LCA5Phase 1/2NCT05616793
Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm With Untreated Patients
A Phase 1/2 study testing AAV8.hLCA5 in people with LCA5, run by Opus Genetics, Inc at 2 sites in United States.
Trial summary
The goals of this clinical trial are assess the natural course of LCA5-IRD over 6 months and to evaluate the safety and preliminary efficacy of subretinal gene therapy with OPGx-001 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- LCA5
- What is being tested?
- AAV8.hLCA5
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Jun 2023to 15 Jun 2028
- 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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Are willing and able to provide written informed consent (ICF) and, where appropriate, willing to sign an assent prior to any study procedures.
- Are willing to adhere to the clinical protocol and able to perform testing procedures.
- In part A participants must be 13 years of age or older at consent, for Part B, participants must be 4 years of age or older at consent with the ability to conduct the MLoMT.
- Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (historic testing up to 15 years from date of consent can be considered).
- Visual acuity: BCVA < 20/80 on the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart (modified for low vision participants) in the eye to be treated
- Show evidence of detectable photoreceptors by Spectral Domain Optical Coherence Tomography (SD-OCT)
- Participant is a good candidate for surgery per investigator judgement
- Participant agrees to follow direction of investigator regarding restrictions post-surgery (Part A only).
Who cannot join
- Women who are pregnant or individuals (women of childbearing potential and men) unwilling to use effective contraception for the duration of the study, including barrier methods for the first year after investigational product (IP) administration (Part A only).
- Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery. This includes individuals who are immunocompromised.
- History of intraocular surgery for either eye within 6 months prior to planned IP administration (Part A only).
- Have previously received gene therapy.
- Have used any investigational drug or device within 90 days or 5 estimated half-lives of treatment, whichever is longer or plan to participate in another study of drug or device during the study period.
- History of disease which may preclude the participant from participation, or which may interfere with outcome measure testing or test results.
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- Incapable of performing visual function testing (e.g., FST testing) for reasons other than poor vision.
- Any absolute contraindication to a course of oral steroids.
- Any other condition that would not allow the potential participant to complete follow-up examinations during the study and, in the opinion of the Investigator, makes the potential participant unsuitable for the study.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Retina Foundation of the Southwest
Dallas, Texas, 75231
Martin Klein, 214-363-3911, mklein@retinafoundation.org
Mark Penessi, MD
- Recruiting
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania, 19104
Mariejel Weber, +12156626396, mariejel.weber@pennmedicine.upenn.edu
Tomas Aleman, MD
About this study
Official title: An Open Label, Dose Exploration, Safety and Tolerability Study of a Subretinal Injection of an OPGx-001 Gene Vector to Participants With LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) With OCncurrent Non-Interventional Follow-Up of Untreated Patients
The goals of this clinical trial are assess the natural course of LCA5-IRD over 6 months and to evaluate the safety and preliminary efficacy of subretinal gene therapy with OPGx-001 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene. Funding Source- FDA Office of Orphan Products Development (OOPD).
Read the detailed description
This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating untreated patients for 6 months and with three doses of OPGx-001 for the treatment of LCA5-IRD.
Enrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC).
Concurrently, 16 untreated patients will be assessed for 6 months prior to treatment to study the natural course of LCA5-IRD.
- Conditions
- LCA5
- Being tested
- AAV8.hLCA5
- Keywords
- LCA, Retinal Degeneration, IRD, adeno associated virus, gene therapy, LCA5
- Medical subject headings
- Retinal Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV8.hLCA5Biological
Adeno-associated virus vector expressing human LCA5 gene
| Study group | Role | What they receive |
|---|---|---|
| Dose Group 1 | Experimental | A single, unilateral, subretinal injection of low dose (1E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a low dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents). Receives: Biological: AAV8.hLCA5 |
| Dose Group 2 | Experimental | A single, unilateral, subretinal injection of an intermediate dose (3E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of an intermediate dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents). Receives: Biological: AAV8.hLCA5 |
| Dose Group 3 | Experimental | A single, unilateral, subretinal injection of high dose (1E11 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a high dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents). Receives: Biological: AAV8.hLCA5 |
| Part B Observational | No intervention | Part B will occur concurrently with Dose Groups 1-3. Sixteen patients will be assessed for 6 months to assess the natural course of LCA5-IRD, then will be treated with OPGx-001 which will be described in a future protocol amendment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose Limiting Toxicities
Number of DLT events
Measured: 2 years
Number of adverse events related to OPGx-001
Number of AEs related to IP
Measured: 2 years
Incidence of adverse events related to OPGx-001
Incidence of AEs related to IP
Measured: 2 years
Severity of adverse events related to OPGx-001
Severity of AEs related to IP
Measured: 2 years
Number of procedure-related adverse events
Number of AEs related to IP administration
Measured: 2 years
Incidence of procedure-related adverse events
Incidence of AEs related to IP administration
Measured: 2 years
Severity of procedure-related adverse events
Severity of AEs related to IP administration
Measured: 2 years
Assessment of cross-sectional spectral domain optical coherence tomography images
Qualitative Assessment of SD-OCT image
Measured: 2 years
Assessment of Natural course of LCA5-IRD
Change from baseline in MLoMT
Measured: 6 months
Assessment of Natural course of LCA5-IRD
Change from baseline in FST
Measured: 6 months
Assessment of Natural course of LCA5-IRD
Change from baseline in BCVA
Measured: 6 months
Assessment of Natural course of LCA5-IRD
Change from baseline in FCP/Microperimetry
Measured: 6 months
Assessment of Natural course of LCA5-IRD
Change from baseline in SD-OCT
Measured: 6 months
Assessment of Natural course of LCA5-IRD
Change from baseline in pupillometry
Measured: 6 months
Assessment of Natural course of LCA5-IRD
Number of adverse events
Measured: 6 months
Secondary outcomes (4)
Change from baseline over time in Multi-luminance Orientation and Mobility Test
Number of objects identified
Measured: 2 years
Change from baseline over time in Dark-adapted full-field sensitivity testing
FST
Measured: 2 years
Change from baseline over time in best corrected visual acuity (BCVA)
Measured using LogMAR scale
Measured: 2 years
Change from baseline over time in visual functioning questionnaire
Assessed by the Modified National Eye Institute Visual Functioning Questionnaire
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2022
- Study start15 Jun 2023
- Primary completion15 Jun 2028 (estimated)
- Study completion15 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LCA5Studies 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Enrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC). Concurrently, 16 untreated patients will be assessed for 6 months prior to treatment to study the natural course of LCA5-IRD.
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Opus Genetics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Pennsylvania
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05616793
- Sponsor's protocol ID
- OPGx-LCA5-1001
- Other IDs
- FD-R-008174
- Status last verified
- Feb 2026
- First submitted
- 7 Nov 2022
- Last updated
- 19 Feb 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 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Dose Exploration, Safety and Tolerability Study of a Subretinal Injection of an OPGx-001 Gene Vector to Participants With LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) With OCncurrent Non-Interventional Follow-Up of Untreated Patients
- ClinicalTrials.gov ID
- NCT05616793
- Acronym / sponsor ID
- OPGx-LCA5-1001
- Conditions
- LCA5
- Keywords
- LCA, Retinal Degeneration, IRD, adeno associated virus, gene therapy, LCA5
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Opus Genetics, IncIndustry (pharma, biotech, devices)
- Collaborators
- University of Pennsylvania
- Study start
- 15 Jun 2023 (actual)
- Primary completion
- 15 Jun 2028 (estimated)
- Study completion
- 15 Jun 2028 (estimated)
- First posted
- 15 Nov 2022 (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 goals of this clinical trial are assess the natural course of LCA5-IRD over 6 months and to evaluate the safety and preliminary efficacy of subretinal gene therapy with OPGx-001 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene. Funding Source- FDA Office of Orphan Products Development (OOPD).
Detailed description
This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating untreated patients for 6 months and with three doses of OPGx-001 for the treatment of LCA5-IRD.
Enrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC).
Concurrently, 16 untreated patients will be assessed for 6 months prior to treatment to study the natural course of LCA5-IRD.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Enrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC). Concurrently, 16 untreated patients will be assessed for 6 months prior to treatment to study the natural course of LCA5-IRD.
| Arm | Type | Receives |
|---|---|---|
| Dose Group 1 | Experimental | Biological: AAV8.hLCA5A single, unilateral, subretinal injection of low dose (1E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a low dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents). |
| Dose Group 2 | Experimental | Biological: AAV8.hLCA5A single, unilateral, subretinal injection of an intermediate dose (3E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of an intermediate dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents). |
| Dose Group 3 | Experimental | Biological: AAV8.hLCA5A single, unilateral, subretinal injection of high dose (1E11 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a high dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents). |
| Part B Observational | No intervention | –Part B will occur concurrently with Dose Groups 1-3. Sixteen patients will be assessed for 6 months to assess the natural course of LCA5-IRD, then will be treated with OPGx-001 which will be described in a future protocol amendment. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Are willing and able to provide written informed consent (ICF) and, where appropriate, willing to sign an assent prior to any study procedures.
- Are willing to adhere to the clinical protocol and able to perform testing procedures.
- In part A participants must be 13 years of age or older at consent, for Part B, participants must be 4 years of age or older at consent with the ability to conduct the MLoMT.
- Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (historic testing up to 15 years from date of consent can be considered).
- Visual acuity: BCVA < 20/80 on the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart (modified for low vision participants) in the eye to be treated
Key exclusion criteria (9 listed)
- Women who are pregnant or individuals (women of childbearing potential and men) unwilling to use effective contraception for the duration of the study, including barrier methods for the first year after investigational product (IP) administration (Part A only).
- Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery. This includes individuals who are immunocompromised.
- History of intraocular surgery for either eye within 6 months prior to planned IP administration (Part A only).
- Have previously received gene therapy.
- Have used any investigational drug or device within 90 days or 5 estimated half-lives of treatment, whichever is longer or plan to participate in another study of drug or device during the study period.
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 |
|---|---|---|
| AAV8.hLCA5Adeno-associated virus vector expressing human LCA5 gene | Biological | Dose Group 1, Dose Group 2, Dose Group 3 |
Primary outcome
Incidence of Dose Limiting Toxicities
Time frame: 2 years
Number of DLT events
Number of adverse events related to OPGx-001
Time frame: 2 years
Number of AEs related to IP
Incidence of adverse events related to OPGx-001
Time frame: 2 years
Incidence of AEs related to IP
Severity of adverse events related to OPGx-001
Time frame: 2 years
Severity of AEs related to IP
Number of procedure-related adverse events
Time frame: 2 years
Number of AEs related to IP administration
Incidence of procedure-related adverse events
Time frame: 2 years
Incidence of AEs related to IP administration
Severity of procedure-related adverse events
Time frame: 2 years
Severity of AEs related to IP administration
Assessment of cross-sectional spectral domain optical coherence tomography images
Time frame: 2 years
Qualitative Assessment of SD-OCT image
Assessment of Natural course of LCA5-IRD
Time frame: 6 months
Change from baseline in MLoMT
Assessment of Natural course of LCA5-IRD
Time frame: 6 months
Change from baseline in FST
Assessment of Natural course of LCA5-IRD
Time frame: 6 months
Change from baseline in BCVA
Assessment of Natural course of LCA5-IRD
Time frame: 6 months
Change from baseline in FCP/Microperimetry
Assessment of Natural course of LCA5-IRD
Time frame: 6 months
Change from baseline in SD-OCT
Assessment of Natural course of LCA5-IRD
Time frame: 6 months
Change from baseline in pupillometry
Assessment of Natural course of LCA5-IRD
Time frame: 6 months
Number of adverse events
4 secondary outcomes
Change from baseline over time in Multi-luminance Orientation and Mobility Test
Time frame: 2 years
Change from baseline over time in Dark-adapted full-field sensitivity testing
Time frame: 2 years
Change from baseline over time in best corrected visual acuity (BCVA)
Time frame: 2 years
Change from baseline over time in visual functioning questionnaire
Time frame: 1 year
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 19 Feb 2026.
- Individual participant dataSharing planned: No
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.
2 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 AAV8.hLCA5 in people with LCA5, run by Opus Genetics, Inc at 2 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 8 inclusion and 9 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 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 Tomas Aleman, M.D. (1 (215) 662-6396, 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?
Incidence of Dose Limiting Toxicities (time frame: 2 years). The study lists 15 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 19 Feb 2026.