Gene Therapy for Achromatopsia (CNGA3) (CNGA3)

An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/8-hG1.7p.coCNGA3) for Gene Therapy of Children and Adults With Achromatopsia Owing to Defects in CNGA3

A clinical trial of adeno-associated virus vector (AAV) CNGA3 retinal gene therapy for patients with achromatopsia

Study Overview

• Status: Completed
• Conditions: Achromatopsia
• Intervention / Treatment: Biological: adeno-associated virus vector AAV- CNGA3

Detailed Description

CNGA3 retinal gene therapy for patients with achromatopsia

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital NHS Foundation Trust
• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Kellogg Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Are aged years or over
• Have achromatopsia confirmed by a retinal specialist investigator

Exclusion Criteria:

• Are females who are pregnant or breastfeeding
• Have participated in another research study involving an investigational medicinal therapy for ocular disease within the last 6 months
• Have any other condition that the investigator considers makes them inappropriate for entry into the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose adeno-associated virus (AAV) CNGA3; Subretinal administration of a single low dose AAV CNGA3	Biological: adeno-associated virus vector AAV- CNGA3; Adeno-associated virus (AAV) gene therapy for defects in CNGA3 gene
Experimental: Intermediate dose adeno-associated virus (AAV) CNGA3; Subretinal administration of a single intermediate dose AAV CNGA3	Biological: adeno-associated virus vector AAV- CNGA3; Adeno-associated virus (AAV) gene therapy for defects in CNGA3 gene
Experimental: High dose adeno-associated virus (AAV) CNGA3; Subretinal administration of a single high dose AAV CNGA3	Biological: adeno-associated virus vector AAV- CNGA3; Adeno-associated virus (AAV) gene therapy for defects in CNGA3 gene

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Meeting the Primary Outcome Defined as Any of the Below Events Occurring During the 6 Weeks Following Administration, at Least Possibly Related to the Advanced Therapy Investigational Medicinal Products (ATIMP), Not Surgery Alone.	The primary outcome is defined as any of the below occurring during the 6 weeks following administration, at least possibly related to the Advanced Therapy Investigational Medicinal Products (ATIMP), not surgery alone: Reduction in visual acuity by 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more that fails to resolve to within 15 letters of baseline in a 4-week period once prophylactic treatment commences; Severe unresponsive inflammation; Infective endophthalmitis; Ocular malignancy; Grade III or above non-ocular Suspected Unexpected Serious Adverse Reaction (SUSAR)	6 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvements in Visual Function as Assessed by Visual Acuity	Change from baseline to Week 24 in best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score. The direction of improvement from baseline is an increase in the number of ETDRS letters read over time.	6 Months
Improvements in Retinal Function as Assessed by Static Perimetry	Change from baseline to Week 24 in mean retinal sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.	6 Months
Quality of Life Measured by QoL Questionnaires in Children and Adolescents	Change from baseline to Week 24 in EuroQol Visual Analogue Scale (EQ-VAS) in children and adolescents. EQ-VAS uses a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A positive change from baseline reflects improvement and a negative reflects worsening.	6 Months
Quality of Life Measured by QoL Questionnaires in Adults	Change from baseline to Week 24 in EuroQol Visual Analogue Scale (EQ-VAS) in adults. EQ-VAS uses a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A positive change from baseline reflects improvement and a negative reflects worsening.	6 Months

Collaborators and Investigators

• Sponsor: MeiraGTx UK II Ltd
• Collaborators: Janssen Research & Development, LLC
• Investigators: Principal Investigator: James Bainbridge, Chief Investigator

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Actual): June 10, 2021
• Study Completion (Actual): June 10, 2021

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Actual): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Eye Diseases, Hereditary; Sensation Disorders; Vision Disorders; Cone Dystrophy; Color Vision Defects
• Other Study ID Numbers: MGT012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No