Back to resultsTrial of Subretinal Injection of (rAAV2-VMD2-hMERTK)
Primary Purpose
Retinal Disease, Retinitis Pigmentosa
Status
Completed
Phase
Phase 1
Locations
Saudi Arabia
Study Type
Interventional
Intervention
Subretinal administration of rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus
Sponsored by
About this trial
This is an interventional treatment trial for Retinal Disease focused on measuring Retinal Disease, subretinal gene therapy, MERTK, retinitis pigmentosa
Eligibility Criteria
Inclusion Criteria:
- MERTK-associated retinal disease;
- VA: 20/100 or less in worse eye
- Ability to perform tests of visual and retinal function;
- Good general health based on a complete physical examination and hematology and chemistry studies performed at a pre-treatment evaluation;
- Ability to comply with research procedures;
Exclusion Criteria:
- Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or surgical complications (for example, glaucoma, corneal or lenticular opacities);
- Complicating systemic diseases (such as medical conditions causing immunosuppression) that would preclude the gene transfer, ocular surgery or known sensitivity or allergy to medications planned for use in the peri-operative period;
- Use of anti-platelet agents that may alter coagulation within 7 days prior to study agent administration;
- Use of immunosuppressive medications;
- Pregnancy or breastfeeding;
- Individuals (males and females) of childbearing potential who are unwilling to use effective contraception for 1 year following agent administration and barrier contraception for 3 months following agent administration;
- Any other condition that would prevent a subject from completing follow-up examinations during the course of the study and that, in the opinion of the investigator, makes the subject unsuitable for the study.
- Current, or recent (within the past 30 days, or 10 half lives of the drug) participation, in any other research protocol involving investigational agents or therapies.
- Recent (within past 6 months) receipt of an investigational biologic therapeutic agent.Subjects will not be excluded based on their gender, race or ethnicity.
Sites / Locations
- King Khaled Eye Specialist Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Subretinal Injection of rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus
fellow eye without intervention
Arm Description
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
Outcomes
Primary Outcome Measures
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 .
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
NCT ID
NCT01482195
First Posted
September 28, 2011
Last Updated
January 25, 2022
Sponsor
King Khaled Eye Specialist Hospital
Collaborators
King Faisal Specialist Hospital & Research Center
1. Study Identification
Unique Protocol Identification Number
NCT01482195
Brief Title
Trial of Subretinal Injection of (rAAV2-VMD2-hMERTK)
Official Title
Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-VMD2-hMERTK) Gene Vector to Patients With Retinal Disease Due to MERTK Mutations
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
August 2011 (Actual)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
King Khaled Eye Specialist Hospital
Collaborators
King Faisal Specialist Hospital & Research Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinal Disease, Retinitis Pigmentosa
Keywords
Retinal Disease, subretinal gene therapy, MERTK, retinitis pigmentosa
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Ocular Subretinal administration of rAAV2-VMD2-hMERTK .
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Subretinal Injection of rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus
Arm Type
Experimental
Arm Description
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.
Arm Title
fellow eye without intervention
Arm Type
No Intervention
Arm Description
fellow eye without intervention
Intervention Type
Biological
Intervention Name(s)
Subretinal administration of rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus
Intervention Description
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.
Primary Outcome Measure Information:
Title
Systemic and Ocular Safety
Description
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 .
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Visual Acuity Measurement
Description
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.
Time Frame
2 years and up to 5 years
Title
Full-field Stimulus Threshold Testing (FST).
Description
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.
Time Frame
2 years
Title
Central Foveal Thickness (CFT) on Optical Coherence Tomography (OCT).
Description
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.
Time Frame
2 years
Title
Central Macular Thickness (CMT) on Optical Coherence Tomography (OCT).
Description
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.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
MERTK-associated retinal disease;
VA: 20/100 or less in worse eye
Ability to perform tests of visual and retinal function;
Good general health based on a complete physical examination and hematology and chemistry studies performed at a pre-treatment evaluation;
Ability to comply with research procedures;
Exclusion Criteria:
Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or surgical complications (for example, glaucoma, corneal or lenticular opacities);
Complicating systemic diseases (such as medical conditions causing immunosuppression) that would preclude the gene transfer, ocular surgery or known sensitivity or allergy to medications planned for use in the peri-operative period;
Use of anti-platelet agents that may alter coagulation within 7 days prior to study agent administration;
Use of immunosuppressive medications;
Pregnancy or breastfeeding;
Individuals (males and females) of childbearing potential who are unwilling to use effective contraception for 1 year following agent administration and barrier contraception for 3 months following agent administration;
Any other condition that would prevent a subject from completing follow-up examinations during the course of the study and that, in the opinion of the investigator, makes the subject unsuitable for the study.
Current, or recent (within the past 30 days, or 10 half lives of the drug) participation, in any other research protocol involving investigational agents or therapies.
Recent (within past 6 months) receipt of an investigational biologic therapeutic agent.Subjects will not be excluded based on their gender, race or ethnicity.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fowzan S Alkuraya, MD
Organizational Affiliation
King Faisal Specialist Hospital & Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
King Khaled Eye Specialist Hospital
City
Riyadh
ZIP/Postal Code
11462
Country
Saudi Arabia
12. IPD Sharing Statement
Citations:
PubMed Identifier
26427420
Citation
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.
Results Reference
derived
Learn more about this trial
Trial of Subretinal Injection of (rAAV2-VMD2-hMERTK)
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