A phase I/II open label clinical trial, dose escalation study, involving a single injection under the retina of one eye of a mixture of two genetically modified viruses each containing one of the two halves of the human gene MYO7A, in subjects with Usher Syndrome type 1B retinitis pigmentosa.
- Conditions
- sher syndrome (USH) is characterized by the association of sensorineural hearing loss, Retinitis Pigmentosa (RP), and, in some cases, vestibular dysfunction. It is the most frequent cause of deaf-blindness. Retinal features in USH patients consist into a progressive photoreceptor degeneration, which leads to a loss of peripheral vision. This degeneration is predominantly attributable to rod dysfunction, although cones usually degenerate later in the course of the disease.MedDRA version: 20.0Level: PTClassification code 10063396Term: Usher's syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Eye Diseases [C11]
- Registration Number
- EUCTR2022-001092-14-IT
- Lead Sponsor
- FONDAZIONE TELETHO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 15
Part A:
1. Willingness to adhere to the protocol as evidenced by written informed consent.
2. Male and female adults diagnosed with USH1.
3. Molecular diagnosis of USH1B due to MYO7A mutations
(homozygotes or compound heterozygotes).
4. Age eighteen years old or older at the time of
administration.
5. 20/400 = Visual acuity = 20/80 and/or 5° < visual field <
20° in the eye to be injected.
6. Female subjects of childbearing potential have to use a
double method of contraception for 1 year after treatment. Male subjects who are partner of childbearing potential individual must use condom for 1 year after treatment.
Part B Cohort 1:
1. Willingness to adhere to the protocol as evidenced by written informed consent.
2. Male and female adults diagnosed with USH1.
3. Molecular diagnosis of USH1B due to MYO7A mutations
(homozygotes or compound heterozygotes).
4. Age eighteen years old or older at the time of
administration.
5. 20/200 = Visual acuity = 20/40 and/or 20° < visual field <
40° in the eye to be injected.
6. Female subjects of childbearing potential have to use a double method of contraception for the duration of 1 year. after treatment. Male subjects who are partner of childbearing potential individual must use a condom during intercourse for 1 year after treatment.
Part B Cohort 2:
1. Willingness to adhere to protocol as evidenced by written informed consent or parental informed consent and subject assent.
2. Male and female adults and children diagnosed with USH1.
3. Molecular diagnosis of USH1B due to MYO7A mutations
(homozygotes or compound heterozygotes).
4. Age eight years old or older at the time of administration.
5. 20/200 = Visual acuity = 20/40 and/or 20° < visual field <
40° in the eye to be injected.
6. Female subjects of childbearing potential have to use a double method of contraception for the duration of 1 year. after treatment. Male subjects who are partner of childbearing potential individual must use a condom during intercourse for 1 year after treatment.
Are the trial subjects under 18? yes
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 12
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Unable or unwilling to meet requirements of the study.
2. Unable to communicate with suitable verbal/auditory and/or
tactile sign language (in the opinion of the investigator).
3. Participation in a clinical study with an investigational drug in
the past six months.
4. Pre-existing eye conditions that would preclude the planned
surgery or interfere with the interpretation of study endpoints (for example, glaucoma, corneal or significant lenticular opacities, cystoid macular oedema, macular hole, uveitis).
5. Lack of sufficient viable retinal cells as determined by non- invasive means, such as OCT. Specifically, if indirect ophthalmoscopy reveals less than 1 disc area of retina which is not involved by complete retinal degeneration (indicated by geographic atrophy, thinning with tapetal sheen, or confluent intraretinal pigment migration), these eyes will be excluded. In addition, in eyes where OCT scans of sufficient quality can be obtained, areas of retina with thickness measurements less than 100 µm, or absence of neural retina, will not be targeted for delivery of dual AAV8 vector.
6. Complicating systemic diseases or clinically significant abnormal baseline laboratory values. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example, radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Also excluded would be subjects with immuno- compromising diseases, as there could be susceptibility to opportunistic infection (such as CMV retinitis). Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g. macular edema or proliferative changes). Subjects with juvenile rheumatoid arthritis could be excluded due to increased infection risk after surgery due to poor wound healing. Subjects who are positive for hepatitis B, C, and HIV will be excluded.
7. Prior ocular surgery within six months.
8. Known sensitivity to medications planned for use in the peri-
operative period.
9. Individuals who are pregnant or nursing
10. Any other condition that would not allow the potential subject
to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method