Administration of a genetically modified virus particle in patients with PDE6A-linked retinitis pigmentosa
- Conditions
- PDE6A-linked retinitis pigmentosaTherapeutic area: Diseases [C] - Eye Diseases [C11]
- Registration Number
- EUCTR2016-003705-34-DE
- Lead Sponsor
- niversitätsklinikum Tübingen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 9
• clinical diagnosis of retinitis pigmentosa
• confirmed mutation in PDE6A gene
• = 18 years of age
• visual acuity = 20/400
• no infection with Human Immundeficiency Virus (HIV)
• 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)
• 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.
• ability to understand and willingness to consent to study protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
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) yes
F.1.3.1 Number of subjects for this age range 9
Ocular (study eye & fellow eye)
• additional interfering ocular conditions with impact on study results (e.g. ocular opacity and advanced cataract, uveitis, amblyopia)
• recent (6 months) ocular surgery, intravitreal or subretinal implantation of a medical device
• disease causing mutations in another known retinitis pigmentosa gene
• ocular infection with herpes simplex virus in medical history
• history of ocular malignancies
• disorders of the internal retina (e.g. retinal detachment in the patients history)
• glaucoma defined as damage of the optic nerve
• vascular retinal occlusion
• diabetic patients suffering from retinopathy and/or macula edema
• any other retinopathy due to other diseases e.g. (but not limited to) arterial hypertension, trauma or acquired inflammatory diseases (uveitis serology), contraindication to pharmacological mydriasis (e.g. history of angle block glaucoma)
• absence of visual function on the contralateratel eye
Systemic
• systemic conditions (e.g. coronary heart disease, autoimmune disorders) which may affect study participation or outcome measures
• history of poorly controlled Diabetes Mellitus type 1 or type 2
• systemic illness or medically relevant abnormal laboratory values in blood analysis including renal and hepatic functions at inclusion
• patients treated with oral corticoids within 14 days prior inclusion
• current or recent participation in other study/or administration of biologic agent within the last three months
• known sensitivity to any compound used in the study
• contraindications to systemic immunosuppression
• contraindications in view of the planned surgery (e.g. but not limited to anaemia Hb<10g/dl, coagulopathy with PT/PTT >1,5 fold upper limit, hypertension with values above 180 mmHg systolic and 110 mmHg diastolic) including intolerance and contraindications to general anaesthesia
• intolerance to contrast agents used for diagnostic methods like angiography with fluoresceine or indocyanine green (e.g. but not limited to hyperthyroidism, hepatic insufficiency)
• subject/partner of childbearing potential unwilling to use adequate contraception for four months
• nursing or pregnant women
• any other cause that, in the investigator‘s opinion, renders potential subjects not suitable for the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary aim of the trial is to test the safety of subretinal delivery of rAAV.hPDE6A at different doses in patients with PDE6A-linked retinitis pigmentosa up to day 365 after treatment.;Secondary Objective: The investigation of treatment effects as reflected by patient reported outcomes and other standard clinical endpoints of visual function are secondary aims of the trial.;Primary end point(s): Safety as primary endpoint will be assessed by clinical examination of ocular inflammation (slit lamp, fundus biomicroscopy, and angiography) and laboratory analyses and will be assessed by ocular and non-ocular adverse events and their relationship to the study compound.;Timepoint(s) of evaluation of this end point: Timepoint of evaluation of primary endpoint is D365
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. BCVA assessed using the ETDRS visual acuity protocol<br>2. Contrast sensitivity (PR Charts)<br>3. Chromatic pupillography<br>4. FM-28<br>5. Scotopic visual field<br>6. Kinetic visual field<br>7. Multifocal-ERG<br>8. FAF, sdOCT and angiography recordings (ICG, FLA)<br>9. 6A-PRO (intervention-specific scale assessing patient reported outcome)<br>10. VFQ25;Timepoint(s) of evaluation of this end point: Assessments are performed at screening, D0, D1, D2, D14, D30, D90, D180, D365, M24, M36, M48, M60<br><br>For further details please refer to flowchart on page 17 of the protocol.