Safety and Efficacy of rhNGF Eye Drops at Different Doses in Patients With Dry Eye

NCT02101281 | Completed Phase 2 Results

• 2 other identifiers: NGF02132013-004271-12
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study was to assess the efficacy and safety of different doses of rhNGF when administered as eye drops to patients with dry eye.

Conditions

Dry Eye Syndrome

Keywords

Dry Eye

Outcome Measures

Primary Outcomes (5)

• Change From Baseline in Frequency of Dry Eye Symptoms (SANDE)

  The SANDE is a short questionnaire to evaluate the frequency of ocular dryness and/or irritation symptoms. For the assessment, the patients mark on a 100 mm Visual Analogue Scale (VAS) line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patient marks. The SANDE scores (0-100) will be then evaluated for frequency per day.

  Baseline, Day 1, Day 8, Day 29 and Day 56

• Change From Baseline in Severity of Dry Eye Symptoms (SANDE)

  The SANDE is a short questionnaire to evaluate the severity of ocular dryness and/or irritation symptoms. For the assessment, the patients mark on the 100 mm VAS line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimetres from the left-hand end of the line to the point that the patient marks. The SANDE scores (0-100) will be then evaluated for severity. The higher the score, the worse the outcome.

  Baseline, Day 1, Day 8, Day 29 and Day 56

• Change From Baseline in Ocular Surface Vital Staining (National Eye Institute [NEI] Scale)

  The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal score of 15. Both nasally and temporally, the conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 and with a maximal score of 9 for the nasal and temporal conjunctiva. Staining was derived as the sum of scores in the various sectors. The higher the total score the more compromised is the ocular surface.

  Baseline, Day 1, Day 8, Day 29 and Day 56

• Change From Baseline in Tear Wetting Distance as Determined by Schirmer Tear Test I - Study Eye

  The Schirmer test type I (without anaesthesia) was performed to measure aqueous tear secretion prior to the instillation of any dilating or anaesthetic eye drops. The rounded tip of a standardized paper strip is inserted into the lower fornix of the eye, and the wetted length extending out from the lower lid is recorded after 5 min of eye closure. Both eyes could be tested at the same time. Changes from baseline in values of Schirmer's test type I are summarised by eye and evaluation visit, and stratified by severity level. The longer the wetted length the healthier the status of the eye. Only study eye's results are reported hereunder.

  Baseline, Day 1, Day 8, Day 29 and Day 56

• Number of Participants With Treatment-emergent Adverse Events (TEAEs),

  The treatment-emergent adverse events were recorded throughout the whole study.

  Throughout the study up to day 56

Secondary Outcomes (13)

• Change From Baseline in Ocular Tolerability (Visual Analogue Scale, VAS)

  Baseline, Day 1, Day 8, Day 29 and Day 56

• Change From Baseline in Slit Lamp Examination

  Baseline, Day 1, Day 8, Da 29 and Day 56

• Change From Baseline in Tear Wetting Distance as Determined by Schirmer Tear Test II - Study Eye

  Baseline, Day 1, Day 8, Day 29 and Day 56

• Change From Baseline in Tear Film Break-Up Time (TFBUT)

  Baseline, Day 1, Day 8, Day 29 and Day 56

• Change From Baseline in Corneal Fluorescein Staining

  Baseline, Day 1, Day 8, Day 29 and Day 56

Study Arms (2)

Group 1 - rhNGF 20 μg/mL

EXPERIMENTAL

(first planned dose): drop (35 μL) corresponding to 0.70 μg of rhNGF (recombinant human Nerve Growth Factor) was instilled into each eye twice a day (b.i.d.) every 12±2 h for a total daily dose of 2.8 μg (both eyes), for 28 consecutive days. The total dose was 78.4 μg/28 days.

Drug: rhNGF 20 µg/mL

Group 2 - rhNGF 4 μg/mL

EXPERIMENTAL

after completion of Group 1 treatment, one drop (35 μL) corresponding to 0.14 μg of rhNGF (recombinant human Nerve Growth Factor) instilled into each eye b.i.d. every 12±2 h for a total daily dose of 0.56 μg, for 28 consecutive days. Total dose was 15.68 μg/28 days.

Drug: rhNGF 4 µg/mL

Interventions

rhNGF 20 µg/mL DRUG

1 drop for each eye, twice daily for 28 day

Also known as: cenegermin, recombinant human Nerve Growth Factor

Group 1 - rhNGF 20 μg/mL

rhNGF 4 µg/mL DRUG

1 drop each eye, twice daily for 28 day

Also known as: cenegermin, recombinant human Nerve Growth Factor

Group 2 - rhNGF 4 μg/mL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, ≥ 18 years old;
• Required use of artificial tears for the treatment of Dry Eye within the 3 months prior to study enrolment;
• Current use or recommended use of artificial tears for the treatment of Dry Eye;
• Average VAS score for typical symptoms of Dry Eye (foreign body sensation, burning/stinging, itching, pain, stick feeling, blurred vision and photophobia) ≥ 25 mm;
• Corneal staining score with lissamine green \> 3 using the NEI corneal grading system in the worse eye (study eye);
• Conjunctival staining score \> 3 using the NEI conjunctival grading system in the worse eye (study eye);
• Schirmer test without anaesthesia ≤ 10 mm/5 minutes in the worse eye (study eye);
• Tear film break-up time (TBUT) ≤ 10 seconds in the worse eye (study eye);
• A negative urine pregnancy test if female of childbearing potential and must use adequate birth control throughout the study period

You may not qualify if:

• Patient not suitable to participate in the study in the opinion of the investigator;
• Patient with a mild or moderate Dry Eye condition (severity level less than 3 according to the Report of the International Dry Eye Workshop -DEWS, 2007) if fourteen (14) patients with mild or moderate dry eye condition have been already enrolled in the current treatment group (Group 1 and Group 2 separately);
• Patient 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, amide local anaesthetics or other materials including commercial artificial tears containing Hypromellose (in the opinion of the investigator);
• Use of topical cyclosporine, topical corticosteroids or any other topical medication for the treatment of dry eye in either eye within 30 days of study enrolment. Use of own artificial tears is allowed until Visit 2;
• Any ocular disease other than Dry Eye requiring treatment with topical medications in either eye within 30 days of study enrolment;
• Any active ocular infection or active inflammation in either eye unrelated to Dry Eye;
• Presence or history of any systemic or ocular disorder, condition or disease that could possibly interfere with the conduct of the required study procedures or the interpretation of the study results;
• Use of therapeutic or Refractive Contact lenses in either eye within 30 days of study enrolment;
• History of ocular surgery in the study eye, including corneal refractive procedures, within 90 days of study enrolment;
• Participation in another clinical study at the same time as the present and within 30 days of study enrolment;
• History of drug, medication or alcohol abuse or addiction.

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead
• Cross Research S.A.: collaborator

Study Sites (1)

Department of Clinical Pharmacology

Vienna, 1090, Austria

Location

Related Publications (1)

• Sacchetti M, Lambiase A, Schmidl D, Schmetterer L, Ferrari M, Mantelli F, Allegretti M, Garhoefer G. Effect of recombinant human nerve growth factor eye drops in patients with dry eye: a phase IIa, open label, multiple-dose study. Br J Ophthalmol. 2020 Jan;104(1):127-135. doi: 10.1136/bjophthalmol-2018-312470. Epub 2019 Apr 3.

  PMID: 30944103 DERIVED

MeSH Terms

Conditions

Dry Eye Syndromes

Interventions

cenegermin

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Limitations and Caveats

LImitations and caveats non specified

Results Point of Contact

• Title: Flavio Mantelli, MD, PhD
• Organization: Dompé

info@dompe.it

+39 513138

Study Officials

• Gerhard Garhöfer, MD

  Medical University of Vienna, Vienna General Hospital, AKH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: April 2, 2014
• Study Start: January 20, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: April 19, 2024
• Results First Posted: August 7, 2019

Record last verified: 2022-12

Locations

AU (1)