CNGA3-linked achromatopsia MedDRA version: 20.0 Level: LLT Classification code 10000454 Term: Achromatopsia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: rAAV.hCNGA3 vector
Product Code: ACHM2
Pharmaceutical Form: Concentrate for solution for injection
Sponsors
Universitätsklinikum Tübingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • clinical diagnosis of achromatopsia • 6-12 years of age • = 18 years of age • bi-allelic pathogenic or likely pathogenic mutations in CNGA3 • BCVA = 20/400 • a minimal outer nuclear layer thickness of 10µm at 3° eccentricity (normal = 38±6µm) • ability to understand and willingness to consent to study protocol • no infection with Human Immundeficiency Virus (HIV) • Male patients must agree to use condoms during the first 6 months post treatment. • Female patients of childbearing potential must agree to use an effective method of birth control during the first 6 months post treatment. • negative pregnancy test in women with childbearing potential (a woman who is two years post-menopausal or surgically sterile is not considered to be of childbearing potential) Are the trial subjects under 18? yes Number of subjects for this age range: 6 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • any other retinopathy due to other diseases e.g. (but not limited to) arterial hypertension, trauma or acquired inflammatory diseases (uveitis serology) , retinopathy of the premature • systemic conditions (e.g. coronary heart disease, congenital/genetic conditions, autoimmune disorders) which may affect study participation or outcome measures • current or recent participation in other study or administration of biologic agent within the last three months • recent (within the last 6 months) ocular surgery, intravitreal or subretinal implantation of a medical device • known sensitivity to any compound used in the study • contraindications to systemic immunosuppression • subject/partner of childbearing potential unwilling to use adequate contraception for six months after dosing • nursing or pregnant female subject • any other cause that, in the investigator‘s opinion, renders potential subjects not suitable for the study • causal mutations in other genes for hereditary retinal diseases • contraindications in view of the planned surgery (e.g. anaemia Hb 7%) Diabetes Mellitus type 1 or type 2 • patients treated with systemic corticoids within 14 days prior inclusion • systemic illness or medically significant abnormal laboratory values >3 UNL in blood analysis including renal and hepatic functions at inclusion • absence of vision on the contralateral eye • contraindication to pharmacological mydriasis (e.g. history of angle block glaucoma)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objective: The primary aim of the trial is the investigation of the safety of rAAV.hCNGA3 after bilateral subretinal injection in adult and minor patients with CNGA3-linked achromatopsia. ;Secondary Objective: The investigation of treatment effects as reflected by patient/parent reported outcomes and the efficacy of the intervention on visual functions are secondary aims of the trial. ;Primary end point(s): E.5.1Primary End Point (repeat as necessary) : Primary Endpoint safety: •Incidence and severity of ocular adverse events •Incidence and severity of non-ocular adverse events Safety will be assessed by clinical examination of ocular inflammation (slit lamp, fundus biomicroscopy), fundus photography, fundus autofluorescence and by evaluation of rod function in the treated area (DAC and scotopic CPC). Systemic safety will be assessed by vital signs, routine clinical chemistry testing (including CRP, ESR) and full/differential blood counts. Immunopathology essays will include specific enzyme-linked immunosorbent assays for humoral antibodies against rAAV8 capsid protein. Adverse events of special interest (AESI) -Adverse immunological reaction both systemic and ocular, defined by e.g. - but not limited to - blood parameters, findings in slit lamp examination. -Severe vision loss, defined by more than 15 ETDRS letters loss compared to screening more than 56 days after surgery. SAEs and AESIs must be reported to the sponsor within 24h, the sponsor is obliged to inform the DMC immediately. The procedure is defined on the SAE worksheet. ;Timepoint(s) of evaluation of this end point: Primary endpoint safety: Safety assessment 12 months after treatment (incidence and severity of ocular and non-ocular adverse events) Primary endpoint efficacy: Contrast sensitivity (Pelli Robson 3 m) 6 months after treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints efficacy: • Contrast sensitivity (Pelli Robson 3 m) • BCVA assessed using the ETDRS visual acuity protocol • FrACT (Freiburg Visual Acuity & Contrast Test) • Roth FM28 sat • VA-CAL (Visual acuity under different conditions of contrast and ambient light) • Patient reported outcomes (VFQ25/CVFQ, A3-PRO) • Electroretinography • Chromatic pupil campimetry (CPC) cone protocol – exploratory - functional Secondary endpoints safety: • Changes in various outcome measures, as determined by • Spectral domain optical coherence tomography (SD-OCT) morphological • Chromatic pupil campimetry (CPC) rod protocol – exploratory - functional • Dark-adapted chromatic perimetry (DAC) – exploratory - functional ;Timepoint(s) of evaluation of this end point: Timepoint(s) of evaluation of this endpoint: 12 months after treatment | — |
Countries
Germany
Contacts
Public ContactHead of STZ eyetrial, Dr. T. Peters
STZ eyetrial am Department für Augenheilkunde
Outcome results
None listed