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.

A phase I/II open label, dose escalation study of sub-retinal administration of a “mixture of two adeno-associated viral vectors of serotype 8 containing the 5 ´- half sequence of the human MYO7A gene and the 3 ´- half sequence of the human MYO7A gene” in subjects with Usher syndrome type 1B (USH1B) retinitis pigmentosa. - TIGEM5_USH

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2022-001092-14-IT

Enrollment

Registered

2022-06-30

Start date

2023-10-12

Completion date

Unknown

Last updated

2024-12-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Usher 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: 20.0

Interventions

Product Name: PREDNISONE Product Code: [PREDNISONE] Pharmaceutical Form: Tablet INN or Proposed INN: PREDNISONE Current Sponsor code: PREDNISONE Concentration unit: mg/kg milligram(s)/kilogram Concent

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 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° =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 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.

Design outcomes

Primary

Measure	Time frame
Main Objective: Primary (Safety): 1) To assess the safety and tolerability of subretinal administration of the mixture of two adeno-associated viral vectors of serotype 8 containing the 5 ´- half sequence of the human MYO7A coding sequence and the 3 ´- half sequence of the human MYO7A coding sequence to deliver the full-lenght coding sequence for human MYO7A in subjects with USH1B retinitis pigmentosa 2) To determine the Maximum Tolerated Dose (MTD).;Secondary Objective: Secondary (Efficacy): To investigate the objective clinical ophthalmological measures of efficacy of subretinal administration of the mixture of two adeno-associated viral vectors of serotype 8 containing the 5 ´- half sequence of the human MYO7A coding sequence and the 3 ´- half sequence of the human MYO7A gene to deliver the full-lenght coding sequence for human MYO7A to subjects with USH1B retinitis pigmentosa.;Primary end point(s): 1) The incidence and severity of adverse events (AEs) including serious adverse events (SAEs). 2) The number and proportion of dose-limiting toxicities (DLTs) at each dose level.;Timepoint(s) of evaluation of this end point: The primary safety endpoints will be monitored in the days immediately following the administration of the drug and during the following the weeks, months and years, ie at visits: Visit 1 - Day 0 (day of injection); Visit 2 - Day 2; Visit 3 - Day 3; Visit 4 - Day 7; Visit 5 - Day 14; Visit 6 - Day 45; Visit 7 - Day 90; Visit 8 - Day 180; Visit 9 - Day 270; Visit 10 - 1 year after the injection; and in subsequent visits up to 3 years after the injection, as per the clinical protocol study design.	—

Measure

Time frame

Main Objective: Primary (Safety): 1) To assess the safety and tolerability of subretinal administration of the mixture of two adeno-associated viral vectors of serotype 8 containing the 5 ´- half sequence of the human MYO7A coding sequence and the 3 ´- half sequence of the human MYO7A coding sequence to deliver the full-lenght coding sequence for human MYO7A in subjects with USH1B retinitis pigmentosa 2) To determine the Maximum Tolerated Dose (MTD).;Secondary Objective: Secondary (Efficacy): To investigate the objective clinical ophthalmological measures of efficacy of subretinal administration of the mixture of two adeno-associated viral vectors of serotype 8 containing the 5 ´- half sequence of the human MYO7A coding sequence and the 3 ´- half sequence of the human MYO7A gene to deliver the full-lenght coding sequence for human MYO7A to subjects with USH1B retinitis pigmentosa.;Primary end point(s): 1) The incidence and severity of adverse events (AEs) including serious adverse events (SAEs). 2) The number and proportion of dose-limiting toxicities (DLTs) at each dose level.;Timepoint(s) of evaluation of this end point: The primary safety endpoints will be monitored in the days immediately following the administration of the drug and during the following the weeks, months and years, ie at visits: Visit 1 - Day 0 (day of injection); Visit 2 - Day 2; Visit 3 - Day 3; Visit 4 - Day 7; Visit 5 - Day 14; Visit 6 - Day 45; Visit 7 - Day 90; Visit 8 - Day 180; Visit 9 - Day 270; Visit 10 - 1 year after the injection; and in subsequent visits up to 3 years after the injection, as per the clinical protocol study design.

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Secondary

Measure	Time frame
Secondary end point(s): To assess the evolution in the retinal degeneration following subretinal injection of the Investigational Medicinal Product (IMP) in Part B of the study, the following clinical investigations will be conducted and evaluation at 6 months post IMP administration will be compared to baseline values as described below: • The main efficacy endpoint is an improvement in light sensitivity threshold measured with the full-field sensitivity threshold test. Other efficacy endpoints include: • Improvement in maximum constriction, as assessed by chromatic pupillometry test; • Enlargement of visual field, as assessed by semiautomic kinetic visual field; • Improvement of macular sensitivity, as assessed by microperimetry; • Finally, for patients older than 16 years, change in quality of life assessments will be evaluated.;Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints will be assessed prior to the administration of the IMP (at baseline) and post IMP injection at the following visits: Visit 6 - Day 45; Visit 8 - Day 180; Visit 10 - 1 year after the injection; Visit 12 - 2 years after the injection; Visit 14 - 3 years after injection, as per the clinical protocol study design.	—

Measure

Time frame

Secondary end point(s): To assess the evolution in the retinal degeneration following subretinal injection of the Investigational Medicinal Product (IMP) in Part B of the study, the following clinical investigations will be conducted and evaluation at 6 months post IMP administration will be compared to baseline values as described below: • The main efficacy endpoint is an improvement in light sensitivity threshold measured with the full-field sensitivity threshold test. Other efficacy endpoints include: • Improvement in maximum constriction, as assessed by chromatic pupillometry test; • Enlargement of visual field, as assessed by semiautomic kinetic visual field; • Improvement of macular sensitivity, as assessed by microperimetry; • Finally, for patients older than 16 years, change in quality of life assessments will be evaluated.;Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints will be assessed prior to the administration of the IMP (at baseline) and post IMP injection at the following visits: Visit 6 - Day 45; Visit 8 - Day 180; Visit 10 - 1 year after the injection; Visit 12 - 2 years after the injection; Visit 14 - 3 years after injection, as per the clinical protocol study design.

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Countries

Italy, Spain

Contacts

Public ContactSVILUPPO CLINICO

FONDAZIONE TELETHON ETS

szancan@telethon.it

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026