Evaluation of Safety and Efficacy of rhNGF in Patients With Stage 2 and 3 Neurotrophic Keratitis.

NCT01756456 | Completed Phase 1 Results DMC

• 2 other identifiers: NGF02122012-002527-15
• Study Type: interventional
• Target: 174
• Locations: 6 countries
• Sites: 34

Brief Summary

This study is aimed at assessing the safety and the efficacy of two dose regimens of recombinant human nerve growth factor (rhNGF) eye drops solution compared to vehicle for inducing a complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis

Conditions

Neurotrophic Keratitis; Keratitis; Corneal Ulcer

Keywords

Keratitis; Corneal Ulcer

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Achieving Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer

  Complete healing of the PED or corneal ulcer was determined by corneal fluorescein staining at 4 weeks as defined by the reading center evaluating the clinical pictures. Complete healing was defined as the greatest diameter of the corneal fluorescein staining in the area of the PED or corneal ulcer being less than 0.5 mm at the Week 4 visit. The primary efficacy variable was analyzed after 4 weeks of treatment only for the Phase II segment of the study. That's why the Phase I groups/arms are not included in this analysis.

  at 4 weeks of treatment

Secondary Outcomes (12)

• Percentage of Patients Experiencing Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer

  at 4 weeks of study treatment.

• Percentage of Patients Experiencing Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer

  at 6 and 8 weeks after start of the treatment

• Percentage of Patients Experiencing Complete Corneal Clearing

  at 4, 6 and 8 weeks after start of the treatment

• Mean Change in Best Corrected Distance Visual Acuity (BCDVA)

  At screening and at week 8

• Percentage of Patients That Achieve an Improvement in Corneal Sensitivity

  at 4, 6 and 8 weeks.

Other Outcomes (1)

• Percentage of Patients That Achieved a ≥15 Letter Gain in BCDVA

  at 4, 6 and 8 weeks

Study Arms (6)

1_rhNGF10_Phase 1_treatment

EXPERIMENTAL

active treatment with rhNGF 10 μg/ml. One drop six times a day (one 35 μl drop equals to 0.35μg of rhNGF).

Drug: rhNGF 10 μg/ml

2_rhNGF20_Phase 1_treatment

EXPERIMENTAL

active treatment with rhNGF 20 μg/ml. One drop 6 times a day (one 35 μl drop equals to 0.70 μg of rhNGF)

Drug: rhNGF 20 μg/ml

3_vehicle group_Phase 1_treatment

PLACEBO COMPARATOR

vehicle control arm. Ophthalmic solution of the same composition as the test product with the exception of rhNGF. One drop six times a day for the entire period

Other: vehicle

4_rhNGF10_Phase 2_treatment

EXPERIMENTAL

active treatment with rhNGF 10 μg/ml. One drop six times a day (one 35 μl drop equals to 0.35 μg of rhNGF)

Drug: rhNGF 10 μg/ml

5_rhNGF20_Phase 2_treatment

EXPERIMENTAL

active treatment with rhNGF 20 μg/ml. One drop 6 times a day (one 35 μl drop equals to 0.70 μg of rhNGF)

Drug: rhNGF 20 μg/ml

6_vehicle group_Phase 2_treatment

PLACEBO COMPARATOR

vehicle control arm. Ophthalmic solution of the same composition as the test product with the exception of rhNGF. One drop six times a day for the entire period

Other: vehicle

Interventions

rhNGF 10 μg/ml DRUG

rhNGF 10 μg/ml : one drop 6 times a day (one 35 μl drop equals to 0.35 μg of rhNGF)

Also known as: recombinant human nerve growth factor 10 µg/ml solution

1_rhNGF10_Phase 1_treatment; 4_rhNGF10_Phase 2_treatment

rhNGF 20 μg/ml DRUG

one drop 6 times a day (one 35 μl drop equals to 0.70 μg of rhNGF)

Also known as: recombinant human nerve growth factor 20 µg/ml solution

2_rhNGF20_Phase 1_treatment; 5_rhNGF20_Phase 2_treatment

vehicle OTHER

ophthalmic solution of the same composition as the test product without rhNGF

Also known as: placebo

3_vehicle group_Phase 1_treatment; 6_vehicle group_Phase 2_treatment

Eligibility Criteria

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

You may qualify if:

• Patients 18 years of age or older.
• Patients with stage 2 (persistent epithelial defect, PED) or stage 3 (corneal ulcer) neurotrophic keratitis involving only one eye. . Patients with Controlateral eye affected with stage 1 NK can be enrolled.
• PED or corneal ulceration of at least 2 weeks duration refractory to one or more conventional non-surgical treatments for neurotrophic keratitis (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops and medications that can decrease corneal sensitivity; therapeutic contact lenses).
• Evidence of decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant.
• Best corrected distance visual acuity (BCDVA) score ≤ 75 ETDRS letters, (≥ 0.2 LogMAR, ≤ 20/32 Snellen or ≤ 0.625 decimal fraction) in the affected eye.
• No objective clinical evidence of improvement in the PED or corneal ulceration within the 2 weeks prior to study enrolment.
• Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent form signed by patients and/or legal representative must have been approved by the IEC/IRB for the current study.
• Patients must have the ability and willingness to comply with study procedures.
• Patients must be eligible for the National Health Insurance (where applicable).

You may not qualify if:

• Patients with stage 2 or 3 NK affecting both eyes.
• Any active ocular infection (bacterial, viral, fungal or protozoal) or active ocular inflammation not related to NK in the affected eye.
• Any other ocular disease requiring topical ocular treatment in the affected eye during the course of the study treatment period. No topical treatments other than the study medications provided by the study sponsor or allowed by the study protocol can be administered in the affected eye during the course of the study treatment periods.
• Patients with severe vision loss in the affected eye with no potential for visual improvement in the opinion of the investigator as a result of the study treatment.
• Schirmer test without anesthesia ≤3 mm/5 minutes in the affected eye.
• Patients with severe blepharitis and/or severe meibomian gland disease in the affected eye.
• History of any ocular surgery (including laser or refractive surgical procedures) in the affected eye within the three months before study enrolment. (An exception to the preceding statement will be allowed if the ocular surgery is considered to be the cause of the stage 2 or 3 NK). Ocular surgery in the affected eye will not be allowed during the study treatment period and elective ocular surgery procedures should not be planned during the duration of the follow-up period.
• Prior surgical procedure(s) for the treatment of NK (e.g. complete tarsorraphy, conjunctival flap, etc) in the affected eye with the exception of amniotic membrane transplantation. Patients previously treated with amniotic membrane transplantation may only be enrolled two weeks after the membrane has disappeared within the area of the PED or corneal ulcer or at least six weeks after the date of the amniotic membrane transplantation procedure. Patients previously treated with Botox (botulinum toxin) injections used to induce pharmacologic blepharoptosis are eligible for enrolment only if the last injection was given at least 90 days prior to enrolment in the study.
• Use of therapeutic contact lenses or contact lens wear for refractive correction during the study treatment periods in the eye with NK.
• Anticipated need for punctual occlusion during the study treatment period. Patients with punctual occlusion or punctual plugs inserted prior to the study are eligible for enrolment provided that the punctual occlusion is maintained during the study.
• Evidence of corneal ulceration involving the posterior third of the corneal stroma, corneal melting or perforation in the affected eye.
• Presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the investigator to be incompatible with the study visit schedule or conduct (e.g. progressive or degenerative corneal or retinal conditions, uveitis, optic neuritis, poorly controlled diabetes, autoimmune disease, systemic infection, neoplastic diseases).
• Any need for or anticipated change in the dose of systemic medications known to impair the function of the trigeminal nerve (e.g. neuroleptics, antipsychotic and antihistamine drugs). These treatments are allowed during the study if initiated prior to 30 days before study enrolment provided they remain stable throughout the course of the study treatment periods.
• Known hypersensitivity to one of the components of the study or procedural medications (e.g. fluorescein).
• History of drug, medication or alcohol abuse or addiction.

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (34)

CHU de Dijon - Service ophtalmologie

Dijon, 21000, France

Location

CHU Dupuytren - Service Ophtalmologie

Limoges, 87042, France

Location

Centre Hospitalier National d'Ophtalmologie - Service d'ophtalmologie

Paris, 75 571, France

Location

"Fondation Ophtalmologique Adolphe de Rothschild - "Unité de Recherche Clinique

Paris, 75019, France

Location

"CHU Toulouse-Purpan - Service Ophtalmologie

Toulouse, 31059, France

Location

Universität zu Köln - Zentrum für Augenheilkunde am Universitätsklinikum Köln

Cologne, 50924, Germany

Location

University Eye Clinic in Düsseldorf

Düsseldorf, 50924, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Universitäts-Augenklinik Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Johannes-Gutenberg-Universität Augenklinik und Poliklinik - Department of Ophthalmology

Mainz, 55131, Germany

Location

Klinikum der Universität München - Augenklinik der Ludwig-Maximilians-Universtiät München

München, 80336, Germany

Location

OSPEDALE SAN RAFFAELE di Milano

Milan, Lombardy, 20132, Italy

Location

Università G. D' Annunzio - Clinica Oftalmologica - Centro regionale di Eccellenza in Oftalmologia

Chieti, 66100, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50124, Italy

Location

Dipartimento di Scienze Neurologiche Oftalmologia e Genetica - Universtità di Genova

Genoa, 16132, Italy

Location

Azienda Ospedaliero Universitaria di Messina - Dipartimento Specialità Chirurgiche Ambulatorio Studio delle Malattie dela Superficie Oculare Unità Operativa Complessa di Oftalmologia

Messina, 98125, Italy

Location

Azienda Ospedaliera San Paolo - U.O. Oculistica

Milan, 20142, Italy

Location

Azienda ospedaliera di Padova - Clinica Oculistica Policlinico 7° Piano

Padua, 35128, Italy

Location

Università Campus Bio-Medico di Roma

Rome, 00128, Italy

Location

Policlinico Umberto I

Rome, 00161, Italy

Location

District Railway Hospital Katowice - Department of Ophthalmology

Katowice, 40-760, Poland

Location

"SPKSO Szpital Okulistyczny ul. - SPKSO Szpital Okulistyczny

Warsaw, 03-709, Poland

Location

Vissum Corporación Oftalmológica de Alicante

Alicante, 03016, Spain

Location

Hospital de Cruces - Oftalmología

Barakaldo, 48903, Spain

Location

Barraquer Eye center

Barcelona, 08021, Spain

Location

Hospital Clinic de Barcelona - Oftalmología

Barcelona, 08028, Spain

Location

Hospital Clínico San Carlos - Oftalmología. Unidad de Superficie Ocular

Madrid, 28040, Spain

Location

Instituto Oftalmológico Fernández-Vega - Oftalmología

Oviedo, 33012, Spain

Location

Cartuja Visión - Oftalmología

Seville, 41092, Spain

Location

University of Birmingham - Academic Unit of Ophthalmology, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham

Birmingham, "B15 2TT, United Kingdom

Location

Moorfields Eye Hospital - Moorfields Eye Hospital

London, EC1V 2PD, United Kingdom

Location

Manchester Royal Eye Hospital - Manchester Royal Eye Hospital

Manchester, M13 9WL, United Kingdom

Location

Royal Victoria Infirmary - Dept. of Ophthalmology

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

University of Southampton Southampton General Hospital - MP104, Eye Unit

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Yanai R, Nishida T, Chikama T, Morishige N, Yamada N, Sonoda KH. Potential New Modes of Treatment of Neurotrophic Keratopathy. Cornea. 2015 Nov;34 Suppl 11:S121-7. doi: 10.1097/ICO.0000000000000587.

  PMID: 26448169 DERIVED

MeSH Terms

Conditions

Keratitis; Corneal Ulcer

Interventions

cenegermin; Solutions

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases; Eye Infections; Infections

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Limitations and Caveats

None reported

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé farmaceutici s.p.a.

clinical.trials@dompe.com

+39 02 583831

Study Officials

• Francesco Sinigaglia, MD

  Dompé s.p.a., Milan

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2012
• First Posted: December 27, 2012
• Study Start: January 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: May 1, 2016
• Last Updated: April 19, 2024
• Results First Posted: July 29, 2019

Record last verified: 2017-02

Locations

ES (7); DE (6); FR (5); PL (2); GB (5); IT (9)