Epidermolysis Bullosa, Epidermolysis Bullosa Dystrophica
Conditions
Keywords
gene transfer
Brief summary
This trial will create a skin graft, which the investigators call LEAES, using the patient's own skin cells that have been genetically engineered in the lab to express a missing protein called type VII collagen. The corrected cells will be transplanted back to the patient.
Detailed description
The research project involves gene transfer into keratinocytes, which are the majority of the cells in the outer layer of skin. In this gene transfer trial we plan to biopsy some skin tissue, grow the cells in a skin cell culture (sterile dishes with special fluid that allows cells to grow and multiply) and then infect the cells with a virus that we have genetically engineered to insert the correct type VII collagen gene. The cells should then make type VII collagen. The process of inserting the correct type VII collagen gene into cells is called gene transfer. The virus used is called a retrovirus. The virus is made so that it only delivers the type VII collagen gene and it should not spread to other parts of the body. During the study we will check for growth of the virus. After cells have received gene transfer, we will grow the cells in culture into a sheet of cells that look like a plastic film. We plan to graft the sheet to wounds. Grafting means we will take cells from the culture and stitch them to the patient's skin.
Interventions
BIOLOGICALLZRSE-Col7A1 Engineered Autologous Epidermal Sheets
This trial will create a graft, which we call LEAES, of the patient's own skin that has been genetically engineered in our lab to express this missing protein.
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Stanford University
Abeona Therapeutics, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of recessive dystrophic epidermolysis bullosa (RDEB) 2. 13 years old or older and willing and able to give assent/consent 3. Confirmation of RDEB diagnosis by immunofluorescence (IF) and electron microscopy (EM) 4. NC1\[+\] and mAb LH24 antibody staining negative 5. RDEB type VII collagen mutations in subject and carrier parents confirmed 6. At least 100 to 200 cm2 areas of open erosions on the trunk and/or extremities suitable for skin grafting 7. Able to undergo adequate anesthesia to allow grafting procedures to take place.
Exclusion criteria
1. Medical instability limiting ability to travel to Stanford University Medical Center 2. The presence of medical illness expected to complicate participation and/or compromise the safety of this technique, such as active infection with HIV, hepatitis B or hepatitis C, as determined by hepatitis B surface antigen screening, detection of hepatitis C antibodies, or positive result of hepatitis C polymerase chain reaction (PCR) analysis. 3. Antibodies to type VII collagen associated antigens 4. Active infection in the area that will undergo grafting 5. Evidence of systemic infection 6. Current evidence or a history of squamous cell carcinoma in the area that will undergo grafting 7. Active drug or alcohol addiction 8. Hypersensitivity to vancomycin or amikacin 9. Receipt of chemical or biological study product for the specific treatment of RDEB in the past six months 10. Positive pregnancy test or breast-feeding 11. Clinically significant abnormalities (Grade 2 or higher on the National Cancer Institute \[NCI\] toxicity scale) on laboratory tests performed prior to grafting, except for the following specific exclusionary laboratory threshold results, subject to approval or exemption by the EB physician: * Albumin \< 2.5 g/dL * Leukocytes \> 20K/uL * Hemoglobin \< 7.5 g/dL. Low hemoglobin will be treated at the discretion of the investigators and the EB physician. * Additional exceptions may be made at the discretion of the investigators and the EB physician. 12. Clinically significant abnormalities (Grade 2 or higher on the NCI toxicity scale) identified through medical history and physical examination on Day 0, with the following exceptions: * Anorexia, can enroll up to Grade 4 (inclusive) * Constipation, can enroll up to Grade 2 (inclusive) * Dysphagia, can enroll up to Grade 4 (inclusive) * Keratitis, can enroll up to Grade 4 (inclusive) * Bone pain, can enroll up to Grade 2 (inclusive) * Additional exceptions may be made at the discretion of the investigators and the EB physician.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Wounds by Healing Category Per Investigator Visual Assessment | 3, 6, 12 and 24 months post grafting | The graft site was clinically evaluated by the investigator with a global score of: 1) 100% to 75% healed, 2) 74% to 50% healed, 3) 49% or less healed with 100% meaning completely healed. |
| Percentage Surface Area of Wound Healing | 3, 6 and 12 months post grafting | Percentage of wound area will be obtained using the Canfield system. Changes in dimensions between visits as well as changes in dimensions from baseline will be recorded. Dimensions of untreated wounded skin will be used for comparison |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 3 months, 6 months, 12 months, 24 months post-grafting | Skin biopsies were obtained to evaluate expression of type VII collagen, NC2 epitope, using immuno-electron microscopy and immuno-fluorescent light microscopy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Presence of Anchoring Fibrils (AF) | 3 months, 6 months, 12 months and 24 months post grafting | Skin biopsies were obtained to observe physical development of the anchoring fibrils using electron microscopy |
Countries
United States
Participant flow
Pre-assignment details
12 participants signed informed consent, 7 were allocated to the treatment arm.
Participants by arm
| Arm | Count |
|---|---|
| LEAES Treatment LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)
LZRSE-Col7A1 Engineered Autologous Epidermal Sheets: This trial will create a graft, which we call LEAES, of the patient's own skin that has been genetically engineered in our lab to express this missing protein. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | LEAES Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 2 / 7 |
Outcome results
Primary
Number of Wounds by Healing Category Per Investigator Visual Assessment
The graft site was clinically evaluated by the investigator with a global score of: 1) 100% to 75% healed, 2) 74% to 50% healed, 3) 49% or less healed with 100% meaning completely healed.
Time frame: 3, 6, 12 and 24 months post grafting
Population: The 7 participants who were determined to be eligible to receive LEAES cell sheets received 6 cell sheets to 6 wounds, each which were analyzed in this study as the primary endpoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|---|
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 3 months | Global Score of 100% to 75% | 35 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 3 months | Global Score of 74% to 50% | 5 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 3 months | Global Score of 49% or less | 2 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 6 months | Global Score of 49% or less | 11 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 12 months | Global Score of 100% to 75% | 19 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 12 months | Global Score of 74% to 50% | 11 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 6 months | Global Score of 100% to 75% | 28 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 6 months | Global Score of 74% to 50% | 3 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 12 months | Global Score of 49% or less | 12 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 24 months | Global Score of 100% to 75% | 26 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 24 months | Global Score of 74% to 50% | 5 wounds |
| LEAES Treatment | Number of Wounds by Healing Category Per Investigator Visual Assessment | 24 months | Global Score of 49% or less | 11 wounds |
Primary
Percentage Surface Area of Wound Healing
Percentage of wound area will be obtained using the Canfield system. Changes in dimensions between visits as well as changes in dimensions from baseline will be recorded. Dimensions of untreated wounded skin will be used for comparison
Time frame: 3, 6 and 12 months post grafting
Population: The Canfield Imaging System was implemented after the first 2 participants received LEAES. Tattoos were not used when placing tattoos for these first 2 participants. Therefore, measurements using the Canfield Imaging System was not possible.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound B | 98.7 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound C | 91.5 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound B | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound A | 70 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound D | 93.5 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound E | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound E | 89.45 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound E | 96 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound Z - induced | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound B | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound D | 96.67 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound A | 93.5 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound C | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound B | 89.8 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound C | 99 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound A | 92 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound D | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound D | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound F | 70 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound E | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound F | 99 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound E | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound Z - induced | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound A | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound D | 82 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound A | 96 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound F | 92 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound C | 100 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound B | 98 percentage of wound area |
| LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound C | 79 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound B | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound B | 99 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound A | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound E | 74.6 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound C | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound D | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound E | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound Z - induced | 35 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound A | 90.6 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound B | 81.6 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound C | 71 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound D | 85.5 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound Z - induced | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound A | 96 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound C | 32 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound D | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound E | 94.5 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound F | 97 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound A | 54 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound B | 81 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound C | 55 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound D | 73 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound E | 84 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound F | 48.8 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound A | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound B | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound C | 74 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound D | 82 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound E | 100 percentage of wound area |
| 6 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound F | 76 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound C | 78.56 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound C | 44 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound Z - induced | 90 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound E | 100 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound D | 29 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound E | 100 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound E | 75.7 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound E | 10 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound D | 97.5 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound D | 78.67 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound F | 31 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound C | 100 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound B | 26 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound A | 70 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound A | 85 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound C | 2 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound Z - induced | 100 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound B | 100 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound D | 87.5 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound F | 78.6 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound B | 100 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT07, Wound F | 95 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound C | 92 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT04, Wound A | 100 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound A | 12 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound B | 66.5 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT09, Wound E | 98.7 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT08, Wound B | 48 percentage of wound area |
| 12 Months Post LEAES Treatment | Percentage Surface Area of Wound Healing | GT05, Wound A | 78.6 percentage of wound area |
Secondary
Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production
Skin biopsies were obtained to evaluate expression of type VII collagen, NC2 epitope, using immuno-electron microscopy and immuno-fluorescent light microscopy.
Time frame: 3 months, 6 months, 12 months, 24 months post-grafting
Population: The 7 participants who were determined to be eligible to receive LEAES cell sheets received 6 cell sheets to 6 wounds, each which were analyzed in this study as the primary endpoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 3 months | Positive for NC2 | 7 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 3 months | Negative for NC2 | 0 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 3 months | Not done | 0 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 6 months | Positive for NC2 | 5 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 6 months | Negative for NC2 | 2 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 6 months | Not done | 0 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 12 months | Positive for NC2 | 2 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 12 months | Negative for NC2 | 4 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 12 months | Not done | 1 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 24 months | Positive for NC2 | 2 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 24 months | Negative for NC2 | 1 Participants |
| LEAES Treatment | Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production | 24 months | Not done | 4 Participants |
Other Pre-specified
Number of Participants With Presence of Anchoring Fibrils (AF)
Skin biopsies were obtained to observe physical development of the anchoring fibrils using electron microscopy
Time frame: 3 months, 6 months, 12 months and 24 months post grafting
Population: The 7 participants who were determined to be eligible to receive LEAES cell sheets received 6 cell sheets to 6 wounds, each which were analyzed in this study as the primary endpoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 12 months | Not done | 1 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 24 months | Positive for AFs | 1 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 24 months | Negative for AFs | 1 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 24 months | Not done | 5 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 3 months | Positive for AFs | 6 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 3 months | Negative for AFs | 1 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 3 months | Not done | 0 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 6 months | Positive for AFs | 5 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 6 months | Negative for AFs | 2 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 6 months | Not done | 0 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 12 months | Positive for AFs | 3 Participants |
| LEAES Treatment | Number of Participants With Presence of Anchoring Fibrils (AF) | 12 months | Negative for AFs | 3 Participants |