A Phase Ⅱa Study of the Safety, Tolerability and Efficacy of BD111 in Herpes Simplex Virus Type I Stromal Keratitis

Официальное название

A Multicenter, Single-blind, Single-dose, Randomized, Phase Ⅱa Trial to Evaluate the Safety, Tolerability and Efficacy of Intrastromal BD111 Gene Editing Therapy in Adults With HSV-1 Stromal Keratitis

Обзор

This study aims to compare the clinical efficacy and safety of BD111 injection in combination with standard therapy vs. standard therapy in herpes simplex virus type I stromal keratitis (HSK), providing preliminary confirmation of the clinical effectiveness of BD111 in combination with standard therapy.

Подробное описание

This is a phase Ⅱa, single-blind, single-dose, randomized, positively controlled clinical trial of BD111 in patients with herpes simplex virus type I stromal keratitis (HSK) aged 18 to 70 years. Forty eligible participants will be recruited in the trial. BD111 is investigational new biologics (Injection)--a type of lentiviral-like particle that can simultaneously deliver SpCas9 and gRNA targeting the HSV-1 virus gene, also known as HSV-1-erasing lentiviral particles (HELP). The total follow-up duration was 12 months, the safe endpoints and efficacy endpoints will be used to assess the efficacy, safety and tolerability profiles in patients with HSK.

Вмешательства

• Генная терапия BD111 Injection (investigational new drug)
  BD111: intrastromally injection, single-dosing 10E6 TU/eye, specified injection volume is 0.15mL.
• Комбинированный продукт Triple-drugs therapy of HSV-1 stromal keratitis
  Triple-drugs therapy: "Ganciclovir Eye gel+Valacilovir Tablets+Prednisolone Acetate Eye Drops" for 3 weeks.

Первичные конечные точки

• Clinical cure rate of HSK at Day 70 and Day112 post-administration [Срок оценки: 12 months]

Вторичные конечные точки (12)

• The percentage of participants with successful clearance of HSV-1 viral genome in tears at Day 14, Day 28, Day 70, Day 112, Day 180, and Day 365 post-administration [Срок оценки: 12 months]
• The percentage of participants with failed clearance of HSV-1 viral genome in tears at Day 14, Day 28, Day 70, Day 112, Day 180, and Day 365 post-administration [Срок оценки: 12 months]
• The percentage of participants with HSK recurrence at Day 180, and Day 365 post-administration [Срок оценки: 12 months]
• Score change of corneal inflammation scale post-administration [Срок оценки: 12 months]
• The improvement in best corrected visual acuity (BCVA) [Срок оценки: 12 months]
• The improvement in corrected distance visual acuity (CDVA) post-administration [Срок оценки: 12 months]
• Anti-p24 antibody in blood [Срок оценки: 12 months]
• Anti-Cas9 antibody in blood [Срок оценки: 12 months]
• Anti-BD111 antibody in blood [Срок оценки: 12 months]
• Vector RNA copy number in tear fluid [Срок оценки: 12 months]
• Circular DNA copy number in blood [Срок оценки: 12 months]
• Off-target Detection [Срок оценки: 6 months]

Критерии участия

Inclusion Criteria: Participants must meet all of the following inclusion criteria to be enrolled in this study.

• Aged 18 to 70 years old;
• Clinically diagnosed with herpes simplex virus stromal keratitis;
• Tear swab HSV-1 nucleic acid test (qPCR method) positive;
• No use of systemic antiviral drugs or corticosteroids within 48 hours before enrollment;
• No systemic immune eye diseases;
• Good eyelid structure and blinking function;
• Eye structure and function assessment showing potential for visual recovery;
• No retinal detachment, with generally normal visual function;
• No history of corneal trauma;
• Visual acuity in the fellow eye is better than 20/200;
• Fertile males or females must use highly effective contraceptive methods (such as oral contraceptives, intrauterine devices, abstinence, or barrier contraception combined with spermicides) during the trial and continue contraception for 12 months after administration;
• Participants voluntarily join the study, sign an informed consent form, have good compliance, and cooperate with follow-up visits.

Exclusion Criteria: Patients with any of the following conditions cannot be enrolled in this study

• Active ocular infection caused by other pathogens in the target eye or the fellow eye within 30 days before enrollment, including but not limited to blepharitis, infectious conjunctivitis, keratitis, scleritis, and endophthalmitis;
• Patients with bilateral viral keratitis
• Previous corneal transplant surgery in the study eye;
• A history of adverse reactions or allergies to corticosteroids and sodium fluorescein, allergies to therapeutic or diagnostic protein products, allergies to ≥ two drugs or non-drug factors, or having an ongoing allergic disease;
• Absence of tear film and blinking function;
• Severe dry eye disease;
• Malignant ocular surface tumor;
• Glaucoma;
• Patients with systemic autoimmune diseases;
• Signs of systemic infection before enrollment, including fever and receiving antibiotic treatment (abnormal elevating values in white blood cells, lymphocytes, and neutrophils in routine blood tests);
• Abnormal major organ function or other uncontrolled clinical problems, mainly including but not limited to the following:

• Severe kidney disease history, serum creatinine ≥ 133μmol/L;
• Liver dysfunction, transaminase level ≥ 80 IU/L;
• Uncontrolled hypertension, systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg;
• Uncontrolled diabetes, fasting blood glucose greater than or equal to 8.0 μmol/L;
• Cardiovascular disease history, with arrhythmia, myocardial ischemia, and myocardial infarction (diagnosed by electrocardiogram examination);
• Platelet level ≤ 100×10\^9/μL or ≥ 450×10\^9/μL due to any cause, hemoglobin level lower than 10.0g/dL (male) or 9.0g/dL (female).
• HIV infection;
• Pregnant and lactating women (pregnancy in this trial is defined as a positive urine pregnancy test);
• Participation in other drug or medical device clinical trials;
• Alcohol or drug abuse;
• Lack of compliance with the trial or the ability to sign an informed consent form;
• Other situations deemed unsuitable for participation in the trial by the investigator.

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Eye Hospital of Wenzhou Medical University — Wenzhou

Идентификаторы

NCT: NCT06474442 · BD-HSK-111002-Ⅱa

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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