Leber Congenital Amaurosis (LCA) caused by mutations in RPE65 MedDRA version: 20.0 Level: PT Classification code 10070667 Term: Leber's congenital amaurosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: AAV2/5-OPTIRPE65
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AAV2/5-OPTIRPE65
Current Sponsor code: AAV2/5-OPTIRPE65
Concentration unit: billion organisms/ml billion
Sponsors
MeiraGTx UK II Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion in the trial will be limited to individuals who: • Are aged 3 years or older • Have early-onset severe retinal dystrophy consistent with RPE65 deficiency • Have homozygous or compound heterozygous missense or null mutations in RPE65 confirmed in accredited laboratory • Have functional or structural evidence of photoreceptor preservation as assessed by static perimetry (for visual field assessment) and SD-OCT scanning respectively • Are able to give informed consent or assent, with the guidance of their parent/guardian where appropriate • Are able to undertake age-appropriate clinical assessments • If female and of child bearing potential, are willing to use an effective form of birth control (hormonal or barrier method of birth control; or abstinence) for at least 12 months following ATIMP administration • If male, are willing to use barrier and spermicide form of contraceptive or maintain sexual abstinence for at least 12 months following ATIMP administration • Females of childbearing potential will have a negative pregnancy test on the day of ATIMP administration. Participants are considered not of childbearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy or bilateral oophorectomy) or post-menopausal • Are willing to give consent for the use of blood and blood components collected throughout the trial for the investigation of immune responses to the 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 9 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Individuals will be excluded who: • Are females who are pregnant or breastfeeding • Have contraindications for transient immune-suppression by systemic corticosteroids (including uncontrolled hypertension, diabetes mellitus, tuberculosis, renal impairment, osteoporosis, gastric ulceration, severe affective disorder) or are immunocompromised • Have a previous history (within 5 years) of gastric or duodenal ulceration, hiatus hernia, uncontrolled gastro-oesphageal reflux or are using non-steroidal anti-inflammatory drugs on a regular basis at the time of screening • Have a known allergy to any of the non-investigational drugs to be used in the trial • 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 PI considers makes them inappropriate for entry into the trial • Have had intraocular 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 • Are unwilling to consider the possibility of entry into a subsequent longer term follow up study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary research objective is to assess the safety of a new optimised virus vector for RPE gene replacement in the retina. Safety is defined as an ATIMP related: - Reduction in visual acuity by 15 ETDRS letters or more - Severe unresponsive inflammation (defined below) - Infective endophthalmitis - Ocular malignancy - Grade III or above non-ocular SUSAR Classification of severe unresponsive inflammation will be according to the SUN (standardisation of uveitis nomenclature) Working Group grading system (Am J Ophthalmol. 2005 Sep;140(3):50916.) i.e. - anterior chamber cells 3+ (26-50 cells in a field size of 1mm x 1-mm slit-beam), or - anterior chamber flare 3+ (marked, iris and lens details hazy) or - vitreous haze 3+ (Ophthalmology 1985; 92:467-71) that fail to improve by 2 steps (or to grade 0) during a 6 week period.;Secondary Objective: The secondary research objective is to determine whether the new AAV2/5-OPTIRPE65 is effective at improving sight in terms of both visual and retinal function, and quality of life.;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, 9 weeks, 3 months, and 6 months after subretinal administration of the intervention. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcomes are measures of the efficacy of the intervention; these will be performed on an individual participant basis and will be descriptive in nature. Efficacy will be defined as: - Any improvement in visual function from baseline that is greater that the test-retest variation for that test and is sustained for at least two consecutive assessments. - Any improvement in retinal function from pre-intervention that is greater than the test-retest variation and measurable by electroretinography (ERG). - If no ERG is previously detectable, then the presence of any reproducible response with appropriate waveform would be significant. If an ERG is there to start with, any of the following would be significant: an improvement in amplitude of >50 % in DA 0.01 b-wave (rod system sensitivity); bright flash DA 10 a- wave (photoreceptor improvement); the 30Hz flicker; and the LA 3.0 photopic a- and b-waves. In terms of timing: > 3ms improvement in photopic parameters and bright flash DA 10 a-wave; 3-6ms for the DA 0.01 and DA 10.0 b-waves. Quality of life will be measured by the Impact of Visual Impairment (IVI) questionnaire and the EQ5D-5Land EQ-5D-Y. 2.3) Quality of life will be measured by the Impact of Visual Impairment (IVI) questionnaire and the EQ5D-5L and with vision bolt on. ;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 ContactJulie Bakobaki
MeiraGTx UK II Ltd
Outcome results
None listed