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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dompé s.p.a.
ClinicalTrials.gov Identifier:
NCT01744704
First received: December 5, 2012
Last updated: May 20, 2013
Last verified: May 2013
  Purpose

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 Intervention Phase
Healthy
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 20 µg/mL Part B cohort 0M
Drug: rhNGF 60 µg/mL Part B
Drug: rhNGF 180 µg/mL Part B
Drug: Placebo Part A
Drug: Placebo Part B
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Phase I, Randomised, Double-masked, Placebo-controlled, Combined Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Recombinant Human Nerve Growth Factor Eye Drops in Healthy Male and Female Volunteers

Resource links provided by NLM:


Further study details as provided by Dompé s.p.a.:

Primary Outcome Measures:
  • Change in local ocular tolerability score from screening to Day -1, Day 1, Day 3, Day 5, Day 7, Day 10, Day 15 [ Time Frame: Screening, Day -1, Day 1, Day 3, Day 5, Day 7, Day 10, Day 15 ] [ Designated as safety issue: Yes ]
    A global ocular discomfort score will be determined using a 100 mm visual analogue scale (VAS) on which 0 means no symptoms and 100 means the worst possible discomfort. This evaluation is to be performed before any ophthalmic assessment at a given study visit. Specific ocular symptoms to be assessed with the VAS include:foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision,photophobia Part 0: VAS evaluated on days -1, 1, 3, 10 Part A: VAS evaluated on days -1, 1, 3, 10 Part B: VAS evaluated on days -1, 1, 5, 7, 15

  • Change in slit lamp examination (SLE) from screening to Day -1, Day 1, Day 3, Day 5, Day 7, Day 10, Day 15 [ Time Frame: Screening, Day -1, Day 1, Day 3, Day 5, Day 7, Day 10, Day 15 ] [ Designated as safety issue: Yes ]
    Slit lamp examination (SLE) 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) and tear film break-up time Outcome: normal/abnormal Part 0: evaluation at screening and on days -1, 1, 3, 10 Part A: evaluation at screening and on days -1, 1, 3, 10 Part B: evaluation at screening and on days -1, 1, 5, 7, 15

  • Change in intraocular Pressure from screening to Day 3, Day 7, Day 10, Day 15 [ Time Frame: Screening, Day 3, Day 7, Day 10, Day 15 ] [ Designated as safety issue: Yes ]
    Intraocular pressure determination using Goldmann applanation tonometry Outcome: normal/abnormal Part 0: evaluation at screening and on days 3, 10 Part A: evaluation at screening and on days 3, 10 Part B: evaluation at screening and on days 7, 15

  • Change in best corrected distance visual acuity (BCDVA) from screening to Day -1, Day 1, Day 3, Day 5, Day 7, Day 10, Day 15 [ Time Frame: Screening, Day -1, Day 1, Day 3, Day 5, Day 7, Day 10, Day 15 ] [ Designated as safety issue: Yes ]
    Best corrected distance visual acuity measured using the ETDRS (Early Treatment Diabetic Retinopathy Study) score Outcome: normal/abnormal Part 0: BCDVA evaluated at screening and on days -1, 1, 3, 10 Part A: BCDVA evaluated at screening and on days -1, 1, 3, 10 Part B: BCDVA evaluated at screening and on days -1, 1, 5, 7, 15

  • Change in dilated fundus ophthalmoscopy from screening to Day 1, Day 3, Day 5, Day 7, Day 10, Day 15 [ Time Frame: Screening, Day 1, Day 3, Day 5, Day 7, Day 10, Day 15 ] [ Designated as safety issue: Yes ]
    Dilated fundus ophthalmoscopy to assess the vitreous, retina/macula/choroid, and optic nerve, including cup/disc ratio Outcome: normal/abnormal Part 0: evaluation at screening and on days 1, 3, 10 Part A: evaluation at screening and on days 1, 3, 10 Part B: evaluation at screening and on days 1, 5, 7, 15


Enrollment: 74
Study Start Date: July 2012
Study Completion Date: March 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 9 subject
Drug: rhNGF 20 µg/mL Part B
Experimental: rhNGF 20 µg/mL Part B cohort 0M
3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 3 subjects
Drug: rhNGF 20 µg/mL Part B cohort 0M
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01744704

Locations
Switzerland
Covance Basel Research Unit AG - Lettenweg 118 -
Allschwil, Switzerland, CH - 4123
United Kingdom
COVANCE CLINICAL RESEARCH UNIT Ltd - Springfield House - Hyde Street
Leeds, United Kingdom, LS2 9LH
Sponsors and Collaborators
Dompé s.p.a.
Investigators
Principal Investigator: Thierry Kamtchoua, MD Covance Basel Research Unit AG - Lettenweg 118 - CH - 4123 Allschwil / Switzerland
Principal Investigator: Ashley Brooks, MBChB COVANCE CLINICAL RESEARCH UNIT Ltd - Springfield House - Hyde Street - Leeds - LS2 9LH - UK
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
  More Information

Publications:

Responsible Party: Dompé s.p.a.
ClinicalTrials.gov Identifier: NCT01744704     History of Changes
Other Study ID Numbers: NGF0112, 2012-004302-10
Study First Received: December 5, 2012
Last Updated: May 20, 2013
Health Authority: Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Dompé s.p.a.:
Nerve Growth Factor
Ophthalmic Solutions
Eye Drops
rh-NGF

Additional relevant MeSH terms:
Tetrahydrozoline
Mitogens
Nasal Decongestants
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Respiratory System Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014