What is the mechanism of action of this treatment?

Gene therapy for Retinitis Pigmentosa (RP) involves replacing or repairing defective genes responsible for the disease. This is achieved by using viral vectors to deliver functional copies of the gene or to edit the existing gene in retinal cells. The primary goal is to halt or slow the degeneration of photoreceptor cells, thereby preserving vision. This approach is significant for RP patients as it targets the underlying genetic cause, offering the potential for long-term benefits and improved quality of life.

What side effects are associated with this type of intervention?

Gene therapy for Retinitis Pigmentosa, such as the OCU400 trial, aims to replace or repair defective genes. Known side effects of gene therapy can include immune reactions, inflammation, and potential off-target effects where the therapy might affect unintended genes. Other common treatments for RP, like vitamin A supplementation, can lead to liver toxicity and hypervitaminosis A if not monitored properly. Overall, while gene therapy holds promise, it requires careful monitoring for adverse effects.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved gene therapies for Retinitis Pigmentosa. However, gene therapy has shown promise in clinical trials, such as the use of self-complementary AAV vectors to restore visual function in models of Rpe65 deficiency. The OCU400 trial is exploring gene therapy for Retinitis Pigmentosa and Leber Congenital Amaurosis, aiming to replace or repair defective genes, which is a similar approach to ongoing research in gene therapy for retinal diseases.

What other types of research exist?

Promising novel alternatives to OCU400 for Retinitis Pigmentosa patients include: 1) CRISPR-Cas9 gene editing, which aims to correct genetic mutations directly; 2) Stem cell therapy, particularly the use of induced pluripotent stem cells (iPSCs) to regenerate retinal cells; 3) Antisense oligonucleotide (ASO) therapy, which targets and modifies RNA to reduce the impact of genetic mutations; and 4) Optogenetics, which involves introducing light-sensitive proteins into retinal cells to restore vision. These therapies are in various stages of research and clinical trials and offer potential new avenues for treatment.

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Gene Therapy

OCU400 for Retinitis Pigmentosa (OCU400 Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Ocugen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Timeline

Screening 2 days

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests OCU400, an eye injection, in patients with specific genetic mutations causing RP and LCA. The treatment aims to correct faulty genes to prevent vision loss.

Who is the study for?

This trial is for adults over 18 with certain genetic mutations causing retinitis pigmentosa or Leber Congenital Amaurosis. Participants must have a specific level of visual impairment and be able to perform a mobility test in low light. They can't join if they're pregnant, breastfeeding, have had recent eye surgery, previous gene therapy, or any condition that might affect the study results.

What is being tested?

The trial tests three doses (low, medium, high) of OCU400 on patients with retinitis pigmentosa and Leber Congenital Amaurosis to evaluate its safety and effectiveness. It includes an initial phase followed by a natural history study across multiple centers involving up to 124 subjects.

What are the potential side effects?

Potential side effects are not explicitly listed but may include typical risks associated with subretinal injections such as eye irritation, infection risk post-surgery, inflammation inside the eye or vision changes due to the procedure.

Timeline

Screening ~ 2 days0 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 2 days

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 2 days for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Serious adverse events (SAEs)

Study Drug-related adverse events (SDAE)

Treatment-Emergent adverse events (TEAEs)

Secondary study objectives

Best-corrected visual acuity (BCVA)

Indirect ophthalmoscopy

Intraocular pressure (IOP)

+5 more

Other study objectives

Changes in ellipsoid zone width/length on wide-field 20° SD-OCT

Contrast sensitivity

Full Field Electroretinogram

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Active Control

Group I: Pediatric ArmExperimental Treatment1 Intervention

Pediatric subjects will receive the medium dose concentration and will have subjects with RP and LCA

Group II: Cohort 3 (High Dose)Experimental Treatment1 Intervention

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation, RHO mutations subgroup and LCA patients with CEP290

Group III: Cohort 2 (Mid Dose)Experimental Treatment1 Intervention

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation or RHO mutations subgroup

Group IV: Cohort 1 (Low Dose)Experimental Treatment1 Intervention

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation or RHO mutations subgroup

Group V: Adult ArmExperimental Treatment1 Intervention

Following DSMB confirmation, adult LCA subjects with CEP290 mutation will receive a medium dose concentration of OCU400.

Group VI: Natural History Study (OCU400-104)Active Control1 Intervention

A Prospective and Retrospective Natural History Study of RP and LCA: This is an observatory study for the prospective natural history of RP and LCA in adult and pediatric subjects. The study will also collect and review retrospective data and ophthalmology examination of natural history and progression of disease for all subjects starting with earliest timepoint on or after the date of their diagnosis of RP or LCA. Subjects will be seen up to a total of four times during the 12 months of the Observational Period, at baseline, 3 months, 6 months and 12 months. A total of up to 100 subjects will be enrolled in the study, including: Approximately 76 newly enrolled subjects consisting of 50 adult RP subjects 6 adult LCA subjects 20 pediatric RP/LCA subjects. Up to 24 subjects that reconsent from the OCU400-101 study (subjects from OCU400-101 will provide data on their untreated eye)

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Gene therapy for Retinitis Pigmentosa (RP) involves replacing or repairing defective genes responsible for the disease. This is achieved by using viral vectors to deliver functional copies of the gene or to edit the existing gene in retinal cells. The primary goal is to halt or slow the degeneration of photoreceptor cells, thereby preserving vision. This approach is significant for RP patients as it targets the underlying genetic cause, offering the potential for long-term benefits and improved quality of life.

Restoration of vision in the pde6β-deficient dog, a large animal model of rod-cone dystrophy.