Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03328130
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : June 6, 2023
Sponsor:
Information provided by (Responsible Party):
Coave Therapeutics

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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 to 25 years of age, within a fifth cohort, 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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Five 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 : December 2029
Estimated Study Completion Date : December 2029

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 2a - Medium Dose
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
Subretinal administration in one eye
Experimental: Cohort 2b - 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 - High Dose (confirmatory cohort)
Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the confirmatory dose.
 Biological: AAV2/5-hPDE6B
Subretinal administration in one eye
Experimental: Cohort 4 - High Dose - 13-25 years old population
Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the confirmatory dose.
 Biological: AAV2/5-hPDE6B
Subretinal administration in one eye


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Incidence of ocular and non-ocular adverse events [ Time Frame: 1 year + 4 years follow-up ]

Secondary Outcome Measures :
  1. Improvement in visual function [ Time Frame: 1 year + 4 years follow-up ]
    Improvement in visual function as assessed by mobility test

  2. Improvement in visual fields [ Time Frame: 1 year + 4 years follow-up ]
    Improvement in visual fields as assessed by visual fields measurements

  3. Improvement in visual function [ Time Frame: 1 year + 4 years follow-up ]
    Improvement in visual function as assessed by reading speed

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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   13 Years and older   (Child, 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 above 13 years (for cohort #4 only: 13 to 25 years old)
  • 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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Layout table for location contacts
Contact: Medical Director / Chief Development Officer, MD 01 81 69 87 70 contact@coavetx.com

Locations
Layout table for location information
France
Clinique Ophtalmologique, CHU de Nantes Recruiting
Nantes, France, 44093
Contact: Pierre Lebranchu       pierre.lebranchu@chu-nantes.fr   
Sponsors and Collaborators
Coave Therapeutics
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Coave Therapeutics
ClinicalTrials.gov Identifier: NCT03328130    
Other Study ID Numbers: HORA-PDE6B-001
2016-001429-16 ( EudraCT Number )
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: June 6, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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 Coave Therapeutics:
Adeno-associated virus
AAV
Retinitis Pigmentosa
PDE6B
Gene Therapy
Gene Transfer
 Retinal Dystrophy
Eye Diseases
Vision Disorders
Eye Diseases, Hereditary
Retinal Diseases
Retinal Degeneration
Additional relevant MeSH terms:
Layout table for MeSH terms
Retinitis
Retinitis Pigmentosa
Retinal Diseases
Eye Diseases
 Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn