Gene Therapy for Achromatopsia (CNGB3)

Study Overview
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Brief Summary
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A clinical trial of AAV - CNGB3 retinal gene therapy for patients with achromatopsia

Detailed Description
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CNGB3 retinal gene therapy for patients with achromatopsia

Official Title
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An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/8-hCARp.hCNGB3) for Gene Therapy of Adults and Children With Achromatopsia Owing to Defects in CNGB3

Conditions
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Achromatopsia

Intervention / Treatment
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* Biological: AAV - CNGB3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are aged 3 years or older Have achromatopsia confirmed by a retinal specialist (CI or PI) 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 CI/PI considers makes them inappropriate for entry into the trial

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biological-Low dose AAV - CNGB3<br>Subretinal administration of a single low dose of AAV - CNGB3 | Biological: AAV - CNGB3<br>* Comparison of different dosages of AAV-CNGB3<br>|
| Experimental: Biological-Medium dose AAV - CNGB3<br>Subretinal administration of a single intermediate dose of AAV - CNGB3 | Biological: AAV - CNGB3<br>* Comparison of different dosages of AAV-CNGB3<br>|
| Experimental: Biological-High dose AAV - CNGB3<br>Subretinal administration of a single high dose of AAV - CNGB3 | Biological: AAV - CNGB3<br>* Comparison of different dosages of AAV-CNGB3<br>|

What is the study measuring?
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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 in the treated eye. 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-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. | 6 months | 
| Quality of Life Measured by QoL Questionnaires in Adults | Change from baseline to Week 24 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. | 6 Months |