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| Name | Class |
|---|---|
| King Faisal Specialist Hospital & Research Center | OTHER |
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This study was to assess the safety of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK in subjects with MERTK-associated retinitis pigmentosa (RP).
In this phase I open-label, dose-escalation trial, one eye of each patient (the worse-seeing eye in five subjects) will receive a submacular injection of the subretinal rAAV2-VMD2-hMERTK. Patients will be followed daily for 10 days and then at 30, 60, 90, 180, 270, 365, 540, and 730 days post-injection. Data will be collected on (1) full ophthalmologic examination including best-corrected VA, intraocular pressure, color fundus photographs, macular spectral-domain optical coherence tomography, and full-field stimulus threshold test (FST) in both the study and fellow eyes; (2) systemic safety data including CBC, liver, and kidney function tests, coagulation profiles, urine analysis, AAV antibody titers, peripheral blood PCR and ASR measurement; and (3) listing of ophthalmological or systemic adverse effects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subretinal Injection of rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus | Experimental | Single arm of 6 patients undergoing subretinal injection of Gene Therapy using rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus. Each patient received the injection in one eye. |
|
| fellow eye without intervention | No Intervention | fellow eye without intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Subretinal administration of rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus | Biological | The study is an open-label, dose-escalation, phase I clinical trial of subretinal administration of rAAV2-VMD2-hMERTK in patients with retinitis pigmentosa due to MERTK mutation. |
| Measure | Description | Time Frame |
|---|---|---|
| Systemic and Ocular Safety | Detailed history & physical exam were obtained at baseline visit and each post-injection protocol visit searching for systemic adverse events. Included were electrocardiogram, chest X-ray, complete blood count & differential, prothrombin time & INR, partial thromboplastin time, serum electrolytes, full serum chemistries including liver and renal function, urinalysis; serum antibody titers to AAV2 capsid components and antigen-specific reactivity (ASR) assays; blood analysis by DNA PCR to detect vector spread. Ophthalmic safety monitored changes from baseline included 1) corneal abnormalities, afferent pupillary defect, intraocular inflammation, cataract & intraocular pressure changes; 2) retinal changes based on fundus photos; 3) Macular SD-OCT changes in Central macular (CMT) and central foveal thickness (CFT) measurements when patient fixation allowed it, and 4) full field stimulus threshold (FST) to detect any retinal toxicity . | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Visual Acuity Measurement | Although candidates may have very severe loss of function, an attempt was made to measure a best-corrected visual acuity using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, and measurements were recorded as the number of letters read on each line of the chart (Diabetic Retinopathy Study Research Group 1985). If a patient was unable to read at least three letters of the first line correctly, the chart distance was progressively halved from the standard 4 m until either the first line was correctly read or the shortest distance of 0.5 m was reached. Patients who were unable to read any letters on the chart were tested for light perception and if they perceived light they were assigned the acuity score equivalent of <20/6400. Measurements were performed at baseline and each protocol follow up visit. Improvement in patients who could read was defined as a gain in 5 letters, and in those with those LP vision only to start seeing hand motion. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fowzan S Alkuraya, MD | King Faisal Specialist Hospital & Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| King Khaled Eye Specialist Hospital | Riyadh | 11462 | Saudi Arabia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40547876 | Derived | Wang CY, Chen L, Lin TY, Huang SP. Systematic Identification of Candidate Genes for Inherited Retinal Disease Gene Therapy Integrating Worldwide IRD Cohort and Single-Cell Analysis. J Ophthalmol. 2025 Jun 12;2025:7014745. doi: 10.1155/joph/7014745. eCollection 2025. | |
| 26427420 | Derived | Parinot C, Nandrot EF. A Comprehensive Review of Mutations in the MERTK Proto-Oncogene. Adv Exp Med Biol. 2016;854:259-65. doi: 10.1007/978-3-319-17121-0_35. |
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Six eyes of 6 patients were enrolled in this phase of the study. All patients had the typical clinical signs and symptoms of retinitis pigmentosa and tested positive for MERTK mutation. All patients were recruited from the outpatient clinics at King Khaled Eye specialist Hospital (KKESH) starting September 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | Recombinant Adeno-Associated Virus | Recombinant Adeno-Associated Virus: Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Recombinant Adeno-Associated Virus | Recombinant Adeno-Associated Virus: Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Systemic and Ocular Safety | Detailed history & physical exam were obtained at baseline visit and each post-injection protocol visit searching for systemic adverse events. Included were electrocardiogram, chest X-ray, complete blood count & differential, prothrombin time & INR, partial thromboplastin time, serum electrolytes, full serum chemistries including liver and renal function, urinalysis; serum antibody titers to AAV2 capsid components and antigen-specific reactivity (ASR) assays; blood analysis by DNA PCR to detect vector spread. Ophthalmic safety monitored changes from baseline included 1) corneal abnormalities, afferent pupillary defect, intraocular inflammation, cataract & intraocular pressure changes; 2) retinal changes based on fundus photos; 3) Macular SD-OCT changes in Central macular (CMT) and central foveal thickness (CFT) measurements when patient fixation allowed it, and 4) full field stimulus threshold (FST) to detect any retinal toxicity . | Posted | Count of Participants | Participants | 2 years |
|
through study completion, an average of 2 years
The adverse events were collected :
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Recombinant Adeno-Associated Virus | Recombinant Adeno-Associated Virus: Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Filamentary keratitis | Eye disorders | Systematic Assessment | resolved with postoperative lubrication therapy |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Fowzan Al Kuraya | King Faisal Specialist Hospital and Research Center | +966 11 442 7875 | falkuraya@kfshrc.edu.sa |
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| ID | Term |
|---|---|
| D012164 | Retinal Diseases |
| D012174 | Retinitis Pigmentosa |
| ID | Term |
|---|---|
| D005128 | Eye Diseases |
| D015785 | Eye Diseases, Hereditary |
| D058499 | Retinal Dystrophies |
| D012162 | Retinal Degeneration |
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Ocular Subretinal administration of rAAV2-VMD2-hMERTK .
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| 2 years and up to 5 years |
| Full-field Stimulus Threshold Testing (FST). | Full-field stimulus threshold testing (FST) measures sensitivity of the entire visual field by estimating the lowest luminance of a flash that elicits a visual sensation. The FST measurements were performed at baseline and throughout the protocol visits over two years in the study and fellow eyes, and changes in FST results were analyzed. | 2 years |
| Central Foveal Thickness (CFT) on Optical Coherence Tomography (OCT). | Central foveal thickness (CFT) measurements were performed at baseline and throughout the protocol visits over two years in the study and fellow eyes (whenever possible), and changes in CFT values were analyzed. | 2 years |
| Central Macular Thickness (CMT) on Optical Coherence Tomography (OCT). | Central macular thickness (CMT) measurements were performed at baseline and throughout the protocol visits over two years in the study and fellow eyes (whenever possible), and changes in CMT values were analyzed. | 2 years |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Eyes with RP which received a single dose of subretinal recombinant Adeno-Associated Virus injection. |
| OG001 | Fellow Eyes | Eyes with RP which did not receive subretinal recombinant Adeno-Associated Virus injection. |
|
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| Secondary | Visual Acuity Measurement | Although candidates may have very severe loss of function, an attempt was made to measure a best-corrected visual acuity using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, and measurements were recorded as the number of letters read on each line of the chart (Diabetic Retinopathy Study Research Group 1985). If a patient was unable to read at least three letters of the first line correctly, the chart distance was progressively halved from the standard 4 m until either the first line was correctly read or the shortest distance of 0.5 m was reached. Patients who were unable to read any letters on the chart were tested for light perception and if they perceived light they were assigned the acuity score equivalent of <20/6400. Measurements were performed at baseline and each protocol follow up visit. Improvement in patients who could read was defined as a gain in 5 letters, and in those with those LP vision only to start seeing hand motion. | Posted | Count of Participants | Participants | 2 years and up to 5 years |
|
|
|
| Secondary | Full-field Stimulus Threshold Testing (FST). | Full-field stimulus threshold testing (FST) measures sensitivity of the entire visual field by estimating the lowest luminance of a flash that elicits a visual sensation. The FST measurements were performed at baseline and throughout the protocol visits over two years in the study and fellow eyes, and changes in FST results were analyzed. | Six Patients with the clinical diagnosis of RP with a proven MERTK mutation were included. Patients had to be older than 14 years of age and had the viral vector injected into their worse seeing one eye (except case #4). | Posted | Mean | 95% Confidence Interval | dB | 2 years |
|
|
|
| Secondary | Central Foveal Thickness (CFT) on Optical Coherence Tomography (OCT). | Central foveal thickness (CFT) measurements were performed at baseline and throughout the protocol visits over two years in the study and fellow eyes (whenever possible), and changes in CFT values were analyzed. | Posted | Mean | 95% Confidence Interval | microns. | 2 years |
|
|
|
| Secondary | Central Macular Thickness (CMT) on Optical Coherence Tomography (OCT). | Central macular thickness (CMT) measurements were performed at baseline and throughout the protocol visits over two years in the study and fellow eyes (whenever possible), and changes in CMT values were analyzed. | Posted | Mean | 95% Confidence Interval | microns. | 2 years |
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| 0 |
| 6 |
| 0 |
| 6 |
| 3 |
| 6 |
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| delayed resolution of subretinal fluid postoperatively, cataract, oscillopsia | Eye disorders | Systematic Assessment | The fluid resolved spontaneously within 6 weeks after surgery with return of vision to baseline. The same patient developed posterior subcapsular cataract and persistent oscillopsia in the operated eye and the cause remains unknown. |
|
| systemic | Blood and lymphatic system disorders | Systematic Assessment | One patient developed a rise in AAV antibodies but with a negative PCR. Serum AAV antibody and antigen specific reactivity measurements for the remaining patients are negative |
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| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| Stable VA at 2 years |
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| Improvement of VA after 2years |
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| FST at 10 days |
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| FST at 30 days |
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| FST at 90 days |
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| FST at 180 days |
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| FST at 365 days |
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| FST at 1.5 year |
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| FST at 2 years |
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