An Open-label Safety, Tolerability and Exploratory Efficacy Clinical Trial of PST-611 in Geographic Atrophy

Официальное название

An Open-label Multiple Dose Safety, Tolerability and Exploratory Efficacy Clinical Trial of PST-611 in Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration

Обзор

The goals of this interventional study are (1) to evaluate the safety and tolerability of multiple doses of PST-611 in men and women over the age of 65 with geographic atrophy secondary to age-related macular degeneration and (2) to assess efficacy of multiple doses of PST-611 by assessing retinal morphology and visual function changes over time. Participants will: * receive one dose every 20 weeks, for a total of 3 doses. * will be followed up for a total of 52 weeks following the first PST-611 dose.

Подробное описание

The maximum study duration per patient is 64 Weeks (including an up to 12 week screening/baseline period + 52 weeks of follow-up after the first dose). The study is a multiple dose study that investigates one PST-611 dose level for the 3 planned administrations. The study will enroll up to 24 participants.

Вмешательства

• Биопрепарат PST-611
  PST-611 is a naked plasmid DNA encoding human transferrin administered into the ciliary muscle

Первичные конечные точки

• Frequency and severity of ocular and non-ocular adverse events (Safety and Tolerability) [Срок оценки: Screening to week 52]

Вторичные конечные точки (9)

• Intraocular pressure [Срок оценки: Screening to week 52]
• Best corrected visual acuity [Срок оценки: Screening to week 52]
• Slit lamp biomicroscopy examination [Срок оценки: Screening to week 52]
• Dilated ophthalmoscopy examination [Срок оценки: Screening to week 52]
• Color fundus photography [Срок оценки: Screening to week 52]
• Spectral Domain-Optical Coherence Tomography [Срок оценки: Screening to week 52]
• Quantitative contrast sensitivity function [Срок оценки: screening to week 52]
• Area of retinal pigment epithelium (RPE) loss [Срок оценки: screening to week 52]
• Area of photoreceptor degeneration (EZ layer loss) [Срок оценки: Screening to week 52]

Критерии участия

Критерии включения

• Subjects must give written informed consent, be able to make the required trial visits and follow instructions.
• Female and male subjects must be 65 years of age or older.
• In the study eye (SE): cRORA must be present on OCT and attributed to AMD, as evaluated by the Investigator.
• Documented recent history (i.e., over 3 to 12 months prior to first PST-611 administration) of GA lesion area progression, with a yearly growth projection of ≥ 1.6 mm2, in the SE
• GA lesion area prior to the first PST-611 administration must be between 1.25 mm2 and 16 mm2, as assessed by OCT, in SE.
• BCVA must be < or = 75 ETDRS letters (Snellen < or = 20/32) in the SE.
• Fixation, either central or eccentric, of both eyes, must be compatible with the performance of the ocular imaging and functional assessments included in the trial, as evaluated by the Investigator.
• If both eyes are eligible, the SE will be selected by the Investigator based on the totality of the clinical evaluation.

Критерии исключения

• Both eyes (OU): any active intraocular or periocular infection or inflammation (eg, infectious blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis), or history of intraocular or periocular infection or inflammation in the 12 weeks (84 days) prior to Dose 1.
• SE: any intraocular surgery (including cataract surgery) or intravitreal (IVT) or periocular corticosteroid injection in the 12 weeks (84 days) prior to Dose 1.
• SE: the documented need for more than 2 anti-VEGF IVT treatments per year as well as any anti-VEGF IVT treatment within 3 months prior to Dose 1, and lesion must be clinically inactive.
• SE: media opacity that interferes with fundus imaging or is likely to require surgery during the trial period.
• SE: subject with history of glaucoma filtering surgery (e.g., trabeculectomy or aqueous shunt implant) or who underwent eye surgery in the 12 weeks (84 days) prior to Dose 1.
• SE: subject who has uncontrolled intraocular pressure of ≥ 25 mmHg in the SE at the Screening and Trial Baseline Visits.
• SE: subject with intraocular hypotension (<6 mmHg) in the SE that in the opinion of the Investigator would interfere with the PST-611 administrations or the evaluation of its safety or efficacy.
• SE: subject with history of scleritis, scleral thinning, cicatrizing conjunctival diseases, severe ocular allergies, severe ocular surface disease, ocular scarring or intraocular hardware (e.g., retained implant device) that could interfere with the PST-611 administrations or the evaluation of its safety.
• SE: any other concurrent ocular surface or intra-ocular condition, including retinal disease other than AMD, which, in the opinion of the Investigator, may pose a safety risk for the PST-611 administrations or interfere with the evaluation of its safety.
• Subject has any condition, which in the opinion of the Investigator, could compromise the subject's safety or adherence to the trial protocol or follow-up.
• Known/suspected hypersensitivity to any standard of care topical or local analgesics/anesthetics or other standard of care treatments used in the preparation of PST-611 administration procedure.
• Treatment with investigational medicinal products in the 12 weeks (84 days) prior to Dose 1.
• Subject previously exposed to any gene therapy product other than the non-viral gene therapy PST-611.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 3 центра

• CHU de Grenoble-Hôpital Michallon — Grenoble
• Hôpital Lariboisière — Paris
• Hôpital Cochin — Paris

Публикации

• Bigot K, Gondouin P, Benard R, Montagne P, Youale J, Piazza M, Picard E, Bordet T, Behar-Cohen F. Transferrin Non-Viral Gene Therapy for Treatment of Retinal Degeneration. Pharmaceutics. 2020 Sep 1;12(9):836. doi: 10.3390/pharmaceutics12090836. PMID 32882879

Идентификаторы

NCT: NCT07705568 · PST-611-CT2 · 2025-525008-12-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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