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Trial record 24 of 327 for:    "Eye Diseases, Hereditary" OR "Peters plus syndrome"

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

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ClinicalTrials.gov Identifier: NCT03328130
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : November 14, 2017
Sponsor:
Information provided by (Responsible Party):
Horama S.A.

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 three consecutive cohorts of patients, will be recruited.

Condition or disease Intervention/treatment Phase
Retinitis Pigmentosa Biological: AAV2/5-hPDE6B Phase 1 Phase 2

Detailed Description:

Retinitis pigmentosa (RP) is a disease where part of the eye (the retina) is degenerating over time. Patients initially present with night blindness, and later in life experience loss of central vision which leads to blindness. RP is a highly variable disorder with some patients developing symptomatic visual loss in childhood whereas others remain asymptomatic until mid-adulthood. There are no treatments available.

This study focuses on the form of RP caused by mutations (modifications) in the genetic information necessary to make the protein called rod cGMP phosphodiesterase 6 β subunit (or PDE6β). Clinical diagnosis is made by function tests of the eye and confirmed using a specific method called molecular testing to verify that the PDE6B gene is not correct.

This study uses a gene therapy vector inspired from an adeno-associated virus (AAV) called AAV2/5-hPDE6B. This vector intends to supply to the target cells the PDE6B therapeutic gene that is not functioning properly in the cell. The AAV parts of the gene therapy vector work as a vehicle to deliver the normal human PDE6B gene into the cells of the retina.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Three successive cohorts separated by DSMC assessments
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of a Unilateral Subretinal Administration of HORA-PDE6B in Patients With Retinitis Pigmentosa Harbouring Mutations in the PDE6B Gene Leading to a Defect in PDE6ß Expression
Actual Study Start Date : November 6, 2017
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Experimental: Cohort 1 - Low Dose
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
Subretinal administration in one eye

Experimental: Cohort 2 - High Dose
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
Subretinal administration in one eye

Experimental: Cohort 3 - Confirmatory Dose
Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the confirmatory dose.
Biological: AAV2/5-hPDE6B
Subretinal administration in one eye




Primary Outcome Measures :
  1. Incidence of ocular and non-ocular adverse events [ Time Frame: 1 year + 2 years follow-up ]

Secondary Outcome Measures :
  1. Improvement in visual function [ Time Frame: 1 year + 2 years follow-up ]
    Improvement in visual function as assessed by mobility test

  2. Improvement in visual fields [ Time Frame: 1 year + 2 years follow-up ]
    Improvement in visual fields as assessed by visual fields measurements

  3. Improvement in visual function [ Time Frame: 1 year + 2 years follow-up ]
    Improvement in visual function as assessed by reading speed

  4. Improvement in Quality of Life [ Time Frame: 1 year + 2 years follow-up ]
    Quality of life will be measured by Quality of Life questionnaire National Eye Institute Visual Function Questionnaire (NEI VFQ-25)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Clinical and molecular diagnosis of retinitis pigmentosa caused by defect in PDE6B gene without other syndromic manifestations
  • Aged 18 years or older
  • Ability to give informed consent

Key Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03328130


Contacts
Contact: Jean-Yves Deslandes 33 (0)1 81 69 87 72 jy.deslandes@horama.fr
Contact: Séverine Marconi 33 (0)6 22 73 26 34 s.marconi@horama.fr

Locations
France
Clinique Ophtalmologique, CHU de Nantes Recruiting
Nantes, France, 44093
Contact: Pierre Lebranchu       pierre.lebranchu@chu-nantes.fr   
Sponsors and Collaborators
Horama S.A.

Publications of Results:
Responsible Party: Horama S.A.
ClinicalTrials.gov Identifier: NCT03328130     History of Changes
Other Study ID Numbers: HORA-PDE6B-001
2016-001429-16 ( EudraCT Number )
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: November 14, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Horama S.A.:
Eye Diseases, Hereditary
Adeno-associated virus
AAV
Retinitis Pigmentosa
PDE6B
Gene Therapy
Gene Transfer
Retinal Dystrophy
Eye Diseases
Vision Disorders
Retinal Diseases
Retinal Degeneration

Additional relevant MeSH terms:
Retinitis
Retinitis Pigmentosa
Cone-Rod Dystrophies
Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn