Use of a Freeze-dried Amniotic Membrane Post Crosslinking in Subjects With Progressive Keratoconus

Multicenter, Randomized Study Evaluating the Use of a Non-sutured Sterile Freeze-dried Amniotic Membrane Post Crosslinking in Subjects With Progressive Keratoconus

Crosslinking is a therapeutic technique used to increase the rigidity of the cornea in order to slow or stop progression of keratoconus. The main complication of the treatment of keratoconus by crosslinking is postoperative pain due to the removal of the corneal epithelium. Currently, the management of pain is done through the administration of artificial tears and paracetamol. The amniotic membrane is a biological tissue used in ophthalmology to treat injuries of the surface of the eye. It has healing and analgesic properties.

The objective of this multicenter randomized study is to evaluate the benefit of placing an amniotic membrane on the eye post-crosslinking to reduce pain and promote corneal healing.

Study Overview

• Status: Recruiting
• Conditions: Progressive Keratoconus
• Intervention / Treatment: Device: Therapeutic lens alone; Combination product: Therapeutic lens + amniotic membrane (Visio-AMTRIX)

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Justine BOSC, MSc; Phone Number: +33 4 72 68 69 11; Email: justine.bosc@tbf-lab.com
• Study Contact Backup: Name: Laurence BARNOUIN, MD; Phone Number: +33 0472686909; Email: laurence.barnouin@tbf-lab.com

Study Locations

• France
  • Brest, France, 29609
    • Recruiting
    • CHU de Brest
    • Contact: Béatrice COCHENER-LAMARD, Professor
  • Lyon, France, 69003
    • Recruiting
    • Hospices Civils de Lyon
    • Contact: Carole BURILLON, Professor
  • Marseille, France, 13005
    • Recruiting
    • Assistance Publique - Hopitaux de Marseille
    • Contact: Thierry DAVID, Professor
  • Montpellier, France, 34295
    • Recruiting
    • CHU de Montpellier
    • Contact: Vincent DAIEN, Professor
  • Nantes, France, 44000
    • Not yet recruiting
    • CHU de Nantes
    • Contact: Isabelle ORIGNAC, MD
  • Paris, France, 75012
    • Recruiting
    • Hôpital National de la Vision des Quinze-Vingts
    • Contact: Juliette KNOERI, MD
    • Contact: Vincent BORDERIE, Professor
  • Saint-Priest-en-Jarez, France, 42270
    • Recruiting
    • Chu de Saint-Etienne
    • Contact: Marie-Caroline TRONE, MD
  • Strasbourg, France, 67000
    • Recruiting
    • Hopitaux universitaires de Strasbourg
    • Contact: Tristan BOURCIER, Professor
  • Toulouse, France, 31300
    • Recruiting
    • CHU de Toulouse
    • Contact: Pierre FOURNIÉ, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Man or woman between 18 and 65 years old.
• Indication for accelerated conventional crosslinking.
• Patient with progressive keratoconus (increase in Kmax of ≥ 0.5 diopters in 3 to 6 months or ≥ 1 diopter in 3 to 12 months with loss of 10 microns on minimum pachymetry in 3 to 12 month).
• Patient suffering from keratoconus with a compatible topographic form (Kmax ≥ 47.0 diopters (D) and difference inferior-superior of 1.5 D).
• Patient with a minimum corneal thickness greater than 400 microns.
• Informed and consenting patient.
• Patient physically and mentally capable of completing the post-operative pain assessment self-questionnaire.
• Patient having signed the informed consent of the French Ophthalmology Society for crosslinking.
• Patient affiliated to a social security system or beneficiary of such a system.

Exclusion Criteria:

• Woman without effective means of contraception, pregnant or breastfeeding.
• Patient who has already benefited from a crosslinking procedure on one of the eyes.
• Patient with a history of refractive surgery on one of the eyes.
• Patient with an intracorneal ring segment on one of the eyes.
• Patient suffering from a serious systemic pathology (autoimmune and/or immunodepressive)
• Patient with a psychiatric pathology.
• Patient on long-term analgesics and/or corticosteroids.
• Indication of crosslinking outside the classic protocol.
• Patient with central corneal opacity.
• Patient suffering from a severe dry eye syndrome or a neurotrophic keratitis.
• Patient with a history of ocular herpes.
• Patient with a history of ocular varicella-zoster virus infection.
• Patient with glaucoma.
• Patient treated with topical cyclosporine in the last 6 months.
• Patient deprived of liberty by a judicial or administrative decision.
• Patient subject to a legal protection measure or unable to express their consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Therapeutic lens alone	Device: Therapeutic lens alone; Therapeutic lens will be apposed on the patient's eye after crosslinking. Therapeutic lens will be maintained without interruption until the first postoperative visit (Day 2) when it will be removed by the investigator.
Experimental: Therapeutic lens + amniotic membrane (Visio-AMTRIX)	Combination product: Therapeutic lens + amniotic membrane (Visio-AMTRIX); Amniotic membrane (Visio-AMTRIX) will be apposed under therapeutic lens on the patient's eye after crosslinking. Amniotic membrane and therapeutic lens will be maintained without interruption until the first postoperative visit (Day 2) when it will be removed by the investigator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between the level of ocular pain experienced by patients treated with therapeutic lens + amniotic membrane (experimental) and by patients treated with therapeutic lens alone (active comparator)	Pain evaluated from 0: no pain to 10: worst imaginable pain on visual analog scale (VAS)	Day 0 bedtime, Day 1 wake-up, Day 1 bedtime, Day 2 wake-up, Day 2 consultation
Difference in analgesic consumption between patients treated with a therapeutic lens + amniotic membrane (experimental) and patients treated with a therapeutic lens alone (active comparator)	Amount in grams of analgesic consumed per day	Day 0, Day 1, Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in visual acuity between eyes treated with therapeutic lens + amniotic membrane (experimental) and eyes treated with therapeutic lens alone (active comparator)	Determination of logMAR values of best corrected visual acuity	Week 6
Difference in corneal cicatrisation between eyes treated with therapeutic lens + amniotic membrane (experimental) and eyes treated with therapeutic lens alone (active comparator)	Healing evaluated under slit lamp by fluorescein examination	Day 2, (Day 7), Week 6
Difference in corneal thickness between eyes treated with therapeutic lens + amniotic membrane (experimental) and eyes treated with therapeutic lens alone (active comparator)	Corneal thickness evaluated by anterior segment optical coherence tomography.	Week 6
Difference in topographic parameters (Kmax, inferior-superior) between eyes treated with therapeutic lens + amniotic membrane (experimental) and eyes treated with therapeutic lens alone (active comparator)	Topographic parameters (Kmax, inferior-superior) evaluated by corneal topography	Week 6
Difference in dryness between eyes treated with therapeutic lens + amniotic membrane (experimental) and eyes treated with therapeutic lens alone (active comparator)	Dry eye and effect on vision evaluated between 0 (no disability) and 100 (greater disability) using Ocular Surface Disease Index (OSDI)	Week 6

Collaborators and Investigators

• Sponsor: TBF Genie Tissulaire

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: June 4, 2024
• First Submitted That Met QC Criteria: June 4, 2024
• First Posted (Actual): June 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus
• Other Study ID Numbers: GMALC; 2024-A00004-43 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No