ARBPhase 1/2BIRD-1NCT07185256
Safety and Tolerability of Subretinally Injected OPGx-BEST1 in Patients With Best Vitelliform Macular Dystrophy (BVMD) or Autosomal-Recessive Bestrophinopathy (ARB)
A Phase 1/2 study testing OPGx-BEST1 in people with ARB and BVMD, run by Opus Genetics, Inc at 5 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ARB, BVMD, Autosomal-Dominant Bestrophinopathy
- What is being tested?
- OPGx-BEST1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 5 sitesUnited States
- Study dates
- 25 Sep 2025to Aug 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
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- 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.
- Have undergone tube surgery for glaucoma at any time or have glaucoma that has been unstable within the past 4 years. Note: Prior incisional surgery (e.g., trabeculectomy and iridotomy) is not exclusionary.
- 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.
- Have any contraindication to the concomitant steroid regiment proscribed in the protocol.
- Have any other condition (ocular, medical, or psychological) that would not allow the individual to complete follow-up examinations during the study and/or, in the opinion of the Investigator, makes it hazardous or unsuitable for the individual to participate in the study.
- Have a known history of hypersensitivity to constituents or excipients in the pharmaceutical formulation of the IMP.
- Have a known infection of human immunodeficiency virus (HIV), hepatitis B or C virus, or herpes simplex virus.
- Are an employee of the Sponsor or a relative of the Investigator or investigative site staff.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
Cincinnati Eye Institute
Cincinnati, Ohio, 45242
Cincinnati Eye Institute Clinical Research Department, 513-569-3688, cvp-research@cvphealth.com
Robert Sisk, MD
- Recruiting
Retina Foundation of the Southwest
Dallas, Texas, 75231
Kaylie Jones, MS, 214-363-3911, kwebb@retinafoundation.org
Mark Pennesi, MD
- Not yet recruiting
Vitreo Retinal Associates
Gainsville, Florida, 34481
Hailey Ahrens, 352-300-4212, hailey@vra-pa.com
Christine Kay, MD
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027
Hillary Schwartz-Gale, 323-361-1004, hschwartz@chla.usc.edu
Aaron Nagiel, MD
- Recruiting
Harkness Eye Institute, CColumbia University Irving Medical Center
New York, New York, 10032
Maribel Rodriguez, 212-305-1407, mr3208@cumc.columbia.edu
Jason Horowitz, MD
About this study
Official title: A Phase 1b/2a, Open-Label, Dose-Exploration Basket Study to Investigate the Safety and Tolerability of Subretinally Injected OPGx-BEST1 Administered in Patients With Either Autosomal-Dominant BEST1 Disease (Best Vitelliform Macular Dystrophy [BVMD]) or Autosomal-Recessive Bestrophinopathy (ARB)
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?
Read the detailed description
This is a Phase 1b/2a, open-label, dose-exploring, safety and tolerability basket study of a single subretinal injection of OPGx-BEST1 in one eye of adult participants with ARB or BVMD due to BEST1 mutations.
OPGx-BEST1 has been bioengineered to include a transgene expression cassette with a codon-optimized, full-length hBEST1 gene under the control of an RPE-specific promoter. The vector genome contains inverted terminal repeats flanking an expression cassette containing the VMD2 promoter, full-length BEST1 ORF followed by SV 40 and bGH polyadenylation signal sequences, and lastly includes a kanamycin resistance gene. The Kozak sequence (upstream of the start codon) enhances the translation from the correct initiation codon. Selection of the VMD2 promoter was done to restrict the expression to the target cell type and drive expression levels comparable to those in photoreceptors. This intervention is a one-time injection.
Two vector doses are proposed for evaluation: 1.5E9 vg/eye (Cohort 1) and 4.5E9 vg/eye (Cohort 2). A minimum of 5 evaluable participants will be treated at each dose level, starting with a sentinel participant in Cohort 1. An Independent Data Monitoring Committee (IDMC) will evaluate safety 30 days after treatment of the sentinel participant before the remaining 4 participants in Cohort 1 are eligible for treatment. After the last participant has completed the Month 3 visit, the IDMC will review all Cohort 1 data and determine whether to initiate enrollment in Cohort 2 or adjust the dose escalation scheme.
Each participant will have a Screening visit and two-part Baseline visit. On Day 1 (Visit 4), participants will undergo vitrectomy with subretinal injection of OPGx-BEST1 at the preassigned dose. Participants will return for follow-up on Day 2, Day 7, Day 14, Day 30, and Day 45 following IMP administration (Visits 5-9). Participants will also return 3 and 6 months following IMP administration (Visits 10-11) and 1, 1.5, 2, 3, 4, and 5 years following IMP administration (Visits 12-17).
Post-IMP administration, safety and efficacy outcomes will be evaluated for 5 years.
In addition to the primary objectives of establishing IMP safety and tolerability and identifying the most appropriate dose strength, the study will evaluate the preliminary efficacy of OPGx-BEST1 and characterize the immunogenic effects of administration. A central reading center will provide standardized evaluation of select imaging data. Analysis of results will include treatment-eye comparisons of visual function post-administration of OPGx-BEST1 to baseline visual function.
- Being tested
- OPGx-BEST1
- Keywords
- Bestrophinopathy, BVMD, ARB, OPGx-BEST1, Best vitelliform macular dystrophy, Autosomal-Dominant Bestrophinopathy
- Medical subject headings
- Vitelliform Macular Dystrophy, Bestrophinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPGx-BEST1Genetic
Experimental Genetic Therapy
| Study group | Role | What they receive |
|---|---|---|
| OPGx-BEST1 | Experimental | OPGx-BEST1, 1.5E9 vg/eye injected one time subretinally Receives: Genetic: OPGx-BEST1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 5 years
Secondary outcomes (8)
Changes from baseline in retinal morphology assessed by spectral-domain optical coherence tomography
Changes from baseline in retinal morphology assessed by spectral-domain optical coherence tomography
Measured: 5 years
Changes from baseline in retinal morphology assessed by 55 degree fundus autofluorescence (FAF)
Changes from baseline in retinal morphology assessed by 55 degree fundus autofluorescence (FAF)
Measured: 5 years
Changes from baseline in retinal morphology assessed by ultra-wide angle autofluorescence (FAF)
Changes from baseline in retinal morphology assessed by ultra-wide angle autofluorescence (FAF)
Measured: 5 years
Changes from baseline in neovascularization assessed by optical coherence tomography
Changes from baseline in neovascularization assessed by optical coherence tomography angiography
Measured: 5 years
Changes from baseline in retinal sensitivity
Changes from baseline in retinal sensitivity assessed by microperimetry
Measured: 5 years
Changes from baseline in best corrected visual acuity
Changes from baseline in best corrected visual acuity letter score as measured by Early Treatment Diabetic Retinopathy Stuidy (ETDRS) charts
Measured: 5 years
Changes from baseline in low luminance visual acuity
Changes from baseline in low luminance visual acuity assessed by ETDRS charts
Measured: 5 years
Changes from baseline in participant-reported outcomes
Changes from baseline in participant-reported outcomes assessed by the Michigan Retinal Degeneration Questionnaire
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2025
- Study start25 Sep 2025
- Primary completionAug 2030 (estimated)
- Study completionAug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ARBStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Opus Genetics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07185256
- Sponsor's protocol ID
- OPGx-BEST1 DUO-1001
- Acronym
- BIRD-1
- Status last verified
- Sep 2026
- First submitted
- 17 Jul 2025
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2a, Open-Label, Dose-Exploration Basket Study to Investigate the Safety and Tolerability of Subretinally Injected OPGx-BEST1 Administered in Patients With Either Autosomal-Dominant BEST1 Disease (Best Vitelliform Macular Dystrophy [BVMD]) or Autosomal-Recessive Bestrophinopathy (ARB)
- ClinicalTrials.gov ID
- NCT07185256
- Acronym / sponsor ID
- BIRD-1 / OPGx-BEST1 DUO-1001
- Keywords
- Bestrophinopathy, BVMD, ARB, OPGx-BEST1, Best vitelliform macular dystrophy, Autosomal-Dominant Bestrophinopathy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Opus Genetics, IncIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2025 (actual)
- Primary completion
- Aug 2030 (estimated)
- Study completion
- Aug 2030 (estimated)
- First posted
- 22 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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?
Detailed description
This is a Phase 1b/2a, open-label, dose-exploring, safety and tolerability basket study of a single subretinal injection of OPGx-BEST1 in one eye of adult participants with ARB or BVMD due to BEST1 mutations.
OPGx-BEST1 has been bioengineered to include a transgene expression cassette with a codon-optimized, full-length hBEST1 gene under the control of an RPE-specific promoter. The vector genome contains inverted terminal repeats flanking an expression cassette containing the VMD2 promoter, full-length BEST1 ORF followed by SV 40 and bGH polyadenylation signal sequences, and lastly includes a kanamycin resistance gene. The Kozak sequence (upstream of the start codon) enhances the translation from the correct initiation codon. Selection of the VMD2 promoter was done to restrict the expression to the target cell type and drive expression levels comparable to those in photoreceptors. This intervention is a one-time injection.
Two vector doses are proposed for evaluation: 1.5E9 vg/eye (Cohort 1) and 4.5E9 vg/eye (Cohort 2). A minimum of 5 evaluable participants will be treated at each dose level, starting with a sentinel participant in Cohort 1. An Independent Data Monitoring Committee (IDMC) will evaluate safety 30 days after treatment of the sentinel participant before the remaining 4 participants in Cohort 1 are eligible for treatment. After the last participant has completed the Month 3 visit, the IDMC will review all Cohort 1 data and determine whether to initiate enrollment in Cohort 2 or adjust the dose escalation scheme.
Each participant will have a Screening visit and two-part Baseline visit. On Day 1 (Visit 4), participants will undergo vitrectomy with subretinal injection of OPGx-BEST1 at the preassigned dose. Participants will return for follow-up on Day 2, Day 7, Day 14, Day 30, and Day 45 following IMP administration (Visits 5-9). Participants will also return 3 and 6 months following IMP administration (Visits 10-11) and 1, 1.5, 2, 3, 4, and 5 years following IMP administration (Visits 12-17).
Post-IMP administration, safety and efficacy outcomes will be evaluated for 5 years.
In addition to the primary objectives of establishing IMP safety and tolerability and identifying the most appropriate dose strength, the study will evaluate the preliminary efficacy of OPGx-BEST1 and characterize the immunogenic effects of administration. A central reading center will provide standardized evaluation of select imaging data. Analysis of results will include treatment-eye comparisons of visual function post-administration of OPGx-BEST1 to baseline visual function.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OPGx-BEST1 | Experimental | Genetic: OPGx-BEST1OPGx-BEST1, 1.5E9 vg/eye injected one time subretinally |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OPGx-BEST1Experimental Genetic Therapy | Genetic | OPGx-BEST1 |
Primary outcome
Number of dose-limiting toxicity (DLT) events at the dose tested
Time frame: 5 years
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
Number and severity of procedure-related adverse events
Time frame: 5 years
Number and severity of adverse events related to the administration of OPGx-BEST1 involving pars plana vitrectomy and subretinal injection under general anesthesia
Number and severity of adverse events related to OPGx-BEST1
Time frame: 5 years
Number and severity of adverse events considered related to the study drug, OPGx-BEST1
8 secondary outcomes
Changes from baseline in retinal morphology assessed by spectral-domain optical coherence tomography
Time frame: 5 years
Changes from baseline in retinal morphology assessed by 55 degree fundus autofluorescence (FAF)
Time frame: 5 years
Changes from baseline in retinal morphology assessed by ultra-wide angle autofluorescence (FAF)
Time frame: 5 years
Changes from baseline in neovascularization assessed by optical coherence tomography
Time frame: 5 years
Changes from baseline in retinal sensitivity
Time frame: 5 years
Changes from baseline in best corrected visual acuity
Time frame: 5 years
Changes from baseline in low luminance visual acuity
Time frame: 5 years
Changes from baseline in participant-reported outcomes
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Opus website with description of programsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing OPGx-BEST1 in people with ARB and BVMD, run by Opus Genetics, Inc at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Director (984-884-6030, ct.gov_inquiries@opusgtx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of dose-limiting toxicity (DLT) events at the dose tested (time frame: 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026; AzTrials last refreshed its copy on 8 Nov 2026.