Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-related Macular Degeneration (AQUARIUS)

Официальное название

A Multi-center, Randomized, Double-masked, Active-comparator-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-related Macular Degeneration (AQUARIUS)

Обзор

This is a multi-center, randomized, double-masked, active-comparator-controlled, Phase 3 study in a broad participant population (treatment-naïve and treatment-experienced) with neovascular (wet) age-related macular degeneration (nAMD). The study will evaluate a single intravitreal (IVT) injection of Ixo-vec compared to intravitreal aflibercept (active comparator). The primary endpoint of this study is the mean change in best corrected visual acuity (BCVA) of Ixo-vec compared to an active comparator measured as an average at Weeks 52 and 56. Safety, tolerability, and efficacy will be evaluated throughout the study.

Подробное описание

The primary objective of this study is to evaluate the non-inferiority in efficacy of a single IVT injection of Ixo-vec 6 x 10\^10 vector genome (vg)/eye compared to an active comparator. Non-inferiority will be evaluated using a pre-specified margin defined in the protocol.

Neovascular AMD is a degenerative ocular disease associated with the infiltration of abnormal blood vessels in the retina from the underlying choroid layer and is a leading cause of blindness in patients over 65 years of age. The abnormal angiogenic process in nAMD is stimulated and modulated by vascular endothelial growth factor (VEGF). Treatment of nAMD requires frequent IVT injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. Ixo-vec (also known as ADVM-022 or AAV.7m8-aflibercept) is an adeno-associated virus (AAV)-based gene therapy product being developed for the treatment of nAMD. Ixo-vec is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with nAMD receiving anti-VEGF therapy in clinical practice.

Safety, tolerability, and efficacy will be evaluated throughout this study. The primary endpoint of this study is the mean change in BCVA of Ixo-vec compared to an active comparator measured as an average at Weeks 52 and 56 post-treatment.

Due to the long duration of the Screening period, this study will be considered fully enrolled when randomization has been completed.

Вмешательства

• Генная терапия Ixo-vec
  Ixo-vec will be administered intravitreally.
• Препарат Aflibercept
  Aflibercept will be administered intravitreally.

Первичные конечные точки

• Mean Change from Baseline in BCVA Based on an Average at Weeks 52 and 56 [Срок оценки: Baseline, Week 52 and Week 56]

Вторичные конечные точки (12)

• Mean Number of Aflibercept IVT Injections Received [Срок оценки: Week 4 through Week 56]
• Percentage of Participants with Worsened BCVA [Срок оценки: Through Week 56]
• Percentage of Participants with Improved BCVA [Срок оценки: Through Week 56]
• Mean Change from Baseline in BCVA Over Time Based on an Average at Weeks 52 and 56 [Срок оценки: Baseline Through Week 56]
• Mean Change from Week 1 in BCVA Based on an Average at Weeks 52 and 56 [Срок оценки: Week 1 through Week 56]
• Percentage of Participants with BCVA of 73 Letters or More from Week 4 Through Week 56 [Срок оценки: Week 4 through Week 56]
• Mean Change in Central Subfield Thickness (CST) from Baseline Over Time Through Week 56 [Срок оценки: Baseline Through Week 56]
• Percentage of Participants with CST ≤ 300 μm Over Time Through Week 56 [Срок оценки: Through Week 56]
• Mean Number of CST Fluctuations > 50 μm From Week 1 Over Time Through Week 56 [Срок оценки: Week 1 through Week 56]
• Percentage of Participants with CST Fluctuations > 50 μm from Week 1 Over Time Through Week 56 [Срок оценки: Week 1 through Week 56]
• Percent Reduction in Mean Rate of Annualized Anti-VEGF Injections [Срок оценки: Through Week 56]
• Percentage of Participants Who Were Aflibercept Injection-free [Срок оценки: Week 4 through Week 56]

Критерии участия

Критерии включения

• Able and willing to provide informed consent (or have a legally authorized representative who is able and willing to provide informed consent) prior to any study assessments and procedures and comply with the study requirements and visits.
• Male or female with a diagnosis of CNV secondary to nAMD in the study eye, with nAMD disease activity at Screening Visit 1.
• At least 50 years old at Screening Visit 1.
• An ETDRS BCVA letter score of 35 - 78 (approximate Snellen equivalent of 20/200 to 20/32) in the study eye at Screening Visit 1.
• Demonstrated a meaningful anatomic response to anti-VEGF therapy during screening.
• Able to reliably use eye drops per protocol.

Критерии исключения

General Exclusion Criteria

• History of a medical condition giving reasonable suspicion of a condition that contraindicates the use of Ixo-vec, compromises the participant's ability to comply with the planned study activities, or that might affect the interpretation of the results of the study or render the participant at high risk for treatment complications in the opinion of the Investigator. History of severe coronavirus disease (COVID-19) infection may meet this exclusion criterion if, in the opinion of the Investigator, it is likely to lead to any important complications.
• Received any prior gene therapy.
• Prior treatment with any non-gene therapy investigational medicinal product (IMP) or medical device in the study eye within 3 months of Screening Visit 1 or 5 half-lives of the IMP prior to dosing with Ixo-vec, whichever is longer.
• Female participants who are pregnant or breastfeeding or who intend to become pregnant or breastfeed in the future.
• History or evidence of any of the following cardiovascular diseases:

• Myocardial infarction in the 6-month period prior to Week 1.
• Uncontrolled hypertension defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg during screening.
• Stroke in the 6-month period prior to Week 1.
• History of ongoing bleeding disorders. The use of aspirin or other anticoagulants (e.g., Factor Xa inhibitors) is permitted.
• Use of systemic immunosuppressive drugs within 90 days prior to Screening Visit 1. Short courses of oral corticosteroids are permitted, as well as any inhaled, intra-articular, nasal or dermal steroid use.
• Evidence of poorly controlled diabetes or glycated hemoglobin (HbA1c) ≥ 8.0% during screening.

Ocular Exclusion Criteria

• Any active ocular or periocular infection in the study eye from Screening Visit 1.
• History or evidence of the following in the study eye:

• Intraocular or refractive surgery within 5 months prior to Week 1.
• Any previous penetrating keratoplasty or vitrectomy.
• Any previous panretinal photocoagulation.
• Any previous submacular surgery, other surgical intervention (including port delivery system) or laser treatment for age-related macular degeneration.
• Any history or evidence of retinal detachment (with or without repair) or retinal pigment epithelium rip/tear in the study eye, as determined by the Investigator during screening or at Week 1.
• Uncontrolled ocular hypertension or glaucoma in the study eye from Screening Visit 1 to Week 1 or current use of ≥ 2 intraocular pressure (IOP) lowering medications or normal tension glaucoma/suspect in the study eye or history of any of the following procedures in the study eye prior to Week 1:

• Incisional glaucoma surgery (i.e., glaucoma drainage implant/shunt or trabeculectomy)
• Ocular angle-based surgery (i.e., goniotomy or canaloplasty)
• Minimally Invasive Glaucoma Surgery (MIGS) in the study eye.
• Angle-based glaucoma surgery (e.g., Argon or Selective Laser Trabeculoplasty)
• Any history of IOP elevation related to topical steroid administration in either eye.
• Any history of uveitis or inflammation (grade trace or above) except mild anticipated post operative inflammation that resolved in either eye.
• Any history of treatment with complement inhibitors for geographic atrophy in the study eye.
• Known history of ocular herpes simplex virus, varicella-zoster virus, or cytomegalovirus, including viral uveitis, retinitis, or keratitis in either eye.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 79 центров

• Adverum Clinical Site 245 — Mesa
• Adverum Clinical Site 126 — Phoenix
• Adverum Clinical Site 178 — Phoenix
• Adverum Clinical Site 223 — Phoenix
• Adverum Clinical Site 229 — Scottsdale
• Adverum Clinical Site 242 — Sun City
• Adverum Clinical Site 198 — Springdale
• Adverum Clinical Site 109 — Bakersfield
• … и ещё 71 центр

Идентификаторы

NCT: NCT07482176 · ADVM-022-13

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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