Trial of Subretinal Injection of (rAAV2-VMD2-hMERTK)

NCT ID: NCT01482195

Last Updated: 2022-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2019-08-31

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.

Conditions

Retinal Disease; Retinitis Pigmentosa

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subretinal Injection of rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus

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.

Group Type: EXPERIMENTAL

Subretinal administration of rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus

Intervention Type: 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.

fellow eye without intervention

fellow eye without intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Subretinal administration of rAAV2-VMD2-hMERTKRecombinant Adeno-Associated Virus

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.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King Faisal Specialist Hospital & Research Center

OTHER

Sponsor Role: collaborator

King Khaled Eye Specialist Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fowzan S Alkuraya, MD

Role: PRINCIPAL_INVESTIGATOR

King Faisal Specialist Hospital & Research Center

Locations

King Khaled Eye Specialist Hospital

Riyadh, , Saudi Arabia

Countries

Saudi Arabia

References

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.

Reference Type: DERIVED

PMID: 40547876 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26427420 (View on PubMed)

Other Identifiers

0916-P

Identifier Type: -

Identifier Source: org_study_id