Long-Term Follow-Up Gene Therapy Study for Achromatopsia CNGB3 and CNGA3

Long-term Follow-up Study of Participants Following an Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/8-hCARp.hCNGB3 and AAV2/8-hG1.7p.coCNGA3) for Gene Therapy of Adults and Children With Achromatopsia Owing to Defects in CNGB3 or CNGA3

This is a longer-term follow-up study of patients with achromatopsia associated with defects in CNGA3 who participated in a clinical trial in which they received AAV-CNGA3 retinal gene therapy, or of patients with achromatopsia associated with defects in CNGB3 who participated in a clinical trial in which they received AAV-CNGB3 retinal gene therapy.

Study Overview

• Status: Terminated
• Conditions: Achromatopsia
• Intervention / Treatment: Biological: Prior exposure to AAV-CNGA3 or AAV-CNGB3

Detailed Description

The follow-up study is designed to collect data on the longer-term safety and efficacy of AAV-CNGA3 retinal gene therapy and AAV-CNGB3 retinal gene therapy.

• Study Type: Observational
• Enrollment (Actual): 34
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • 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 to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population are adults and children with achromatopsia resulting from mutations in CNGA3 or CNGB3.

Description

Inclusion in the study will be limited to individuals who:

1. Are able to give informed consent or assent, with or without the guidance of their parent(s)/guardian(s), where appropriate
2. Received AAV2/8-hCARp.hCNGB3 or AAV2/8-hG1.7p.coCNGA3 by intraocular administration in the prior open-label, Phase I/II, dose escalation study (EudraCT 2016-002290-35 or EudraCT 2018-003431-29)
3. Are willing to adhere to the protocol and long-term follow-up

Individuals will be excluded who:

Are unwilling or unable to meet the requirements of the study

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Low dose of AAV-CNGA3 or AAV-CNGB3; Subretinal administration of a single low dose of AAV-CNGA3 or AAV-CNGB3	Biological: Prior exposure to AAV-CNGA3 or AAV-CNGB3; Participants previously received AAV-CNGA3 or AAV-CNGB3 in an open-label, Phase 1/2 dose escalation trial for adults and children with achromatopsia owing to defects in CNGA3 or CNGB3, respectively.
Intermediate dose of AAV-CNGA3 or AAV-CNGB3; Subretinal administration of a single intermediate dose of AAV-CNGA3 or AAV-CNGB3	Biological: Prior exposure to AAV-CNGA3 or AAV-CNGB3; Participants previously received AAV-CNGA3 or AAV-CNGB3 in an open-label, Phase 1/2 dose escalation trial for adults and children with achromatopsia owing to defects in CNGA3 or CNGB3, respectively.
Other dose of AAV-CNGA3 or AAV-CNGB3; Subretinal administration of a single other dose (between the intermediate and high dose) of AAV-CNGA3 or AAV-CNGB3	Biological: Prior exposure to AAV-CNGA3 or AAV-CNGB3; Participants previously received AAV-CNGA3 or AAV-CNGB3 in an open-label, Phase 1/2 dose escalation trial for adults and children with achromatopsia owing to defects in CNGA3 or CNGB3, respectively.
High dose of AAV-CNGA3 or AAV-CNGB3; Subretinal administration of a single high dose of AAV-CNGA3 or AAV-CNGB3	Biological: Prior exposure to AAV-CNGA3 or AAV-CNGB3; Participants previously received AAV-CNGA3 or AAV-CNGB3 in an open-label, Phase 1/2 dose escalation trial for adults and children with achromatopsia owing to defects in CNGA3 or CNGB3, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events Related to the Treatment	The primary outcome measure is the longer-term safety of treatment with AAV-CNGA3 or AAV-CNGB3, assessed by the absence of IMP-related adverse events.	5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvements in Visual Function as Assessed by Visual Acuity at Month 12	Change from baseline to Month 12 in best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score in the treated eye. The direction of improvement from baseline is an increase in the number of ETDRS letters read over time.	12 months
Improvements in Visual Function as Assessed by Visual Acuity at Month 60	Change from baseline to Month 60 in best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score in the treated eye. The direction of improvement from baseline is an increase in the number of ETDRS letters read over time.	60 months
Improvements in Retinal Function as Assessed by Static Perimetry at Month 12	Change from baseline to Month 12 in contrast sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.	12 months
Improvements in Retinal Function as Assessed by Static Perimetry at Month 60	Change from baseline to Month 60 in contrast sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.	60 months
Quality of Life at Month 12 Measured by QoL Questionnaires in Children and Adolescents	Change from baseline to Month 12 in EuroQol-5D-Y 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 change from baseline reflects worsening.	12 months
Quality of Life at Month 60 Measured by QoL Questionnaires in Children and Adolescents	Change from baseline to Month 60 in EuroQol-5D-Y 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 change from baseline reflects worsening.	60 months
Quality of Life at Month 12 Measured by QoL Questionnaires in Adults	Change from baseline to Month 12 in EuroQol-5D-5L 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 change from baseline reflects worsening.	12 months
Quality of Life at Month 60 Measured by QoL Questionnaires in Adults	Change from baseline to Month 60 in EuroQol-5D-5L 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 change from baseline reflects worsening.	60 months

Collaborators and Investigators

• Sponsor: MeiraGTx UK II Ltd
• Collaborators: Syne Qua Non Limited; EMAS Pharma

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2017
• Primary Completion (Actual): April 4, 2024
• Study Completion (Actual): April 4, 2024

Study Registration Dates

• First Submitted: August 16, 2017
• First Submitted That Met QC Criteria: September 7, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Achromatopsia; CNGB3; CNGA3
• Additional Relevant MeSH Terms: Cone Dystrophy; Neurologic Manifestations; Nervous System Diseases; Eye Diseases; Eye Diseases, Hereditary; Vision Disorders; Sensation Disorders; Color Vision Defects
• Other Study ID Numbers: MGT007; 2016-003856-59 (EudraCT Number)

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