OCU410ST for Stargardt Disease

(GARDian3 Trial)

Recruiting at 14 trial locations

Overseen By Mahvish Tafseer, MD, MPH

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ocugen

Must not be taking: Retroviral therapy

Disqualifiers: Gene therapy, Cell therapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Stargardt disease, a genetic eye disorder that causes vision loss. The study tests a treatment called OCU410ST, delivered through a single injection into the eye. Researchers aim to determine if this treatment can slow or stop the progression of vision loss. Suitable candidates for this trial have a confirmed diagnosis of Stargardt disease and noticeable vision problems. Participants will either receive the treatment or join a control group that does not, allowing for result comparison. As a Phase 2, Phase 3 trial, this study evaluates the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on retroviral therapy, you may need to stop as it could interfere with the investigational product.

Is there any evidence suggesting that OCU410ST is likely to be safe for humans?

Research has shown that OCU410ST is generally safe for people. In earlier studies, participants tolerated it well, with most experiencing no problems. A group of experts reviewed the safety data and approved further studies, finding no serious safety issues. Another report noted that the treatment slowed down Stargardt disease, a genetic eye condition, without causing major side effects. This suggests it could be both effective and safe for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

OCU410ST is unique because it’s a gene therapy designed to treat Stargardt disease, a condition that currently has no FDA-approved treatments. Unlike other treatment approaches that might focus on managing symptoms, OCU410ST delivers a specific gene directly into the retina through a subretinal injection. This innovative delivery method has the potential to address the root cause of the disease by targeting the genetic defects responsible for Stargardt disease. Researchers are excited about this because it could offer a more effective, long-term solution compared to managing symptoms with vitamins or lifestyle changes.

What evidence suggests that OCU410ST might be an effective treatment for Stargardt Disease?

Research has shown that OCU410ST, which participants in this trial may receive, might help treat Stargardt Disease by slowing the growth of eye lesions. In earlier studies, patients who took OCU410ST experienced 84% slower lesion growth compared to those without treatment. This suggests that OCU410ST could help maintain vision over time. The treatment targets specific genes in the eye, potentially restoring balance and improving eye health. Early trial results have been promising, indicating that OCU410ST could be a helpful therapy for people with Stargardt Disease. ^{2 3 4 6 7}

Who Is on the Research Team?

Murthy Chavali, MD, Ph.D.

Principal Investigator

Ocugen., Inc.

Are You a Good Fit for This Trial?

This clinical trial is for individuals aged 18-65 with Stargardt Disease, specifically those who have a vision acuity of 50 letters or less on the ETDRS chart. Participants must have confirmed genetic mutations in ABCA4 and evidence of macular lesions consistent with the disease. They should also have some remaining retinal layer detectable by OCT imaging.

Inclusion Criteria

I have two harmful mutations in my ABCA4 gene.

Detectable outer nuclear layer (ONL) in the macular region tomography (SD-OCT)

I have a diagnosis of Stargardt Disease affecting my eyes.

Exclusion Criteria

I cannot have eye injections or be put under anesthesia due to health reasons.

Concurrent retroviral therapy that would inactivate the investigational product

I have never had gene or cell therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Open-label, dose-ranging/dose escalation study with a 3+3 design enrolling up to 18 subjects

12 months

Multiple visits for dose administration and monitoring

Phase 2 Treatment

Randomized, dose-expansion cohort with subjects receiving subretinal injections of OCU410ST

12 months

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits for safety and efficacy assessments

What Are the Treatments Tested in This Trial?

Interventions

• OCU410ST

Trial Overview The study tests OCU410ST's safety and effectiveness for treating Stargardt Disease. It's a two-phase trial involving up to 42 participants across multiple centers, aiming to see how well this treatment works and if it's safe.

How Is the Trial Designed?

Group I: Phase 2/3 Randomized Treatment Arm Experimental Treatment 1 Intervention

Subjects will receive a single subretinal injection of 200uL OCU410ST in concentration of 1.5 x 10E11vg/mL

Group II: Phase 2/3 Randomized Control Arm Active Control 1 Intervention

Subjects will not receive any active study intervention

OCU410ST is already approved in United States, European Union for the following indications:

Approved in United States as OCU410ST for:

• None - Orphan Drug Designation granted for ABCA4-associated retinopathies including Stargardt, RP19, and CORD3

Approved in European Union as OCU410ST for:

• None - Orphan Medicinal Product Designation granted for ABCA4-associated retinopathies including Stargardt disease

Who Is Running the Clinical Trial?

Ocugen

Lead Sponsor

Trials

12

Recruited

1,100+

Published Research Related to This Trial

In a study of 12 subjects from two related families with Stargardt disease, significant clinical variation was observed, with different family members exhibiting distinct phenotypes and progression of the disease.

The findings suggest that Stargardt disease may have a grading pattern based on age-related changes in visual function, indicating a need for more parameters to classify the disease effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical polymorphism of stargardt disease in a large consanguineous tunisian family; implications for nosology. El Matri, L., Ouechtati, F., Chebil, A., et al.[2021]

Over a nine-year study of a large Tunisian family with Stargardt disease, all seven patients progressed to the same advanced phenotype (phenotype 3), indicating a consistent and progressive nature of the disease despite initial phenotypic variations.

Genetic analysis revealed two mutations in the ABCA4 gene, but these variations did not affect the end-stage progression of the disease, suggesting that the severity of Stargardt disease may be more influenced by other factors than just specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenotypic Progression of Stargardt Disease in a Large Consanguineous Tunisian Family Harboring New ABCA4 Mutations. Falfoul, Y., Habibi, I., Turki, A., et al.[2020]

In a study of 12 patients with recessive Stargardt disease (STGD1), a distinct phenotype was observed characterized by advanced outer retinal degeneration, leading to a pale fundus appearance due to scleral exposure after approximately 50 years of disease progression.

The patients exhibited severe visual impairment, with best-corrected visual acuity ranging from 20/400 to hand motion, and significant loss of outer retinal structures was confirmed through imaging techniques, indicating a severe impact on retinal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Scleral Exposure: A Degenerative Outcome of End-Stage Stargardt Disease. Lee, W., Zernant, J., Nagasaki, T., et al.[2021]

Dual AAV vectors have been developed to deliver the ABCA4 gene effectively, overcoming the packaging limitations of traditional AAV vectors, which can only hold about 5 kb of genetic material.

In tests on both mouse and pig photoreceptors, these dual AAV vectors successfully rescued the retinal phenotype in Abca4-/- mice, demonstrating their potential as a gene therapy for Stargardt disease (STGD1).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual AAV Vectors for Stargardt Disease. Trapani, I.[2019]

The AAV5-hGRK1 vector effectively targets both rod and cone photoreceptors in nonhuman primates, demonstrating its potential for gene therapy in retinal diseases.

The study confirmed the safety of AAV5-hGRK1, with no significant pathology observed post-injection and undetectable neutralizing antibodies, indicating a favorable profile for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The human rhodopsin kinase promoter in an AAV5 vector confers rod- and cone-specific expression in the primate retina. Boye, SE., Alexander, JJ., Boye, SL., et al.[2021]

The study demonstrated that a hybrid AAV dual vector system effectively delivered the full-length ABCA4 gene in a mouse model of Stargardt disease, leading to proper localization of the ABCA4 protein in photoreceptor cells.

Treatment with this hybrid vector significantly reduced the accumulation of toxic lipofuscin compounds in the retina, indicating its potential as a safe and therapeutic approach for addressing the underlying cause of Stargardt disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual ABCA4-AAV Vector Treatment Reduces Pathogenic Retinal A2E Accumulation in a Mouse Model of Autosomal Recessive Stargardt Disease. Dyka, FM., Molday, LL., Chiodo, VA., et al.[2020]

In a study of 51 patients with early-onset Stargardt disease, the average age of onset was 7.2 years, and visual acuity declined significantly over time, with profound chorioretinal atrophy developing as the disease progressed.

Genetic screening revealed that 37 out of 44 patients had two mutations in the ABCA4 gene, indicating a strong genetic basis for this severe form of retinal degeneration, which often presents with minimal initial abnormalities on examination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-onset stargardt disease: phenotypic and genotypic characteristics. Lambertus, S., van Huet, RA., Bax, NM., et al.[2022]

The study enrolled 15 patients with Stargardt disease type 4, all carrying variants in the PROM1 gene, to investigate the natural history of the disease over a 2-year period with regular follow-ups.

At baseline, 34.5% of the patients' eyes showed areas of definitely decreased autofluorescence, indicating retinal damage, with an average lesion size of 3.2 mm², which will help in understanding disease progression and may inform future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1). Strauss, RW., Muñoz, B., Ahmed, MI., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05956626

Study Details | NCT05956626 | A Phase 2/3 Trial to Assess ... The role of hRORA in regulating these gene pathways strongly suggests OCU410ST could restore homeostasis in the eye and thereby serve as a therapeutic candidate ...

2. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2808863

Safety and Efficacy of OCU410ST for the Treatment of ... - IOVS Efficacy data from 3 evaluable subjects (2 low-dose and 1 medium-dose) showed 84% slower lesion growth in study eyes (mean ± SEM, 0.12 ± 0.36 mm2) compared to ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05956626/a-phase-2-3-trial-to-assess-the-efficacy-and-safety-of-ocu410st-for-stargardt-disease

A Phase 2/3 Trial to Assess the Efficacy and Safety ... A Phase 2/3 Trial to Assess the Efficacy and Safety of OCU410ST for Stargardt Disease ; Condition. Geographic Atrophy. Macular Degeneration.

4. fightingblindness.org fightingblindness.org/news/ocugen-launches-phase-2-3-clinical-trial-for-stargardt-disease-gene-modifier-therapy-2620

Ocugen Launches Phase 2/3 Clinical Trial for Stargardt ... The company reported encouraging safety and efficacy results for six patients in its Phase 1/2 clinical trial for OCU410ST. scroll to top.

5. ir.ocugen.com ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-first-patient-dosed-phase-23-gardian3

Ocugen, Inc. Announces First Patient Dosed in Phase 2/3 ... The encouraging Phase 1 results give us confidence that OCU410ST could meaningfully slow disease progression and help preserve vision. This ...

6. ir.ocugen.com ir.ocugen.com/news-releases/news-release-details/data-and-safety-monitoring-board-approves-initiation-phase-2

Press Release - Investors - Ocugen “The DSMB has recommended moving forward with Phase 2 enrollment, as safety data indicates that OCU410ST appears to be safe and well-tolerated ...

7. ir.ocugen.com ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-positive-scientific-advice-european-0

Press Release - Investors - Ocugen EMA provided this opinion based on safety and tolerability that OCU410ST demonstrated in the Phase 1 GARDian trial, including 48% slower lesion ...