Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65

Sponsor

Nantes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01496040

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the safety and efficacy of the active substance rAAV-2/4.hRPE65 in patients with Leber Congenital Amaurosis or Congenital severe early-onset retinal degeneration associated with RPE65 mutation.

Condition or Disease	Intervention/Treatment	Phase
Leber Congenital Amaurosis	Drug: rAAV2/4.hRPE65	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Official Title:

Prospective Monocentric Open Label Non Randomized Uncontrolled Phase I/II Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65

Study Start Date :

Sep 1, 2011

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rAAV2/4.hRPE65 3 cohortes of 3 patients each. All the patients enrolled in the study will receive a single subretinal injection in one eye. The eye, that will be injected, will be the eye with the poorest visual acuity.	Drug: rAAV2/4.hRPE65 One injection in on eye Cohorte 1 : 3 patients will receive one injection of up to 400 microliters of the IMP Cohorte 2 : 3 patients will receive one injection of up to 800 microliters of the IMP. Cohorte 3 : 3 patients under age of eighteen will receive one injection up to 400 or 800 microliters of the IMP.

Arm

Intervention/Treatment

Experimental: rAAV2/4.hRPE65

3 cohortes of 3 patients each. All the patients enrolled in the study will receive a single subretinal injection in one eye. The eye, that will be injected, will be the eye with the poorest visual acuity.

Drug: rAAV2/4.hRPE65

One injection in on eye Cohorte 1 : 3 patients will receive one injection of up to 400 microliters of the IMP Cohorte 2 : 3 patients will receive one injection of up to 800 microliters of the IMP. Cohorte 3 : 3 patients under age of eighteen will receive one injection up to 400 or 800 microliters of the IMP.

Outcome Measures

Primary Outcome Measures

The drug safety evaluation after administration [After administration of the gene therapy product.The patient will be folloed for the duration of the hospital stay, an average of 7 days]
Biodistribution : Urine sampling and nasal secretion will be collected at several time points after administration of the gene therapy product during all the duration of hospital stay, an average of 7 days.

Secondary Outcome Measures

Different efficacy parameters and immune parameters have to be measured to conclude on the overall amelioration of quality of life of enrolled patients [Between Day -120 and Day-7, Day 5, Day 14, Day 30 Day 60, Day 90, Day 120, Day 180, Day 360]
Recording global ERG (electroretinogram) Patient efficacy questionnaire Testing of far and near visual acuity, color vision, pupillometry, microperimetry and dark adaptation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Mutations that code for abnormal RPE65 protein
Presence of characteristic abnormalities in fundus
Dramatic reduction of both rods ans cones ERG responses
Low visual acuity <0.32
inform consent signed

Exclusion Criteria:

Patients with chronic conditions such a haematological, cardiac, renal diseases
Patients with, within the past 6 months, a clinically significant cardiac disease or known congestive heart failure, cardiac rhytm and conduction abnormalities
Patients with pulmonaty dysfunction
Patients with suspected rheumatoid arthritis
Patients with current systemic infection........

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU Nantes	Nantes		France	44000

Sponsors and Collaborators

Nantes University Hospital

Investigators

Principal Investigator: Michel WEBER, Professor, CHU Nantes

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Nantes University Hospital

ClinicalTrials.gov Identifier:

NCT01496040

Other Study ID Numbers:

BRD 07/08-K
2011-000418-21

First Posted:

Dec 21, 2011

Last Update Posted:

Oct 7, 2015

Last Verified:

Oct 1, 2015

Additional relevant MeSH terms:

Blindness

Retinal Dystrophies

Leber Congenital Amaurosis

Study Results

No Results Posted as of Oct 7, 2015