Safety and Tolerability of Subretinally Injected OPGx-BEST1 in Patients With Best Vitelliform Macular Dystrophy (BVMD) or Autosomal-Recessive Bestrophinopathy (ARB)

NCT07185256 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: OPGx-BEST1 DUO-1001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this clinical trial is to learn if drug OPGx-BEST1 works to treat BVMD and ARB Bestrophinopathy. It will also learn about the safety of drug OPGx-BEST1. The main questions it aims to answer are: Evaluate the safety and tolerability of drug OPGx-BEST1 in one eye (the treatment eye), for 5 years post-injection, in participants with BVMD or ARB. A second question it aims to answer is identification of the most appropriate dose strength of OPGx-BEST1 for clinical development. Evaluate the efficacy of single injection of OPGx-BEST1 in one eye for 5 years post-injection. What medical problems do participants have when taking drug OPGx-BEST1?

Conditions

ARB; BVMD; Autosomal-Dominant Bestrophinopathy; Best Vitelliform Macular Dystrophy

Keywords

Bestrophinopathy; BVMD; ARB; OPGx-BEST1; Best vitelliform macular dystrophy; Autosomal-Dominant Bestrophinopathy

Outcome Measures

Primary Outcomes (3)

• Number of dose-limiting toxicity (DLT) events at the dose tested

  Number of dose-limiting toxicity (DLT) events, defined as any ≥Grade 3 toxicity that occurs within 90 days after IMP administration based on the National Cancer Institute common toxicity criteria

  5 years

• Number and severity of procedure-related adverse events

  Number and severity of adverse events related to the administration of OPGx-BEST1 involving pars plana vitrectomy and subretinal injection under general anesthesia

  5 years

• Number and severity of adverse events related to OPGx-BEST1

  Number and severity of adverse events considered related to the study drug, OPGx-BEST1

  5 years

Secondary Outcomes (8)

• Changes from baseline in retinal morphology assessed by spectral-domain optical coherence tomography

  5 years

• Changes from baseline in retinal morphology assessed by 55 degree fundus autofluorescence (FAF)

  5 years

• Changes from baseline in retinal morphology assessed by ultra-wide angle autofluorescence (FAF)

  5 years

• Changes from baseline in neovascularization assessed by optical coherence tomography

  5 years

• Changes from baseline in retinal sensitivity

  5 years

Study Arms (1)

OPGx-BEST1

EXPERIMENTAL

OPGx-BEST1, 1.5E9 vg/eye injected one time subretinally

Genetic: OPGx-BEST1

Interventions

OPGx-BEST1 GENETIC

Experimental Genetic Therapy

OPGx-BEST1

Eligibility Criteria

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

You may qualify if:

• Individuals who meet all the following criteria will be eligible to participate in the study:
• Provide informed consent to study assessments.
• Able and willing to comply with all study assessments for the duration of the study.
• ≥18 years old.
• ETDRS BCVA measured with standard testing distances:
• For the sentinel participant in each cohort, ≤20 letters (Snellen equivalent of 20/200 \[1.30 logMAR\] or worse)
• For subsequent participants in the same cohort, 65 to 20 letters inclusive (Snellen equivalent of 20/50 \[0.40 logMAR\] to 20/200 \[1.30 logMAR\]).
• Genetic confirmation on chromosome 11q12-q13.1 of BVMD or ARB with a BEST1 genetic test or IRD panel test including a BEST1 variant test, by a Clinical Laboratory Improvement Amendments (CLIA) or European certified laboratory. If available test result is more than 15 years old, confirmation testing will be performed at Visit 1, with results needed by Visit 3.
• Confirmation of one disease-causing (pathogenic or likely pathogenic, autosomal-dominant) variant in the BEST1 gene for BVMD, as listed in the IB, or two variants for ARB per American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant interpretation.
• BVMD: Clinical phenotype and diagnosis consistent with advanced BVMD with active subretinal fluid or vitelliform material.
• ARB: Clinical phenotype and diagnosis consistent with ARB.

You may not qualify if:

• Individuals who meet any of the following criteria will not be eligible to participate in the study.
• Women of childbearing potential (WOCBP) who are pregnant, lactating, and/or unwilling to use effective contraception from Screening through 1 year after IMP administration. See Section 13.3 (Appendix 3) for contraception guidelines.
• Men who are unwilling to use adequate contraception from Screening through 180 days after IMP administration. See Section 13.3 (Appendix 3) for contraception guidelines.
• Have a pre-existing eye condition or complicating systemic disease that could preclude the planned surgery (e.g., individuals who are immunocompromised, on continuous systemic immunosuppressive treatment or anticipate a need to initiate it for non-study reasons, or unable to take the concomitant immuno-suppressive regimen necessary for IMP administration).
• Have a history of disease that may preclude the individual from study participation (e.g., other bestrophinopathy, such as AOFVD or ADVIRC) or that may interfere with or preclude outcome measure testing as described in the protocol.
• Have previously received gene therapy of any kind.
• Presence of active choroidal neovascularization (CNV) that, in the opinion of the Investigator, affects vision or may require treatment.
• Presence of subretinal fibrosis that may significantly limit improvement in visual acuity.
• Have an epiretinal membrane that may require surgical intervention.
• Had intraocular surgery within 90 days prior to planned IMP administration or have active inflammation at Screening resulting from prior ocular surgery.
• Have used any investigational drug or device within 90 days prior to planned IMP administration or plan to participate in another drug or device study during the same period as the current study.
• Have received a vaccination within 6 weeks prior to planned IMP administration or plan to be vaccinated within 6 months after IMP administration.
• Have received anticoagulant therapy within 2 weeks prior to planned IMP administration.
• Have active macular neovascularization as determined by OCT-A.
• Are incapable of performing visual function testing for reasons other than poor vision.

Sponsors & Collaborators

• Opus Genetics, Inc: lead

Study Sites (4)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Vitreo Retinal Associates

Gainesville, Florida, 34481, United States

NOT YET RECRUITING

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

RECRUITING

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

RECRUITING

Related Links

• Opus website with description of programs

MeSH Terms

Conditions

Vitelliform Macular Dystrophy; Bestrophinopathy

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Study Director

CONTACT

984-884-6030; ct.gov_inquiries@opusgtx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: September 22, 2025
• Study Start: September 25, 2025
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)