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HealthyPhase 1NGF0112NCT01744704

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

A Phase 1 study testing rhNGF 0.5 µg/mL Sentinel, rhNGF 5 µg/mL Sentinel and rhNGF 20 µg/mL Sentinel in people with Healthy, run by Dompé Farmaceutici S.p.A at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
rhNGF 0.5 µg/mL Sentinel, rhNGF 5 µg/mL Sentinel and rhNGF 20 µg/mL Sentinel
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
74 participants
Where
2 sitesin 2 countries
Study dates
Jul 2012to Mar 2013
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • Subject must be considered in good systemic health in the opinion of the investigator at the Screening and Baseline visits, as determined by:
  • Subject's body mass index is between 18.5 and 30.4 kg/m2 inclusive
  • A pre-study physical examination with no clinically significant abnormalities.
  • 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).
  • An ECG with no clinically significant abnormalities, in the opinion of the Investigator.
  • 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.

Who cannot join

  • 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:
  • amiodarone and hydroxychloroquine (210 days),
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  • monoclonal antibodies/ immunoglobulins/ other therapeutic proteins (120 days)
  • Experimental drugs with a half life known to the Study Unit: Five half lives plus 2 weeks
  • Experimental drugs with a half life unknown to the Study Unit: 120 days
  • chloroquine and flunarizine (100 days)
  • fluoxetine (75 days),
  • 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

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Switzerland1 site
  • Covance Basel Research Unit AG - Lettenweg 118 -

    Allschwil, CH - 4123

Other trials in Switzerland

United Kingdom1 site
  • COVANCE CLINICAL RESEARCH UNIT Ltd - Springfield House - Hyde Street

    Leeds, LS2 9LH

Other trials in United Kingdom

About this study

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

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
Healthy
Being tested
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
Keywords
Nerve Growth Factor, Ophthalmic Solutions, Eye Drops, rh-NGF
Medical subject headings
Hereditary Sensory and Autonomic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rhNGF 0.5 µg/mL SentinelDrug

    Also called Recombinant Human Nerve Growth Factor

    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

  • rhNGF 5 µg/mL SentinelDrug

    Also called Recombinant Human Nerve Growth Factor

    Part 0 represented a sentinel group.

  • rhNGF 20 µg/mL SentinelDrug

    Also called Recombinant Human Nerve Growth Factor

    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

  • rhNGF 20 µg/mL Part ADrug

    Also called Recombinant Human Nerve Growth Factor

    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.

  • rhNGF 60 µg/mL Part ADrug

    Also called Recombinant Human Nerve Growth Factor

    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.

  • rhNGF 180 µg/mL Part ADrug

    Also called Recombinant Human Nerve Growth Factor

    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.

  • rhNGF 20 µg/mL Part BDrug

    Also called Recombinant Human Nerve Growth Factor

    In Part B, as planned 3 dose levels of rh-NGF or placebo eye drops were studied in a total of 40 healthy subjects.

  • rhNGF 60 µg/mL Part BDrug

    Also called Recombinant Human Nerve Growth Factor

    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.

  • rhNGF 180 µg/mL Part BDrug

    Also called Recombinant Human Nerve Growth Factor

    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.

  • Placebo Part ADrug

    Also called Vehicle

    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.

  • Placebo Part BDrug

    Also called Vehicle

    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.

Study groups in NCT01744704
Study groupRoleWhat they receive
rhNGF 0.5 µg/mL SentinelExperimental1 x 35 µL drop 3 subjects
Receives: Drug: rhNGF 0.5 µg/mL Sentinel
rhNGF 5 µg/mL SentinelExperimental1 x 35 µL drop 3 subjects
Receives: Drug: rhNGF 5 µg/mL Sentinel
rhNGF 60 µg/mL Part AExperimental3 x 35 µL drops applied at 4 h intervals 6 subjects
Receives: Drug: rhNGF 60 µg/mL Part A
rhNGF 20 µg/mL SentinelExperimental1 x 35 µL drop 3 subjects
Receives: Drug: rhNGF 20 µg/mL Sentinel
rhNGF 20 µg/mL Part AExperimental3 x 35 µL drops applied at 4 h intervals 6 subjects
Receives: Drug: rhNGF 20 µg/mL Part A
rhNGF 180 µg/mL Part AExperimental3 x 35 µL drops applied at 4 h intervals 6 subjects
Receives: Drug: rhNGF 180 µg/mL Part A
Placebo Part APlacebo comparator3 x 35 µL drops applied at 4 h intervals 6 subjects
Receives: Drug: Placebo Part A
rhNGF 20 µg/mL Part BExperimental3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 12 subjects
Receives: Drug: rhNGF 20 µg/mL Part B
rhNGF 60 µg/mL Part BExperimental3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects
Receives: Drug: rhNGF 60 µg/mL Part B
rhNGF 180 µg/mL Part BExperimental3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 9 subjects
Receives: Drug: rhNGF 180 µg/mL Part B
Placebo Part BPlacebo comparator3 x 35 µL drops applied at 4 h intervals per day during 5 consecutive days 10 subjects
Receives: Drug: Placebo Part B

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day -1, Day 1, Day 5, Day 15 (FU)

  2. 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.

    Measured: Day -1, Day 1, Day 5, Day 15 (FU)

  3. 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.

    Measured: Day -1, Day 1, Day 5, Day 15 (FU)

  4. 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).

    Measured: Day -1, Day 1, Day 5, Day 15 (FU)

  5. 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.

    Measured: Screening, Day 7, Day 15 (FU)

  6. 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.

    Measured: Part B - Day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionFeb 2013
  4. Study completionMar 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
74 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01744704
Sponsor's protocol ID
NGF0112
Other IDs
2012-004302-10
Acronym
NGF0112
Status last verified
Dec 2023
First submitted
5 Dec 2012
Last updated
19 Apr 2024
Data monitoring committee
No

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rhNGF 0.5 µg/mL Sentinel, rhNGF 5 µg/mL Sentinel and rhNGF 20 µg/mL Sentinel in people with Healthy, run by Dompé Farmaceutici S.p.A at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Switzerland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in VAS Ocular Tolerability (time frame: Day -1, Day 1, Day 5, Day 15 (FU)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01744704, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2024.

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