Clinical trial NCT01482195: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Retinal Disease
Retinitis Pigmentosa
Keywords: Retinal Disease
subretinal gene therapy
MERTK
retinitis pigmentosa
Lead sponsor: King Khaled Eye Specialist Hospital
Sponsor class: OTHER_GOV
Collaborators: name: King Faisal Specialist Hospital & Research Center
First posted: 2011-11-30
Enrollment: 6
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Ocular Subretinal administration of rAAV2-VMD2-hMERTK .
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Systemic and Ocular Safety
timeFrame: 2 years
Secondary outcomes:
measure: Visual Acuity Measurement
timeFrame: 2 years and up to 5 years
measure: Full-field Stimulus Threshold Testing (FST).
timeFrame: 2 years
measure: Central Foveal Thickness (CFT) on Optical Coherence Tomography (OCT).
timeFrame: 2 years
measure: Central Macular Thickness (CMT) on Optical Coherence Tomography (OCT).
timeFrame: 2 years
Other outcomes:
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Khaled Eye Specialist Hospital
Study officials:
affiliation: King Faisal Specialist Hospital & Research Center
name: Fowzan S Alkuraya, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.