This is a phase I/II prospective, randomized, multi-center, double-masked, vehicle-controlled clinical trial evaluating the safety and efficacy of corneal collagen cross-linking the keratoprosthesis carrier tissue in subjects who are candidates for high-risk keratoprosthesis implantation but because of a history of corneal melts or autoimmune diseases are not candidate for a traditional corneal transplant.
Full Title of Study: “A Phase I/II Prospective, Randomized, Multicenter, Double-Masked, Vehicle-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Corneal Collagen Cross-Linking of Keratoprosthesis Carrier Tissue in High-Risk Keratoprosthesis Implantation”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Prevention
- Masking: Double (Participant, Investigator)
- Study Primary Completion Date: June 2021
The study is a multi-center, parallel, randomized, double-blinded study with subsequent follow-up period of two years. Eight-four subjects across twelve sites will be randomized 1:1 to receive either a corneal tissue that have been cross-linked or not cross-linked (No UVA light source). Cross-linking is a term that refers to the linking of polymers (long chain) molecules by chemical bonds. It is believed that cross-linking the cornea will make the cornea stronger and more resistant to degradation. CorneaGen (formerly Keralink International) (Baltimore site) will supply the donor tissue and Avedro Inc (Waltham MA) will supply the riboflavin and the UV light source. Staff at CorneaGenwill administer the riboflavin with dextran solution and perform the cross-linking procedure according to one of randomization groups before shipping the masked donor cornea to study sites for Boston Keratoprosthesis (B-KPro) implantation.
- Drug: Riboflavin
- Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods.
- Drug: Dextran
- Dextran is used to increase the viscosity of the solution.
- Device: UVA Light Source
- Avedro’s KXL® System is a UVA irradiation system that uses a light emitting diode (LED) to deliver a dose of UVA light to a targeted treatment area for illuminating the cornea during corneal collagen cross-linking.
Arms, Groups and Cohorts
- Experimental: Active Treatment Arm
- De-epithelialized corneas cross-linked with riboflavin 0.1% and dextran 20% solution AND ultraviolet A light (UVA Light Source).
- Active Comparator: Control Treatment Arm
- De-epithelialized corneas will be exposed to only riboflavin 0.1% with dextran 20% solution (NO ultraviolet A light).
Clinical Trial Outcome Measures
- Time from surgery to device loss or replacement
- Time Frame: 2 years
- If the device fails after surgery the time and reason behind the failure will be recorded. The number of device losses in the control group will be compared to the number of device losses in investigational group.
- Twelve-month retention rate
- Time Frame: Twelve months
- The number of retained devices at the end of twelve months will be studied and differences in retention rate between investigational and control groups will be reported
- Incidence of delayed epithelial healing at day 7
- Time Frame: 7 days
- The incidences of delayed epithelial healing at day 7 will be recorded. If there is delayed epithelial healing at day 7 it will be determined if those incidences occurred more often in the control group versus the investigational group.
- Cornea thickness metrics measured by AS-OCT; at week(s) 1, 4, 16, 24, 36, 52, 78, and 104.
- Time Frame: week(s) 1, 4, 16, 24, 36, 52, 78, and 104
- Cornea thickness will be measured before and after study intervention and at all follow up visits. Corneal thickness will be analyzed and occurrences will be recorded to compare between study groups.
- Time from surgery to retroprosthetic membrane treatment (laser or surgical interventions)
- Time Frame: 2 years
- If follow up surgery is needed to replace or treat the prosthetic the time and reason will be recorded and these incidences will be compared between the study treatment groups
- Time from surgery to occurrence of vitritis (sterile or infectious)
- Time Frame: 2 years
- The incidences of vitritis will be recorded and the number of incidences will be compared between the study treatment groups. The timing of these incidences will also be recorded.
Participating in This Clinical Trial
- Willing and able to provide written informed consent – Willing and able to comply with study assessments for the full duration of the study – Age ≥ 18 years – Candidate for a Boston Keratoprosthesis / Cornea transplant – In generally good stable overall health – Patients with an eye at risk for a cornea sterile ulcer which includes: – Autoimmune diseases (mucus membrane pemphigoid, Stevens-Johnson syndrome, systemic lupus erythematosis, rheumatoid arthritis, or other autoimmune diseases); OR – History of previous sterile cornea ulceration requiring a cornea transplant Exclusion Criteria:
- Age < 18 years – Inability to provide written informed consent and comply with study assessments for the full duration of the study – No or minimal tear production with evidence of keratinization of the bulbar conjunctiva – Corneal or ocular surface infection within 30 days prior to study entry – Ocular or periocular malignancy – Inability to wear a contact lens due to lid abnormalities or shortened fornix – Signs of current infection, including fever and current treatment with antibiotics – Pregnancy (positive pregnancy test) or lactating – Participation in another simultaneous interventional medical investigation or trial
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Joseph B. Ciolino, MD
- United States Department of Defense
- Provider of Information About this Clinical Study
- Sponsor-Investigator: Joseph B. Ciolino, MD, Professor of Opthalmology – Massachusetts Eye and Ear Infirmary
- Overall Official(s)
- Joseph B. Ciolino, MD, Principal Investigator, Massachusetts Eye and Ear Infirmary
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