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

NCT01482195 | Completed Phase 1 Results DMC

• 1 other identifier: 0916-P
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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).

Conditions

Retinal Disease; Retinitis Pigmentosa

Keywords

Retinal Disease; subretinal gene therapy; MERTK; retinitis pigmentosa

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Visual Acuity Measurement

  2 years and up to 5 years

• Full-field Stimulus Threshold Testing (FST).

  2 years

• Central Foveal Thickness (CFT) on Optical Coherence Tomography (OCT).

  2 years

• Central Macular Thickness (CMT) on Optical Coherence Tomography (OCT).

  2 years

Study Arms (2)

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.

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

fellow eye without intervention

NO INTERVENTION

fellow eye without intervention

Interventions

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.

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

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• King Khaled Eye Specialist Hospital: lead
• King Faisal Specialist Hospital & Research Center: collaborator

Study Sites (1)

King Khaled Eye Specialist Hospital

Riyadh, 11462, Saudi Arabia

Location

Related Publications (2)

• 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.

  PMID: 40547876 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.

  PMID: 26427420 DERIVED

MeSH Terms

Conditions

Retinal Diseases; Retinitis Pigmentosa

Condition Hierarchy (Ancestors)

Eye Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Degeneration; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Dr. Fowzan Al Kuraya
• Organization: King Faisal Specialist Hospital and Research Center

falkuraya@kfshrc.edu.sa

+966 11 442 7875

Study Officials

• Fowzan S Alkuraya, MD

  King Faisal Specialist Hospital & Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Ocular Subretinal administration of rAAV2-VMD2-hMERTK .

Study Record Dates

• First Submitted: September 28, 2011
• First Posted: November 30, 2011
• Study Start: August 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2019
• Last Updated: January 26, 2022
• Results First Posted: July 15, 2021

Record last verified: 2022-01

Locations

SA (1)