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About
The purpose of this study is to proof the safety and efficacy of a single bilateral subretinal injection of rAAV.hCNGA3 in adult and minor patients with CNGA3-linked achromatopsia.
Full description
Title: Safety and efficacy of a bilateral single subretinal injection of rAAV.hCNGA3 in adult and minor patients with CNGA3-linked achromatopsia investigated in a randomized, wait list controlled, observer-masked trial
Phase: I/II
Indication: CNGA3-linked achromatopsia
Aim: to proof the safety and efficacy of a single bilateral subretinal injection of rAAV.hCNGA3 in adult and minor patients with CNGA3-linked achromatopsia.
Study design: open, mono-center, randomized, wait list controlled, observer-masked trial
Study Population:
Inclusion Criteria (Both Eyes)
Exclusion Criteria
Patient Number: 3 Strata: Cohort A n = 4, ≥ 18 years of age and previous participation in phaseI/II, Cohort B n = 4, ≥ 18 years of age, Cohort C n= 6, 6-12 years of age
Treatment:
Each cohort will receive a single subretinal injection of 1x10e11 vector genome particles of rAAV.hCNGA3 in each eye at different time-points. Cohort A, in whom the first eye has received treatment under protocol version 5.0, will only receive one injection in the second eye.
After standard three-port 23G pars plana vitrectomy, balanced salt solution will be used to induce a localized primary retinal detachment in a controlled fashion. Vector solution will be applied using disposable 41G extendible subretinal injection needles within a standard 23G body to fit the port system.
Primary Endpoint:
Primary endpoint safety: Safety assessment 12 months after treatment, descriptively Primary endpoint efficacy: Contrast sensitivity (Pelli Robson 3 m) 6 months after treatment
Key secondary endpoints efficacy 12 months after treatment:
Statistical Methods:
Efficacy: The analysis of the primary endpoint (contrast sensitivity after 6 months) will be done using a pre / post comparison for the entire sample including both eyes for cohort B and C (n=10) and only one eye for cohort A (n=4) with GEE correction for the dependency of left and right eye. In the waiting group the second (therapeutic) phase will be used. The dependency appears for cohorts B and C which contribute both eyes but not for cohort A which contributes only one eye to the efficacy analysis. The study is powered for this analysis. We will use the specific type of IEE (Independence Estimating Equations) which reveals correct standard errors and a robust estimate for model parameters.
Additionally, we will compare the Intervention group vs. control group (waiting group) (n=7 vs. 7), using baseline adjusted analysis of covariance and between subject comparisons. This analysis will use GEEs as described for the primary analysis including both eyes of cohort B and C and only the newly treated eye in cohort A. This analysis will be descriptive and provide evidence for the planning of a randomized Phase III trial.
The primary analysis population will be the ITT in which only patients with baseline measurements will be included. For patients providing baseline measurements in one eye, only this eye will be included. Multiple imputation will be done with sampling unit "eye" if only baseline, but not follow up data are available. Descriptive parameters will be given for the full cohort (n=14) and for the sub-strata (n=4, 4, 6 pooled), additionally, correlation analysis descriptively for the comparison of subjective and objective measurements will be done.
Safety (ITT): AEs and SAEs will be documented using line listings and tabulations (MedDRA code will be applied). Frequency tabulations of certain classes of events will be given including two-sided 95% confidence intervals.
The aim of analysis (1) is to gain evidence for a sample size estimation for a phase III trial with similar design, where analysis (2) will be confirmatory and powered according to a sample size estimation.
Time Schedule: of trial November 2015 end of recruitment 04/2022, end of trial 04/2027, duration of trial per patient: one year with four years of follow-up.
The final study report will be prepared after completion of the four year follow-up period (5 years after treatment).
Enrollment
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Inclusion and exclusion criteria
Inclusion Criteria (Both Eyes)
Exclusion Criteria
Primary purpose
Allocation
Interventional model
Masking
13 participants in 2 patient groups
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Central trial contact
Barbara J Wilhelm, Prof.; Dominik Fischer, Prof.
Data sourced from clinicaltrials.gov
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