X-Linked Retinitis Pigmentosa caused by mutations in the RPGR gene MedDRA version: 20.0 Level: PT Classification code 10038914 Term: Retinitis pigmentosa System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: AAV2/5-hRKp.RPGR
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AAV2/5-hRKp.RPGR
Current Sponsor code: AAV2/5-hRKp.RPGR
Sponsors
MeiraGTx UK II Limited
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Inclusion in the trial will be limited to individuals who meet the following criteria: 1. Are males aged 5 years or older 2. Have X-linked retinitis pigmentosa confirmed by a retinal specialist (CI or PI) 3. Have relatively symmetrical retinal disease - both structurally and functionally defined as =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Individuals will be excluded if they meet any of the following criteria: 1. Have a known allergy to any of the non-investigational drugs to be used in the trial as defined in Section 5.4.1 2. Have participated in another research study involving an investigational medicinal therapy for ocular disease within the last 6 months 3. Have any other condition that the CI/PI considers makes them inappropriate for entry into the trial, inclusive of but not limited to a history of the following: o Uncontrolled hypertension defined as a systolic value =160mmHg or diastolic value =100mmHg. o Uncontrolled diabetes mellitus defined as an HbA1c =9% (75mmol/mol) at screening. o Uncontrolled heart failure (NYHA class II-IV). o Any history of tuberculosis o Chronic kidney disease (defined as eGFR =60ml/min calculated using Cockroft Gault or MDRD equations. o Immunocompromised state (including long term immunosuppressant therapy). o Osteoporosis (defined as presence of 1 or more non-traumatic “fragility” fractures or proven BMD of 2.5SD less than anticipated as demonstrated on DEXA scan). o Active peptic ulcer disease or uncontrolled gastro-oesophageal reflux. o Severe affective disorder or past history of drug induced psychosis 4. Use of high dose regular non-steroidal anti-inflammatory drugs at the time of screening. 5. Have an ocular or systemic disorder that may preclude subretinal surgery and/or interfere with interpretation of the study results 6. Have had intraocular surgery within 3 months of screening 7. Have recently (within 4 weeks of last dose of concomitant immunosuppressive therapy) received a live vaccine 8. Have a condition that requires glucocorticoid replacement therapy, such as in endocrine diseases, if this would interfere with the immunosuppressive regime. 9. Have known chronic hepatitis B infection as indicated by detectable surface antigen. Entry with negative surface antigens but positive hepatitis core antibody will be allowed however additional monitoring throughout the trial may be required. 10. 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 AAV2/5-hRKp.RPGR, for RGPR-ORF15 gene replacement in the retina of patients with RPGR XLRP. 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 and grade III or above non-ocular SUSAR. ;Secondary Objective: The secondary research objective is to determine whether AAV2/5-hRKp.RPGR for RGPR-ORF15 gene replacement in the retina can slow/halt progressive deterioration in retinal structure or visual function, and improve retinal function, visual function and quality of life in patients with RPGR XLRP.; Primary end point(s): The primary outcome is defined as absence of any of the below occurring during the 9 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, 12 weeks, 24 weeks, 9 months, 12 months, and 18 months after subretinal administration of the intervention. Safety will be assessed for 12 months after the intervention in this study, and a further 4 years in a separate follow on study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcomes are measures of the efficacy of the ATIMP; these will be performed on an individual participant basis and will be descriptive in nature. - Slowing or halting of progressive deterioration in retinal structure or visual function that is greater than the baseline variation for that test and is sustained for at least 2 consecutive assessments. Slowing or halting of progression over time may be facilitated by comparing identical structural and functional assessments acquired prior to intervention/injection to better determine rate of change over time in this slowly progressive disease #. #Historical images will be collected wherever possible with written informed consent from the participants - Any improvements in visual function from baseline that are greater than the baseline variation and are sustained for at least two consecutive assessments. - Any improvement in retinal function from pre-intervention that is greater than basleine 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, the low Luminance Questionnaire (LLQ) and the EQ5D-5L and EQ5D-5Y as appropriate. ;Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated at various time-points between 12 weeks and 18 months after subretinal administration of the intervention. | — |
Countries
United Kingdom, United States
Contacts
Public ContactOyinda Oluwole
MeiraGTx II UK Ltd
Outcome results
None listed