CompletedNCT01744704NGF0112Updated Apr 19, 2024Results posted

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

A Phase 1 interventional study of rhNGF 0.5 µg/mL Sentinel and rhNGF 5 µg/mL Sentinel in Healthy, sponsored by Dompé Farmaceutici S.p.A. Completed at 2 sites in 2 countries. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-04-19.

Sponsored by Dompé Farmaceutici S.p.A · Phase 1, Interventional, and Basic science

Phase: Phase 1
Study type: Interventional
Enrollment: 74
Allocation: Randomized
Ages: 18 Years to 60 Years
Sex: All

Study 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.

Read the 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

Conditions studied

Healthy

Keywords

Nerve Growth Factor
Ophthalmic Solutions
Eye Drops
rh-NGF

In context

Lead sponsor

Dompé Farmaceutici S.p.A is the lead sponsor of 51 studies on the registry; 4 are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 18 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 60 Years
Sexes eligible: 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

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

Study design

Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 74 participants (actual)

Study arms

Experimental
rhNGF 0.5 µg/mL Sentinel
1 x 35 µL drop 3 subjects
Drug: rhNGF 0.5 µg/mL Sentinel
Experimental
rhNGF 5 µg/mL Sentinel
1 x 35 µL drop 3 subjects
Drug: rhNGF 5 µg/mL Sentinel
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
Experimental
rhNGF 20 µg/mL Sentinel
1 x 35 µL drop 3 subjects
Drug: rhNGF 20 µg/mL Sentinel
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
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
Placebo comparator
Placebo Part A
3 x 35 µL drops applied at 4 h intervals 6 subjects
Drug: Placebo Part A
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
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
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
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

Interventions

DrugrhNGF 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
Also known as: Recombinant Human Nerve Growth Factor
DrugrhNGF 5 µg/mL Sentinel
Part 0 represented a sentinel group.
Also known as: Recombinant Human Nerve Growth Factor
DrugrhNGF 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
Also known as: Recombinant Human Nerve Growth Factor
DrugrhNGF 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.
Also known as: Recombinant Human Nerve Growth Factor
DrugrhNGF 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.
Also known as: Recombinant Human Nerve Growth Factor
DrugrhNGF 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.
Also known as: Recombinant Human Nerve Growth Factor
DrugrhNGF 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.
Also known as: Recombinant Human Nerve Growth Factor
DrugrhNGF 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.
Also known as: Recombinant Human Nerve Growth Factor
DrugrhNGF 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.
Also known as: Recombinant Human Nerve Growth Factor
DrugPlacebo 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.
Also known as: Vehicle
DrugPlacebo 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.
Also known as: Vehicle

What researchers measure

Primary outcomes

Changes in VAS Ocular Tolerability
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)
Change in Best Corrected Distance Visual Acuity (BCDVA)
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)
Change in Mean Tear Film Break up Time (TFBUT)
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)
Change in Mean Corneal Fluorescein Staining
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)
Change in Intraocular Pressure (IOP)
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)
Percentage of Abnormal Findings in Dilated Fundus Ophthalmoscopy
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

Results

Posted Sep 9, 2019

Limitations and caveats

No limitations and caveats area defined.

Participant flow

Participant flow — Overall Study
Milestone	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
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

Outcome measures

PrimaryChanges in VAS Ocular Tolerability

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)
Reported as:: Mean · units on a scale

Changes in VAS Ocular Tolerability
units on a scale	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
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

PrimaryChange in Best Corrected Distance Visual Acuity (BCDVA)

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)
Reported as:: Mean · units on a scale

Change in Best Corrected Distance Visual Acuity (BCDVA)
units on a scale	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
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

PrimaryChange in Mean Tear Film Break up Time (TFBUT)

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)
Reported as:: Mean · seconds

Change in Mean Tear Film Break up Time (TFBUT)
seconds	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
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

PrimaryChange in Mean Corneal Fluorescein Staining

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)
Reported as:: Mean · Units on a scale

Change in Mean Corneal Fluorescein Staining
Units on a scale	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
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

PrimaryChange in Intraocular Pressure (IOP)

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)
Reported as:: Mean · mmHg

Change in Intraocular Pressure (IOP)
mmHg	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
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

PrimaryPercentage of Abnormal Findings in Dilated Fundus Ophthalmoscopy

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
Reported as:: Mean · percentage of abnormal findings

Percentage of Abnormal Findings in Dilated Fundus Ophthalmoscopy
percentage of abnormal findings	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
Percentage of Abnormal Findings in Dilated Fundus Ophthalmoscopy	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
rhNGF 0.5 µg/mL Sentinel	—	0/3 (0%)	0/3 (0%)
rhNGF 5 µg/mL Sentinel	—	0/3 (0%)	1/3 (33.3%)
rhNGF 20 µg/mL Sentinel	—	0/3 (0%)	1/3 (33.3%)
rhNGF 20 µg/mL Part A	—	0/6 (0%)	1/6 (16.7%)
rhNGF 60 µg/mL Part A	—	0/6 (0%)	0/6 (0%)
rhNGF 180 µg/mL Part A	—	0/7 (0%)	2/7 (28.6%)
Placebo Part A	—	0/6 (0%)	3/6 (50%)
rhNGF 20 µg/mL Part B	—	0/12 (0%)	8/12 (66.7%)
rhNGF 60 µg/mL Part B	—	0/9 (0%)	6/9 (66.7%)
rhNGF 180 µg/mL Part B	—	0/9 (0%)	7/9 (77.8%)
Placebo Part B	—	0/10 (0%)	6/10 (60%)

Most frequent other events

Showing 10 of 31

Most frequent other events
Event	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
Eye painEye disorders	0/3	0/3	0/3	0/6	0/6	0/7	0/6	0/12	2/9	5/9	1/10
Abnormals sensation in eyeEye disorders	0/3	1/3	1/3	1/6	0/6	0/7	0/6	1/6	0/7	1/9	0/10
NasopharyngitisInfections and infestations	0/3	0/3	1/3	0/6	0/6	0/7	0/6	1/12	0/9	1/9	1/10
HeadacheNervous system disorders	0/3	0/3	0/3	0/6	0/6	0/7	2/6	2/12	0/9	0/9	0/10
Vision BlurredEye disorders	0/3	0/3	0/3	1/6	0/6	0/7	1/6	0/12	0/9	1/9	0/10
ConjunctivitisEye disorders	0/3	0/3	0/3	1/6	0/6	0/7	0/6	0/12	0/9	0/9	0/10
Eyelid irritationEye disorders	0/3	0/3	0/3	0/6	0/6	0/7	1/6	0/12	0/9	0/9	0/10
OsteoarthritisMusculoskeletal and connective tissue disorders	0/3	0/3	0/3	0/6	0/6	0/7	1/6	0/12	0/9	0/9	0/10
Corneal stainingInvestigations	0/3	0/3	0/3	1/6	0/6	0/7	0/6	0/12	0/9	0/9	0/10
DepressionPsychiatric disorders	0/3	0/3	0/3	0/6	0/6	0/7	1/6	0/12	0/9	0/9	0/10

Baseline characteristics

Age, Continuous
Age, Continuous(years)	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
Mean	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
Sex: Female, Male(Participants)	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
Female	2	2	1	1	1	3	2	4	5	1	2	24
Male	1	1	2	5	5	4	4	8	4	8	8	50

Region of Enrollment
Region of Enrollment(participants)	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
United Kingdom	0	0	0	0	0	0	0	3	9	9	8	29
Switzerland	3	3	3	6	6	7	6	9	0	0	2	45

Study locations

2 sites

Covance Basel Research Unit AG - Lettenweg 118 -
Allschwil, CH - 4123, Switzerland
COVANCE CLINICAL RESEARCH UNIT Ltd - Springfield House - Hyde Street
Leeds, LS2 9LH, United Kingdom

References and documents

Publications

Apfel SC, Kessler JA, Adornato BT, Litchy WJ, Sanders C, Rask CA. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF Study Group. Neurology. 1998 Sep;51(3):695-702. doi: 10.1212/wnl.51.3.695. PubMed 9748012 ↗
Apfel SC, Schwartz S, Adornato BT, Freeman R, Biton V, Rendell M, Vinik A, Giuliani M, Stevens JC, Barbano R, Dyck PJ. Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy: A randomized controlled trial. rhNGF Clinical Investigator Group. JAMA. 2000 Nov 1;284(17):2215-21. doi: 10.1001/jama.284.17.2215. PubMed 11056593 ↗
Bonini S, Lambiase A, Rama P, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology. 2000 Jul;107(7):1347-51; discussion 1351-2. doi: 10.1016/s0161-6420(00)00163-9. PubMed 10889110 ↗
Lambiase A, Rama P, Bonini S, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for corneal neurotrophic ulcers. N Engl J Med. 1998 Apr 23;338(17):1174-80. doi: 10.1056/NEJM199804233381702. PubMed 9554857 ↗
Liu Q, McDermott AM, Miller WL. Elevated nerve growth factor in dry eye associated with established contact lens wear. Eye Contact Lens. 2009 Sep;35(5):232-7. doi: 10.1097/ICL.0b013e3181b3e87f. PubMed 19672199 ↗
Petty BG, Cornblath DR, Adornato BT, Chaudhry V, Flexner C, Wachsman M, Sinicropi D, Burton LE, Peroutka SJ. The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol. 1994 Aug;36(2):244-6. doi: 10.1002/ana.410360221. PubMed 8053664 ↗
Qi H, Li DQ, Shine HD, Chen Z, Yoon KC, Jones DB, Pflugfelder SC. Nerve growth factor and its receptor TrkA serve as potential markers for human corneal epithelial progenitor cells. Exp Eye Res. 2008 Jan;86(1):34-40. doi: 10.1016/j.exer.2007.09.003. Epub 2007 Sep 15. PubMed 17980361 ↗
Schifitto G, Yiannoutsos C, Simpson DM, Adornato BT, Singer EJ, Hollander H, Marra CM, Rubin M, Cohen BA, Tucker T, Koralnik IJ, Katzenstein D, Haidich B, Smith ME, Shriver S, Millar L, Clifford DB, McArthur JC; AIDS Clinical Trials Group Team 291. Long-term treatment with recombinant nerve growth factor for HIV-associated sensory neuropathy. Neurology. 2001 Oct 9;57(7):1313-6. doi: 10.1212/wnl.57.7.1313. PubMed 11591856 ↗
Ferrari MP, Mantelli F, Sacchetti M, Antonangeli MI, Cattani F, D'Anniballe G, Sinigaglia F, Ruffini PA, Lambiase A. Safety and pharmacokinetics of escalating doses of human recombinant nerve growth factor eye drops in a double-masked, randomized clinical trial. BioDrugs. 2014 Jun;28(3):275-83. doi: 10.1007/s40259-013-0079-5. PubMed 24327173 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 19, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01744704
Lead sponsor: Dompé Farmaceutici S.p.A
Collaborators: Covance
Responsible party: Sponsor
First posted: Dec 7, 2012
Start date: Jul 2012
Primary completion: Feb 2013
Completion: Mar 2013
Results posted: Sep 9, 2019
Last update: Apr 19, 2024

Study contacts

Thierry Kamtchoua, MD

principal investigator · Covance Basel Research Unit AG

Ashley Brooks, MBChB

principal investigator · Covance

Pier Adelchi Ruffini, MD

study director · Dompé s.p.a.Via San Martino, 12 - 20122 Milan, Italy

Mauro P Ferrari, PharmD

study director · Dompé s.p.a. - Via San Martino, 12 - 20122 Milan, Italy

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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