Keratolysis
Conditions
Keywords
Keratolysis, Corneal Melting, Boston KPro, Keratoprosthesis
Brief summary
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.
Detailed description
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.
Interventions
DRUGRiboflavin
Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods.
DRUGDextran
Dextran is used to increase the viscosity of the solution.
DEVICEUVA 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.
Sponsors
United States Department of Defense
Joseph B. Ciolino, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Surgery to Device Loss or Replacement | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Kpro Retention at 12 Months | Twelve months | The number of participants that retained kpro devices at the end of twelve months will be studied and differences in retention rate between investigational and control groups will be reported |
| Number of Cumulative Delayed Epithelial Healing Events at Day 30 | 30 days | The number of incidences of delayed epithelial healing at day 30 will be recorded. If there is delayed epithelial healing at day 30 it will be determined if those incidences occurred more often in the control group versus the investigational group. |
| Median Time From Surgery to Retroprosthetic Membrane Treatment in Days (Laser or Surgical Interventions) | 2 years | If follow up surgery is needed to replace or treat the prosthetic the time and reason will be recorded and the number of incidences will be compared between the study treatment groups |
| Median Time From Surgery to Occurrence of Vitritis (Sterile or Infectious) | 2 years | The time (days) and number of incidences of vitritis will be recorded for the subject in which it occurred and the number of incidences will be compared between the study treatment groups. |
Countries
United States
Participant flow
Pre-assignment details
76 subjects enrolled - signed consent form * 5 screen fails (did not meet eligibility criteria); * 1 withdrawal (signed consent form but declined to participate before randomization occurred) * 2 other (signed consent forms but were not able to receive surgery due to COVID-19 restrictions)
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment Arm De-epithelialized corneas cross-linked with riboflavin 0.1% and dextran 20% solution AND ultraviolet A light (UVA Light Source).
Riboflavin: Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods.
Dextran: Dextran is used to increase the viscosity of the solution.
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. | 33 |
| Control Treatment Arm De-epithelialized corneas will be exposed to only riboflavin 0.1% with dextran 20% solution (NO ultraviolet A light).
Riboflavin: Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods.
Dextran: Dextran is used to increase the viscosity of the solution. | 34 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 8 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Control Treatment Arm | Total | Active Treatment Arm |
|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 16.9 | 62.3 years STANDARD_DEVIATION 15.89 | 61.8 years STANDARD_DEVIATION 15.3 |
| Autoimmune disease Graft Versus Host Disease | 1 Participants | 2 Participants | 1 Participants |
| Autoimmune disease Mucus Membrane Pemphigoid | 0 Participants | 1 Participants | 1 Participants |
| Autoimmune disease Rheumatoid Arthritis | 3 Participants | 4 Participants | 1 Participants |
| Autoimmune disease Steven Johnson Syndrome | 4 Participants | 7 Participants | 3 Participants |
| Autoimmune disease Vogt-Koyangi-Harada Syndrome | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 9 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 58 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Previous sterile keratolysis | 28 Participants | 56 Participants | 28 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 43 Participants | 20 Participants |
| Sex: Female, Male Female | 21 Participants | 41 Participants | 20 Participants |
| Sex: Female, Male Male | 13 Participants | 26 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 34 | 0 / 34 |
| other Total, other adverse events | 17 / 34 | 16 / 34 |
| serious Total, serious adverse events | 6 / 34 | 10 / 34 |
Outcome results
Primary
Time From Surgery to Device Loss or Replacement
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.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Treatment Arm | Time From Surgery to Device Loss or Replacement | 95 median weeks from surgery to removal |
| Control Treatment Arm | Time From Surgery to Device Loss or Replacement | 34 median weeks from surgery to removal |
Secondary
Median Time From Surgery to Occurrence of Vitritis (Sterile or Infectious)
The time (days) and number of incidences of vitritis will be recorded for the subject in which it occurred and the number of incidences will be compared between the study treatment groups.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Active Treatment Arm | Median Time From Surgery to Occurrence of Vitritis (Sterile or Infectious) | 188.6 median time (days) surgery to vitritis | Standard Deviation 218.4 |
| Control Treatment Arm | Median Time From Surgery to Occurrence of Vitritis (Sterile or Infectious) | 254.3 median time (days) surgery to vitritis | Standard Deviation 239.6 |
Secondary
Median Time From Surgery to Retroprosthetic Membrane Treatment in Days (Laser or Surgical Interventions)
If follow up surgery is needed to replace or treat the prosthetic the time and reason will be recorded and the number of incidences will be compared between the study treatment groups
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Active Treatment Arm | Median Time From Surgery to Retroprosthetic Membrane Treatment in Days (Laser or Surgical Interventions) | 300.3 median time (days) from surgery to RPM | Standard Deviation 194.7 |
| Control Treatment Arm | Median Time From Surgery to Retroprosthetic Membrane Treatment in Days (Laser or Surgical Interventions) | 253.37 median time (days) from surgery to RPM | Standard Deviation 158.11 |
Secondary
Number of Cumulative Delayed Epithelial Healing Events at Day 30
The number of incidences of delayed epithelial healing at day 30 will be recorded. If there is delayed epithelial healing at day 30 it will be determined if those incidences occurred more often in the control group versus the investigational group.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Treatment Arm | Number of Cumulative Delayed Epithelial Healing Events at Day 30 | 10 Participants |
| Control Treatment Arm | Number of Cumulative Delayed Epithelial Healing Events at Day 30 | 10 Participants |
Secondary
Number of Participants With Kpro Retention at 12 Months
The number of participants that retained kpro devices at the end of twelve months will be studied and differences in retention rate between investigational and control groups will be reported
Time frame: Twelve months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Treatment Arm | Number of Participants With Kpro Retention at 12 Months | 29 Participants |
| Control Treatment Arm | Number of Participants With Kpro Retention at 12 Months | 27 Participants |