Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm With Untreated Patients

Официальное название

An Open Label, Dose Exploration, Safety and Tolerability Study of a Subretinal Injection of an OPGx-001 Gene Vector to Participants With LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) With OCncurrent Non-Interventional Follow-Up of Untreated Patients

Обзор

The goals of this clinical trial are assess the natural course of LCA5-IRD over 6 months and to evaluate the safety and preliminary efficacy of subretinal gene therapy with OPGx-001 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene. Funding Source- FDA Office of Orphan Products Development (OOPD).

Подробное описание

This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating untreated patients for 6 months and with three doses of OPGx-001 for the treatment of LCA5-IRD.

Enrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC).

Concurrently, 16 untreated patients will be assessed for 6 months prior to treatment to study the natural course of LCA5-IRD.

Вмешательства

• Биопрепарат AAV8.hLCA5
  Adeno-associated virus vector expressing human LCA5 gene

Первичные конечные точки

• Incidence of Dose Limiting Toxicities [Срок оценки: 2 years]
• Number of adverse events related to OPGx-001 [Срок оценки: 2 years]
• Incidence of adverse events related to OPGx-001 [Срок оценки: 2 years]
• Severity of adverse events related to OPGx-001 [Срок оценки: 2 years]
• Number of procedure-related adverse events [Срок оценки: 2 years]
• Incidence of procedure-related adverse events [Срок оценки: 2 years]
• Severity of procedure-related adverse events [Срок оценки: 2 years]
• Assessment of cross-sectional spectral domain optical coherence tomography images [Срок оценки: 2 years]
• Assessment of Natural course of LCA5-IRD [Срок оценки: 6 months]
• Assessment of Natural course of LCA5-IRD [Срок оценки: 6 months]

Вторичные конечные точки (4)

• Change from baseline over time in Multi-luminance Orientation and Mobility Test [Срок оценки: 2 years]
• Change from baseline over time in Dark-adapted full-field sensitivity testing [Срок оценки: 2 years]
• Change from baseline over time in best corrected visual acuity (BCVA) [Срок оценки: 2 years]
• Change from baseline over time in visual functioning questionnaire [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Are willing and able to provide written informed consent (ICF) and, where appropriate, willing to sign an assent prior to any study procedures.
• Are willing to adhere to the clinical protocol and able to perform testing procedures.
• In part A participants must be 13 years of age or older at consent, for Part B, participants must be 4 years of age or older at consent with the ability to conduct the MLoMT.
• Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (historic testing up to 15 years from date of consent can be considered).
• Visual acuity: BCVA < 20/80 on the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart (modified for low vision participants) in the eye to be treated
• Show evidence of detectable photoreceptors by Spectral Domain Optical Coherence Tomography (SD-OCT)
• Participant is a good candidate for surgery per investigator judgement
• Participant agrees to follow direction of investigator regarding restrictions post-surgery (Part A only).

Критерии исключения

• Women who are pregnant or individuals (women of childbearing potential and men) unwilling to use effective contraception for the duration of the study, including barrier methods for the first year after investigational product (IP) administration (Part A only).
• Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery. This includes individuals who are immunocompromised.
• History of intraocular surgery for either eye within 6 months prior to planned IP administration (Part A only).
• Have previously received gene therapy.
• Have used any investigational drug or device within 90 days or 5 estimated half-lives of treatment, whichever is longer or plan to participate in another study of drug or device during the study period.
• History of disease which may preclude the participant from participation, or which may interfere with outcome measure testing or test results.
• Incapable of performing visual function testing (e.g., FST testing) for reasons other than poor vision.
• Any absolute contraindication to a course of oral steroids.
• Any other condition that would not allow the potential participant to complete follow-up examinations during the study and, in the opinion of the Investigator, makes the potential participant unsuitable for the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 2 центра

• University of Pennsylvania Perelman School of Medicine — Philadelphia
• Retina Foundation of the Southwest — Dallas

Идентификаторы

NCT: NCT05616793 · OPGx-LCA5-1001 · FD-R-008174

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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