rhNGF 20 µg/mL Part B rhNGF 60 µg/mL Part B rhNGF 180 µg/mL Part B Placebo Part B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 0/6 (0%) 2/7 (28.6%) 3/6 (50%) 8/12 (66.7%) 6/9 (66.7%) 7/9 (77.8%) 6/10 (60%)
    Eye disorders
    Abnormals sensation in eye 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/9 (11.1%) 1 0/10 (0%) 0
    Vision Blurred 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/12 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/10 (0%) 0
    Conjunctivitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Eye irritation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 1/12 (8.3%) 1 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Photophobia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/12 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Eyelid irritation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/12 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Eye pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 2/9 (22.2%) 2 5/9 (55.6%) 5 1/10 (10%) 1
    Eye discharge 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/10 (0%) 0
    Eye pruritus 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/12 (8.3%) 1 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Eye swelling 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/10 (0%) 0
    Lacrimation increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/10 (0%) 0
    Visual impairment 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/10 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/12 (8.3%) 1 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    General disorders
    Vessel puncture site pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/12 (8.3%) 1 0/9 (0%) 0 0/9 (0%) 0 1/10 (10%) 1
    Catheter site related reaction 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 1/10 (10%) 1
    Infections and infestations
    Nasopharyngitis 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/12 (8.3%) 1 0/9 (0%) 0 1/9 (11.1%) 1 1/10 (10%) 1
    Injury, poisoning and procedural complications
    Ligament sprain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/12 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Investigations
    Corneal staining 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 1/10 (10%) 1
    Back pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/12 (8.3%) 1 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Joint stiffness 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/10 (0%) 0
    Muscle twitching 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/10 (0%) 0
    Osteoarthritis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/12 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Nervous system disorders
    Headache 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 2/12 (16.7%) 2 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Dizziness 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/10 (0%) 0
    Psychiatric disorders
    Depression 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/12 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Renal and urinary disorders
    Haematuria 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/12 (8.3%) 2 0/9 (0%) 0 0/9 (0%) 0 0/10 (0%) 0
    Reproductive system and breast disorders
    Dysmenorrhoea 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/12 (8.3%) 1 1/9 (11.1%) 1 0/9 (0%) 0 0/10 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/10 (0%) 0
    Nasal congestion 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/10 (0%) 0
    Orapharyngeal pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/12 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 1/10 (10%) 1

    Limitations/Caveats

    No limitations and caveats area defined.

    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 Flavio Mantelli, MD, PhD
    Organization Dompé s.p.a.
    Phone +39 0862 3381
    Email info@dompe.it
    Responsible Party:
    Dompé Farmaceutici S.p.A
    ClinicalTrials.gov Identifier:
    NCT01744704
    Other Study ID Numbers:
    • NGF0112
    • 2012-004302-10
    First Posted:
    Dec 7, 2012
    Last Update Posted:
    Sep 9, 2019
    Last Verified:
    Jul 1, 2019