Achromatopsia caused by mutations in the CNGB3 gene MedDRA version: 20.0 Level: LLT Classification code 10000454 Term: Achromatopsia System Organ Class: 100000004850
Conditions
Interventions
Product Name: AAV2/8-hCARp.hCNGB3
Pharmaceutical Form: Solution for injection
Concentration unit: billion organisms/ml billion organisms/millilitre
Conc
Sponsors
MeiraGTx UK II Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion in the trial will be limited to individuals who: • Are aged 3 years or older (children will be included only once the maximal tolerated dose has been determined) • Have Achromatopsia caused by mutations in CNGB3 • Present evidence of preservation of photoreceptors at the macula • Are able to undertake age-appropriate clinical assessments • Are willing to give consent for the use of blood and blood components collected throughout the trial for the investigation of immune response to ATIMP Are the trial subjects under 18? yes Number of subjects for this age range: 9 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Individuals will be excluded who: • Are females who are pregnant or breastfeeding • Had intra-ocular surgery within 6 months of screening • Have an ocular or systemic disorder that may preclude subretinal surgery and/or interfere with interpretation of the study results. • Have participated in another research study involving an investigational therapy for ocular disease within the last 6 months • Have any other condition that the PI considers makes them inappropriate for entry into the trial, inclusive of but not limited to a history of the following: hypertension, diabetes mellitus, tuberculosis, renal impairment, immunocompromised state, osteoporosis, gastric ulceration or severe affective disorder • Are unwilling to consider the possibility of entry into a subsequent longer term follow up study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary research objective is to determine whether a AAV2/8 vector for hCNGB3 gene replacement in the retina can improve retinal function, visual function and quality of life.; Main Objective: The primary research objective is to assess the safety of a AAV2/8 vector for hCNGB3 gene replacement in the retina. Safety is defined as the absence of an ATIMP-related: • Reduction in visual acuity by 15 ETDRS letters or more • Severe unresponsive inflammation • Infective endophthalmitis • Ocular malignancy • Grade III or above non-ocular SUSAR ; Primary end point(s): The primary outcome is defined as any of the below occurring during the 6 weeks following administration, at least possibly related to the ATIMP, not surgery alone: • Reduction in visual acuity by 15 ETDRS letters or more • Severe unresponsive inflammation • Infective endophthalmitis • Ocular malignancy • Grade III or above non-ocular SUSAR ; Timepoint(s) of evaluation of this end point: This endpoint will be evaluated at 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, 12 weeks, and 24 weeks after subretinal administration of the intervention. Safety will be assessed for a further 4.5 years in a separate subsequent study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcomes are measures of the efficacy of the intervention, which will be performed on an individual participant basis and will be descriptive in nature. • Any improvements in visual function from baseline that are greater than the test-retest variation and are sustained for at least two consecutive assessments. • Any improvement in retinal function from pre-intervention that is greater than test-retest variation and measurable by electrophysiology (pattern ERG, multifocal ERG or full-field ERG). • Quality of life will be measured by the Impact of Visual Impairment (IVI) questionnaire and the EQ5D-5L and EQ5D-Y ;Timepoint(s) of evaluation of this end point: This endpoint will be evaluated at 3 months and 6 months after subretinal administration of the intervention. | — |
Countries
United Kingdom, United States
Contacts
Public ContactAmy De Sa
MeiraGTx II UK Ltd
Outcome results
None listed