Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis

NCT05203939 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: OCU400-101
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 7

Brief Summary

This is a Phase 1/2 Study to Assess the Safety and Efficacy of OCU400 in patients with retinitis pigmentosa associated with NR2E3 and RHO mutations and in patients with LCA due to mutation(s) in CEP290 gene (OCU400-101). To document prospective eye pathology in the above subjects Investigators will also conduct a Natural History Study (OCU400-104)i This is a multicenter study, which will be conducted in two phases and will enroll up to a total of 24 subjects in the OCU400-101 and 100 subjects in the OCU400-104 study.

Conditions

Retinitis Pigmentosa; Leber Congenital Amaurosis

Keywords

NR2E3; Rhodopsin; Enhanced S-cone syndrome; Cep290

Outcome Measures

Primary Outcomes (3)

• Study Drug-related adverse events (SDAE)

  Counts, frequencies and percentages of SDAEs. SDAE is a primary adverse event of interest and defined as AEs and SAEs that are direct subjects to the Study Drug only.

  1 year

• Treatment-Emergent adverse events (TEAEs)

  Counts, frequencies and percentages TEAEs. TEAEs are defined as an event that was not present prior to administration of the dose of study drug and present after the dose, or if it represents the exacerbation of an event that was present prior to the dose.

  1 year

• Serious adverse events (SAEs)

  Counts, frequencies and percentages of SAEs including Resulted in Death, Life-threatening, Hospitalization, Disabling/incapacitating, Congenital anomaly or birth defect and medically significant AEs ( AE that did not meet any of the above criteria but could have jeopardized the subject and might have required medical or surgical intervention to prevent one of the outcomes listed above).

  1 year

Secondary Outcomes (8)

• Best-corrected visual acuity (BCVA)

  1 year (Changes from baseline)

• Low-luminance visual acuity (LLVA)

  1 year (Changes from baseline)

• Slit-lamp biomicroscopy

  1 year (Changes from baseline)

• Intraocular pressure (IOP)

  1 year (Changes from baseline)

• Indirect ophthalmoscopy

  1 year (Changes from baseline)

Other Outcomes (8)

• Multi-luminance mobility testing (MLMT)

  1 year (Changes from baseline)

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

  1 year (Changes from baseline)

• Contrast sensitivity

  1 year (Changes from baseline)

Study Arms (8)

Cohort 1 (Low Dose)

EXPERIMENTAL

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

Drug: OCU400 Low Dose

Cohort 2 (Mid Dose)

EXPERIMENTAL

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

Drug: OCU400 Med Dose

Cohort 3 (High Dose)

EXPERIMENTAL

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

Drug: OCU400 High Dose

Pediatric Arm

EXPERIMENTAL

Pediatric subjects will receive the medium dose concentration

Drug: OCU400 Med Dose

Phase 2 (High and Medium Dose)

EXPERIMENTAL

Following DSMB confirmation, adult RP subjects with Biallelic autosomal recessive NR2E3 mutations, autosomal dominant NR2E3 mutations, Autosomal dominant RHO mutations will receive a high dose concentration of OCU400 or LCA patients with CEP290 mutation will receive a medium dose concentration of OCU400.

Drug: OCU400 Med Dose; Drug: OCU400 High Dose

Adult Arm

EXPERIMENTAL

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation, RHO mutations subgroup will receive a high dose concentration of OCU400 and LCA patients with CEP290 will receive a medium dose concentration of OCU400

Drug: OCU400 Med Dose; Drug: OCU400 High Dose

Second Eye Dosing

EXPERIMENTAL

Eligible RP participants will be dosed in the untreated fellow eye with a therapeutic dose used in Phase 3 study of OCU400 (1.0x10E11vg/mL in 250 μl ) and will be followed for an additional 48 weeks.

Drug: OCU400 Second Eye Dosing

Natural History Study (OCU400-104)

NO 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)

Interventions

OCU400 Low Dose DRUG

subretinal injection of up to 1.66×10E10 vg/mL

Cohort 1 (Low Dose)

OCU400 Med Dose DRUG

subretinal injection of up to 3.33×10E10 vg/mL

Adult Arm; Cohort 2 (Mid Dose); Pediatric Arm; Phase 2 (High and Medium Dose)

OCU400 High Dose DRUG

subretinal injection of up to 1.66×10E11 vg/mL

Adult Arm; Cohort 3 (High Dose); Phase 2 (High and Medium Dose)

OCU400 Second Eye Dosing DRUG

subretinal injection of 1.0x10E11vg/mL in 250 μl

Second Eye Dosing

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• Males or females ≥ 18 years of age at the time of informed consent.
• Confirmed genetic diagnosis of biallelic autosomal recessive NR2E3 mutations or autosomal dominant NR2E3 mutation for Subgroup 1 or autosomal dominant RHO mutations for Subgroup 2.
• For the sentinel subject of Cohort 1-3, BCVA ≤ 20/160 in study eye or visual field less than 20° in any meridian, as measured by a III4e isopter or equivalent in study eye.
• For non-sentinel subject, BCVA ≤ 20/50 or visual field less than 20° in any meridian, as measured by a III4e isopter or equivalent in study eye.
• Able to perform a Multi-Luminance Mobility Testing (MLMT) using study eye, but unable to pass the MLMT at 1 lux, the lowest luminance level tested.
• Subject lacks evidence of outer nuclear layer.
• Considered unsuitable for any reason that may either place the subject at increased risk during participation or interfere with the interpretation of the study outcomes by the Investigator, or the Sponsor after reviewing medical, ocular, and psychiatric history, clinical examination, and laboratory evaluation, as determined by the Investigator.
• Previous treatment with a gene therapy or cell therapy product.
• Previous treatment with any investigational drug or device within one year.
• Any contraindications for subretinal injection.
• Cataract Surgery within 3 months. YAG capsulotomy within 1 month. Any other intraocular surgery within 6 months.
• Breast-feeding, pregnancy, sperm donation or inability to practice strict contraception within the Treatment Observation Period.
• Any medical condition with life expectancy \< 6 years.
• Males or females at least 18 years of age at the time of informed consent.
• Clinical diagnosis of LCA and confirmed genetic diagnosis of CEP290 mutation.

Sponsors & Collaborators

• Ocugen: lead

Study Sites (7)

Associated Retina Consultants

Phoenix, Arizona, 85020, United States

Location

Ocugen Site 5 - University of California, San Diego (UCSD) - Shiley Eye Institute

La Jolla, California, 92093, United States

Location

Ocugen Site 3 - Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Ocugen Site 6 - Emory University

Atlanta, Georgia, 30322, United States

Location

Ocugen Site 2 - Casey Eye Institute - OHSU

Portland, Oregon, 97239, United States

Location

Ocugen Site 8 - Mid Atlantic Retina - Wills Eye Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Ocugen Site 1 - Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

Related Links

• Retina World Congress 2024- Meeting Abstract. Title: Safety and Efficacy Results from a Phase 1/2 Clinical Trial of OCU400 Modifier Gene Therapy for Treatment of Retinitis Pigmentosa
• ARVO Annual Meeting 2024- Meeting Abstract: Title: OCU400 Nuclear Hormone Receptor-Based Gene Modifier Therapy: Safety and Efficacy from Phase 1/2 Clinical Trial for Retinitis Pigmentosa Associated with NR2E3 and RHO Mutations
• International Conference on Ophthalmology and Vision Science, Canada- Meeting Abstract: Title: Evaluation of Safety and Efficacy of OCU400 Gene Therapy for Retinitis Pigmentosa: Phase 1/2 Study Results
• American Academy of Ophthalmology (AAO) Annual Meeting- Title: Safety and Efficacy of OCU400 Gene Modifier Therapy for Retinitis Pigmentosa: Phase 1/2 Study Updates

MeSH Terms

Conditions

Retinitis Pigmentosa; Leber Congenital Amaurosis; Night Blindness, Congenital Stationary, Autosomal Dominant 1; Enhanced S-Cone Syndrome; Meckel Syndrome, Type 4

Condition Hierarchy (Ancestors)

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

Study Officials

• Huma Qamar, MD, MPH, CMI

  Ocugen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: January 24, 2022
• Study Start: January 24, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: August 6, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)