Efficacy and Safety of Plasma Rich in Growth Factors (PRGF-Endoret) Eye-drops in the Treatment of Neurotrophic Keratitis

Randomized, Parallel Groups, Multicenter and Blind to Evaluators Clinical Trial, to Evaluate the Efficacy and Safety of PRGF-Endoret Eye Drops, in Patients With Stage 2 and 3 Neurotrophic Keratitis

Neurotrophic keratitis (NK) is a rare degenerative corneal disease caused by altered innervation of the trigeminal nerve that leads to rupture of the corneal epithelium, the regeneration deterioration and development of corneal ulceration, their fusion, and perforation The main characteristic in the NK is a decrease or absence of corneal sensitivity.

Study Overview

• Status: Unknown
• Conditions: Neurotrophic Keratitis
• Intervention / Treatment: Drug: PRGF-Endoret; Drug: Artificial tears eye-drops

Detailed Description

The goals of treatment in the neurotrophic keratitis are prevent the progression of corneal damage, maintain eye structure and improve the transparency of the cornea. Therapy should be initiated early and based on the clinical stage of the disease because it depends on epithelial state and in the degree of corneal hypoesthesia.

Plasma rich in growth factors (PRGF-Endoret) represent a new technology using autologous proteins, growth factors and biomaterials as therapeutic formulations for different regenerative purposes. Under strict pharmaceutical development, it is possible to develop biologically stable eye drops, which have been shown to be useful for treating diverse ocular surface diseases. PRGF-Endoret eye drops could be an alternative therapy for patients with NK, and thus the objective of this clinical trial is to demonstrate its possible efficacy and its safety in patients with NK in stages 2 and 3.

• Study Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gorka Orive, PhD; Phone Number: 663027696; Email: gorka.orive@bti-implant.es

Study Locations

• Spain
  • Barcelona, Spain
    • Instituto de Microcirugía Ocular (IMO)
  • Madrid, Spain
    • Hospital Ramón y Cajal
  • Asturias
    • Oviedo, Asturias, Spain
      • Instituto Oftalmologico Fernandez-Vega
  • Bizkaia
    • Bilbao, Bizkaia, Spain
      • Instituto Clínico Quirúrgico de Oftalmología (ICQO)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged 18 or over.
• With neurotrophic keratitis at stages 2 or 3 affecting only one eye.
• Persistent epithelial defect or corneal ulcer of at least 2 weeks duration resistant to one or more traditional non-surgical treatments .
• Corneal sensitivity reduction test in the area of the persistent epithelial defect or corneal ulcer and out of the defect area in at least one corneal quadrant.
• No objective clinical evidence of improvement in the two weeks prior to enrollment.
• Patients who have previously read and signed the informed consent.

Exclusion Criteria:

• Patients with neurotrophic keratitis stages 2 or 3 that affects both eyes.
• With active ocular infection or inflammation not related to the neurotrophic keratitis
• Any other eye disease that requires of topical ocular treatment in the affected eye during study.
• Patients with severe vision loss
• Patients with severe blepharitis and/or severe Meibomian glands disease
• History of eye surgery in the three months prior to enter the study, or patients who plan to undergo surgery.
• Having received previously surgical procedures for the treatment of NK.
• Use of therapeutic contact lenses or for refractive correction during study.
• Patients with punctual occlusion or insertion of punctual plugs previous to the study
• Evidence of corneal ulcer affecting the corneal stroma or cornea perforation.
• Presence of any disorder or ocular or systemic disease that could limit the treatment effectiveness or its evaluation,
• Any need of change (at that time or planned) in the dose of systemic drugs known to disrupt the functioning of the trigeminal nerve
• Known hypersensitivity to any of the procedural compounds (eg. fluoresceine).
• Presence of blood disorders associated with platelet disorders or clotting, or receiving anticoagulants drugs or antiplatelet agents.
• Patients with positive result in one of the serological tests for syphilis, Hepatitis B-C or AIDS I / II.
• Patient in current treatment for their pathology already well managed.
• Use of any investigational drug within 4 weeks prior to the screening visit.
• Pregnant women or intended to be pregnant.
• Participating in another clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRGF-Endoret eye-drops	Drug: PRGF-Endoret; Active treatment will be PRP eye drops obtained by the PRGF-Endoret system.
Active Comparator: Artificial tears eye-drops	Drug: Artificial tears eye-drops; Artificial tear moisturizing eyedrops (Hidrathea®, Nacl 0.9 % solution without preservatives).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with a reduction of corneal defect of >50%	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with a reduction of corneal defect of >50%		2 weeks
Percentage of patients showing complete healing of the corneal defect		4 weeks
Percentage of patients showing complete healing of the corneal defect		2 weeks
Measurement of the depth of the corneal defect (mm)		2 and 4 weeks
Changes in percentage in Best corrected visual acuity (BCVA LogMAR)		2 and 4 weeks
Ocular pain with VAS scale		2 and 4 weeks
Osmolarity of lacrimal film		2 and 4 weeks
Measurement of treatment tolerance	Measurement of treatment tolerance with a 0 4 score	2 and 4 weeks
Adverse events	Percentage of adverse event occurrence	2 and 4 weeks

Collaborators and Investigators

• Sponsor: Biotechnology Institute IMASD

Study record dates

Study Major Dates

• Study Start (Anticipated): January 4, 2018
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: February 29, 2016
• First Submitted That Met QC Criteria: March 11, 2016
• First Posted (Estimate): March 14, 2016

Study Record Updates

• Last Update Posted (Actual): July 14, 2017
• Last Update Submitted That Met QC Criteria: July 12, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: PRGF, Neurotrophic Keratitis, platelet rich plasma, PRP
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratitis; Pharmaceutical Solutions; Ophthalmic Solutions; Lubricant Eye Drops
• Other Study ID Numbers: BTI-011-EC/15/QUER

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No