Safety and Efficacy Study in Patients With Retinitis Pigmentosa Due to Mutations in PDE6B Gene

NCT03328130 | Terminated Phase 1 DMC

• 2 other identifiers: HORA-PDE6B-0012016-001429-16
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a Phase I/II, monocentric, open-label, dose-ranging safety and efficacy gene therapy intervention by subretinal administration of AAV2/5-hPDE6B. At least twelve patients 18 years of age or older, within four consecutive cohorts of patients, will be recruited. Then at least four patients 13 years of age or older, within a fifth cohort, will be recruited.

Conditions

Retinitis Pigmentosa

Keywords

Adeno-associated virus; AAV; Retinitis Pigmentosa; PDE6B; Gene Therapy; Gene Transfer; Retinal Dystrophy; Eye Diseases; Vision Disorders; Eye Diseases, Hereditary; Retinal Diseases; Retinal Degeneration

Outcome Measures

Primary Outcomes (1)

• Incidence of ocular and non-ocular adverse events

  1 year + 4 years follow-up

Secondary Outcomes (4)

• Improvement in visual function

  1 year + 4 years follow-up

• Improvement in visual fields

  1 year + 4 years follow-up

• Improvement in visual function

  1 year + 4 years follow-up

• Improvement in Quality of Life

  1 year + 4 years follow-up

Study Arms (5)

Cohort 1 - Low Dose

EXPERIMENTAL

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the lowest dose. Dose-escalation will be performed after DSMC assessment.

Biological: AAV2/5-hPDE6B

Cohort 2a - Medium Dose

EXPERIMENTAL

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the medium dose. Confirmatory dose will be determined after DSMC assessment.

Biological: AAV2/5-hPDE6B

Cohort 2b - High Dose

EXPERIMENTAL

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the highest dose. Confirmatory dose will be determined after DSMC assessment.

Biological: AAV2/5-hPDE6B

Cohort 3 - High Dose (confirmatory cohort)

EXPERIMENTAL

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the confirmatory dose.

Biological: AAV2/5-hPDE6B

Cohort 4 - High Dose - 13 years old or older population

EXPERIMENTAL

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the confirmatory dose.

Biological: AAV2/5-hPDE6B

Interventions

AAV2/5-hPDE6B BIOLOGICAL

Subretinal administration in one eye

Cohort 1 - Low Dose; Cohort 2a - Medium Dose; Cohort 2b - High Dose; Cohort 3 - High Dose (confirmatory cohort); Cohort 4 - High Dose - 13 years old or older population

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical and molecular diagnosis of retinitis pigmentosa caused by defect in PDE6B gene without other syndromic manifestations
• Aged above 13 years
• Ability to give informed consent

You may not qualify if:

• Previous ocular surgery or thermal laser within 6 months before the surgery
• Lens opacities or obscured ocular media upon recruitment such reliable evaluation or grading of the posterior segment cannot be performed
• Known serious allergies to the fluorescein dye used in angiography, to the mydriatic, steroidal and non-steroidal eye drops
• Participation in another clinical trial with an investigational agent
• Enrolled or being enrolled in another gene therapy clinical trial
• Active, extraocular infection requiring the prolonged or chronic use of antimicrobial agents
• Chronic medical conditions, cancer
• Abnormal laboratory values
• On immunosuppressive therapy

Sponsors & Collaborators

• eyeDNA Therapeutics: lead

Study Sites (1)

Clinique Ophtalmologique, CHU de Nantes

Nantes, 44093, France

Location

Related Publications (3)

• Petit L, Lheriteau E, Weber M, Le Meur G, Deschamps JY, Provost N, Mendes-Madeira A, Libeau L, Guihal C, Colle MA, Moullier P, Rolling F. Restoration of vision in the pde6beta-deficient dog, a large animal model of rod-cone dystrophy. Mol Ther. 2012 Nov;20(11):2019-30. doi: 10.1038/mt.2012.134. Epub 2012 Jul 24.

  PMID: 22828504 RESULT

• Pichard V, Provost N, Mendes-Madeira A, Libeau L, Hulin P, Tshilenge KT, Biget M, Ameline B, Deschamps JY, Weber M, Le Meur G, Colle MA, Moullier P, Rolling F. AAV-mediated Gene Therapy Halts Retinal Degeneration in PDE6beta-deficient Dogs. Mol Ther. 2016 May;24(5):867-76. doi: 10.1038/mt.2016.37. Epub 2016 Feb 9.

  PMID: 26857842 RESULT

• Palmowski-Wolfe A, Stingl K, Habibi I, Schorderet D, Tran HV. Novel PDE6B Mutation Presenting with Retinitis Pigmentosa - A Case Series of Three Patients. Klin Monbl Augenheilkd. 2019 Apr;236(4):562-567. doi: 10.1055/a-0811-5480. Epub 2019 Jan 15.

  PMID: 30646425 DERIVED

MeSH Terms

Conditions

Retinitis Pigmentosa; Retinal Dystrophies; Eye Diseases; Vision Disorders; Eye Diseases, Hereditary; Retinal Diseases; Retinal Degeneration

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

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

Model Details: Five successive cohorts separated by DSMC assessments

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: November 1, 2017
• Study Start: November 6, 2017
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)