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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-24

Study Completion Date

2027-03-31

Brief Summary

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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.

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Detailed Description

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This study will be conducted in two phases enrolling up to 24 subjects. Treated subjects will receive a single subretinal injection of OCU400 in the study eye.

This is a multicenter, open-label, dose-ranging study in two subgroups of subjects with three consecutive cohorts.

A total of 18 adult RP subjects from each of the following subgroups with Biallelic autosomal recessive NR2E3 mutations, autosomal dominant NR2E3 mutations or Autosomal dominant RHO mutations will be selected for dose escalation.

For the Phase I portion of the study, the 3+3 design for sequential dose-escalating cohorts will be used with scheduled 3 dosing levels between 9 and 18 subjects will be used to follow the design.

Up to 3 additional adult LCA patients with CEP290 mutations and at least 1 pediatric LCA subject, will be enrolled in the Phase 2 portion.

Sample Size Justification:

The trial will enroll up to 24 patients (18 adult RP, up to 3 LCA patients, and at least 1 pediatric LCA patient) in both Phase 1 and Phase 2 components.

Participants who meet eligibility criteria will be enrolled and receive a single subretinal injection of OCU400 in one study eye. Participants are considered to have completed this study if they complete the final EOS visit Week 48 (12 months following the IP dose). The study duration will be approximately 58 weeks for each participant and will be followed in Long Term Safety Follow Up for an additional 2 years.

Participants from the Phase 1/2 study who previously received the investigational product (OCU400) in one eye may be eligible to receive OCU400 in the untreated fellow eye, provided they meet the inclusion/exclusion criteria and have completed week 48 follow up visit.

Natural History Study (OCU400-104, 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 the earliest timepoint on or after the date of their diagnosis of RP or LCA. Enrollment for this study has closed.

Conditions

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Retinitis Pigmentosa Leber Congenital Amaurosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 (Low Dose)

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

Group Type EXPERIMENTAL

OCU400 Low Dose

Intervention Type DRUG

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

Cohort 2 (Mid Dose)

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

Group Type EXPERIMENTAL

OCU400 Med Dose

Intervention Type DRUG

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

Cohort 3 (High Dose)

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

Group Type EXPERIMENTAL

OCU400 High Dose

Intervention Type DRUG

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

Pediatric Arm

Pediatric subjects will receive the medium dose concentration

Group Type EXPERIMENTAL

OCU400 Med Dose

Intervention Type DRUG

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

Phase 2 (High and Medium Dose)

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.

Group Type EXPERIMENTAL

OCU400 Med Dose

Intervention Type DRUG

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

OCU400 High Dose

Intervention Type DRUG

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

Adult Arm

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

Group Type EXPERIMENTAL

OCU400 Med Dose

Intervention Type DRUG

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

OCU400 High Dose

Intervention Type DRUG

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

Second Eye Dosing

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.

Group Type EXPERIMENTAL

OCU400 Second Eye Dosing

Intervention Type DRUG

subretinal injection of 1.0x10E11vg/mL in 250 μl

Natural History Study (OCU400-104)

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)

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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OCU400 Low Dose

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

Intervention Type DRUG

OCU400 Med Dose

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

Intervention Type DRUG

OCU400 High Dose

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

Intervention Type DRUG

OCU400 Second Eye Dosing

subretinal injection of 1.0x10E11vg/mL in 250 μl

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Males or females ≥ 18 years of age at the time of informed consent.
2. 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.
3. 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.
4. 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.
5. 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.

1. Males or females at least 18 years of age at the time of informed consent.
2. Clinical diagnosis of LCA and confirmed genetic diagnosis of CEP290 mutation.
3. Best corrected visual acuity (BCVA) equal to or worse than LogMAR +0.7 but equal to or better than LogMAR 3.8 (light perception) in the study eye.
4. Detectable outer nuclear layer in the macular region as determined by spectral-domain optical coherence tomography (SD-OCT).

1. Males or females 6 - 17 years of age (inclusive) at the time of parental permission and/or assent, whichever is applicable.
2. 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.
3. BCVA ≤ 20/32 or visual field less than 20° in any meridian, as measured by a III4e isopter or equivalent in study eye.
4. 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.

1. Males or females 6 - 17 years of age (inclusive) at the time of parental permission and/or assent, whichever is applicable.
2. Clinical diagnosis of LCA and confirmed genetic diagnosis of CEP290 mutation.
3. Best corrected visual acuity (BCVA) equal to or worse than LogMAR +0.7 but equal to or better than LogMAR 3.8 (light perception) in the study eye.
4. Detectable outer nuclear layer in the macular region as determined by spectral-domain optical coherence tomography (SD-OCT).

Exclusion Criteria

1. Subject lacks evidence of outer nuclear layer.
2. 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.
3. Previous treatment with a gene therapy or cell therapy product.
4. Previous treatment with any investigational drug or device within one year.
5. Any contraindications for subretinal injection.
6. Cataract Surgery within 3 months. YAG capsulotomy within 1 month. Any other intraocular surgery within 6 months.
7. Breast-feeding, pregnancy, sperm donation or inability to practice strict contraception within the Treatment Observation Period.
8. Any medical condition with life expectancy \< 6 years.

1. Any symptom of central nervous system involvement/disease that would impact the ability to measure visual function.
2. Considered unsuitable for any reason that may either place the patient at increased risk during participation or interfere with the interpretation of the study safety and efficacy outcomes by the Investigator, after reviewing medical, ocular, and psychiatric history, clinical examination, and laboratory evaluation, as determined by the Investigator.
3. Any contraindications for subretinal injection.
4. Any intraocular surgery within 6 months.
5. Active ocular/intraocular infection (e.g., conjunctivitis, keratitis, scleritis, endophthalmitis).
6. Breast-feeding, pregnancy, sperm donation or inability to practice strict contraception within the Treatment Observation Period.

1. Subject lacks evidence of outer nuclear layer as determined by spectral-domain optical coherence tomography (SD-OCT).
2. 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.
3. Previous treatment with a gene therapy or cell therapy product.
4. Previous treatment with any investigational drug or device within one year.
5. Any contraindications for subretinal injection.
6. Cataract surgery within 3 months. YAG capsulotomy within 1 month. Any other intraocular surgery within 6 months.
7. Breast-feeding, pregnancy, or inability to practice strict contraception within the Treatment Observation Period for subjects of childbearing potential.
8. Active ocular/intraocular infection (e.g., conjunctivitis, keratitis, scleritis, endophthalmitis).
9. Any medical condition with life expectancy \< 6 years.

1. Any symptom of central nervous system involvement/disease that would impact the ability to measure visual function.
2. Considered unsuitable for any reason that may either place the subject at increased risk during participation or interfere with the interpretation of the study safety and efficacy outcomes by the Investigator, after reviewing medical, ocular, and psychiatric history, clinical examination, and laboratory evaluation, as determined by the Investigator.
3. Any contraindications for subretinal injection.
4. Any Intraocular surgery within 6 months.
5. Active ocular/intraocular infection (e.g., conjunctivitis, keratitis, scleritis, endophthalmitis).
6. Breast-feeding, pregnancy, or inability to practice strict contraception within the Treatment Observation Period for subjects of childbearing potential.

Minimum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No