This is a 96-week, Multicenter Study in Patients With Neovascular AMD That Evaluates OCUL101 for Efficacy, Safety, Durability, and Pharmacokinetics, Comparing it With Another Treatment. The Study Will be Conducted in Two Parts, Part A and Part B.

Официальное название

A Phase II/III Multicenter, Randomized, Masked, Active Comparator-Controlled Study to Evaluate the Safety and Efficacy of Two Doses of OCUL101, an Anti-VEGF and Anti-Complement C5, Bi-specific Humanized Antibody-Like "Trap" in Participants With Neovascular Age-Related Macular Degeneration With or Without Geographic Atrophy - STAT Study

Обзор

Oculgen has begun a study of an investigational drug called OCUL101 as a possible treatment for neovascular AMD. An investigational drug is one that has not been approved by regulatory agencies, such as the Food and Drug Administration (FDA) in the United States (US), the European Medicines Agency (EMA) in the European Union (EU), or others. A comparator drug, Eylea® (aflibercept), will also be used in this study. Aflibercept is approved by regulatory agencies to treat neovascular AMD. VEGF-A (vascular endothelial growth factor A) is a protein released by the body in response to certain conditions that encourages the eye to form new blood vessels that are weak and leaky. This can lead to leakage of fluid and swelling in the macula; the part of the eye that helps you see clearly. C5 (component 5) is a part of the immune system released when there is ongoing damage to the eye such as when you have neovascular AMD. When it becomes too active in the eye, it can cause inflammation and further damage, leading to thinning of the back of the eye, a condition called geographic atrophy (GA). OCUL101 works by blocking both VEGF-A and C5. The main purpose of this study is to see how safe and tolerable OCUL101 is and how well OCUL101 works in participants when compared with aflibercept. From here on, OCUL101 and aflibercept will be referred to as the "study drug." This study is divided into 2 periods: a screening period and a study treatment period. During each study period, you will have 1 or more visits with your study doctor at the center. The screening visit will last about 3 hours, and all other visits will last about 3 to 6 hours. This study has 2 Parts. Part A uses the 10.4 mg dose of OCUL101 and Part B uses 2 doses of OCUL101 (6.5 mg and 10.4 mg) to compare with 2 mg of aflibercept. Before any study-related tests and procedures can be done, you will be asked to read and sign this informed consent form, and then the study will begin with a screening visit. The purpose of the screening visit is to decide whether or not you meet the requirements to take part in this study. If you do not meet the requirements, the study doctor will explain why and will discuss other treatment options with you. If the study doctor decides that you meet all of the requirements to be in this study, you will be assigned to either Part A or randomly assigned (like drawing straws) to one of the groups in Part B. You will then receive one of the following study treatment plans: * Part A, 10.4 mg of OCUL101 * Part B, Group 1, 6.5 mg of OCUL101 + as needed study treatments of 10.4 mg OCUL101 * Part B, Group 2, 10.4 mg of OCUL101 * Part B, Group 3, 10.4 mg of OCUL101 * Part B, Group 4, 2 mg of aflibercept You will receive 3 injections between Day 1 and Week 8, after which you may or may not receive additional injections every 8 weeks until Week 36. After you receive the set number of injections for your Part/group, you may receive additional injections during the study if the study doctor thinks it will help you. You will have an 80% (4 in 5) chance of receiving OCUL101 and a 20% (1 in 5) chance of receiving aflibercept. This is a double-masked study, which means you and some of the people involved in the study will not be told if you are receiving OCUL101 or aflibercept. However, this information will be given to the study doctor if it becomes necessary for your safety. The eye receiving the study drug is called "the study eye". If the other eye, called the "fellow eye", needs treatment with anti-VEGF therapy, you can discuss this with your study doctor. This treatment may be provided during your study visit, if appropriate. Description of the procedures and assessments * Medical history: Includes questions about any diseases, chronic or ongoing conditions, surgeries, cancer history, reproductive status, and smoking history. Any information about current or previous medicines will also be recorded. * Demographics: Information to be collected includes age, sex, and race/ethnicity. * Physical examination: Physical examination of the chest, abdomen, head and neck, and musculoskeletal system will be done as per your study doctor's preferred methods. * Eye examinations: Throughout the study you will have several eye tests. Both the front and back of your eye will be examined and some of these eye exams may occur in both eyes. Eye drops may be used to make your pupils (center part of your eye) look larger (dilated) and easier to look through. * BCVA: You will sit in front of an eye chart to read the letters and test the sharpness and accuracy of your vision. * Contrast sensitivity: You will sit in front of an eye chart read the letters where the letters are lighter and darker shades. * Color Vision Testing: Your vision will be tested to see how well you see color by having you look at color vision charts. * Assessment of metamorphopsia: Metamorphopsia is when you see lines as wavy or bent instead of straight.

Вмешательства

• Препарат bispecific anti-VEGF and anti-complement
  Administered via injection.

Первичные конечные точки

• Part A: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). [Срок оценки: From enrollment to the end of treatment up to week 36, followed by assessment visits every 8 weeks and PRN treatment until the end of study (Week 96)]
• Part B: Change from baseline in mean BCVA score. [Срок оценки: From enrollment followed by injection and assessments visits every 8 weeks and PRN treatment until the end of study (Week 96).]

Вторичные конечные точки (6)

• Part A: Change in baseline in mean BCVA score. [Срок оценки: From enrollment until week 16]
• Part A: Change from Baseline in mean central subfield macular thickness (CST). [Срок оценки: From enrollment to end of treatment at week 96.]
• Part B: Mean change from baseline in CST. [Срок оценки: From enrollment to Week 36.]
• Part B: Proportion of participants with greater than or equal to 15-letter improvement in BCVA from baseline. [Срок оценки: From enrollment to Week 36.]
• Part B: Percent change in CNV lesion size vs aflibercept. [Срок оценки: From enrollment to Week 96.]
• Part B: Change in square root of GA lesion size. [Срок оценки: From enrollment to Week 96.]

Критерии участия

Критерии включения

• Participants must meet all the following criteria to be eligible for this study:

• Signed Informed Consent
• Age ≥50 and ≤89 years on Day 1/Baseline
• Treatment-naive CNV secondary to AMD (nAMD), with or without geographic atrophy in the study eye.

a. Patients with neovascular AMD alone include: i. All MNV subtypes (Type 1, Type 2, Type 3, PCV). (Spaide 2020) ii. Subfoveal CNV or juxtafoveal CNV with a subfoveal component related to the CNV activity identified by FA or OCT (where CNV activity is defined as showing evidence of subretinal fluid, subretinal hyper reflective material, or leakage) iii. A total lesion size (including blood, atrophy, fibrosis, and neovascularization) of ≤ 9 disc areas on FA iv. A CNV component area of ≥50% of the total lesion size on FA b. Participants with nAMD and underlying and quantifiable geographic atrophy (GA) will be included if the following criteria are met: i. Total GA area on FAF between ≥2.5mm² and ≤17. mm² (\~1-7 disc areas), If GA is multifocal, at least one lesion ≥1.25 mm² (\~0.5 disc area).

ii. GA lesion must be located within 1500 μm of the foveal center but not involving the fovea

• BCVA of 70 to 24 letters, inclusive (20/40 to 20/320 approximate Snellen equivalent), using the ETDRS protocol (see the BCVA manual for additional details) at Screening and Baseline in the study eye
• Participants with confirmed underlying geographic AMD in the study eye at Screening or Baseline will be included in the study if all of the other criterion are met
• Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm diagnosis in the study eye
• Male participants engaged in a sexual relationship with a woman of childbearing potential must be willing to use a medically accepted method of contraception from the duration of their participation in the study.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive measures that result in failure rate <1% per year during the treatment period and for at least 3 months after the final dose of study treatment i. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements ii. Examples of acceptable contraceptive methods include bilateral tubal ligation, male sterilization; hormonal contraceptives that inhibit ovulation, hormone releasing intrauterine devices; and copper intrauterine devices iii. Contraception methods that do not result in a failure rate of <1% per year such as male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide are not acceptable iv. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participants. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception

Критерии исключения

• Participants who meet any of the following criteria will be excluded from study entry:

• CNV due to causes other than AMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, or uveitis in either eye.
• Any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye.
• Presence at screening of central serous chorioretinopathy in the study eye.
• Retinal pigment epithelial tear involving the macula.
• On FA/CFP/OCT/FAF: Inactive nAMD in the study eye:

• Subretinal hemorrhage of >50% of the total lesion area and/or that involves the fovea
• Fibrosis of >50% of the total lesion area and/or that involves the fovea
• Cystic degeneration (persistent intraretinal fluid or tubulations unresponsive to treatment)
• Any concurrent intraocular condition (e.g., amblyopia, aphakia, retinal detachment, cataract, diabetic retinopathy or maculopathy, or epiretinal membrane with traction) that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study in the study eye.
• Current vitreous hemorrhage at Screening and Day 1 in the study eye.
• Uncontrolled glaucoma, defined as intraocular pressure >25 mmHg while on two or more pressure lowering medications and/or will require surgical intervention or laser treatment during the study in the study eye.
• Spherical equivalent of refractive error demonstrating more than 8 diopters of myopia in the study eye.
• For participants who have undergone prior refractive or cataract surgery, the preoperative refractive error should not have exceeded -8 diopters of myopia in the study eye.
• Any prior or concomitant treatment for CNV, GA or vitreomacular-interface abnormalities, including, but not restricted to, IVT treatment (e.g., anti-VEGF, complement therapy, steroids, tissue plasminogen activator, ocriplasmin, C3F8, air), periocular pharmacological intervention, argon laser photocoagulation, verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or ocular surgical intervention in the study eye.
• Any cataract surgery or treatment for complications of cataract surgery with steroids or YAG (yttrium-aluminum-garnet) laser capsulotomy within 3 months prior to Screening in the study eye
• Any other intraocular surgery or intervention (e.g., pars plana vitrectomy, glaucoma surgery, including minimally invasive glaucoma surgery \[MIGS\], corneal transplant, or radiotherapy)
• Non-functioning non-study eye, defined as either:

• BCVA of hand motion or worse
• No physical presence of non- study eye (i.e., monocular)
• History of idiopathic or autoimmune-associated uveitis in either eye
• Active ocular inflammation or suspected or active ocular or periocular infection in either eye at the Screening visit.
• Any major illness or major surgical procedure within 1 month before screening 28 Clinical Protocol OCUL101-002 Shenzhen Oculgen Biomedical Technology Co., Ltd. Protocol OCUL101-002, Version 2.0 Date: 12March2026
• Active cancer within the 12 months prior to Screening except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of < 6 and a stable prostate-specific antigen for > 12 months
• Requirement for continuous use of any medications and treatments indicated in Section 6.6.1, Prohibited Therapy
• Systemic treatment for suspected or active systemic infection at Screening.

a. Ongoing use of prophylactic antibiotic therapy may be acceptable if approved after discussion with the Medical Monitor

• Uncontrolled blood pressure, defined as systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg while a participant is at rest at the Screening visit.

a. If a participant's initial reading exceeds these values, a second reading may be taken later on the same day or on another day during the screening period. If the participant's blood pressure is controlled by antihypertensive medication, the participant should be taking the same medication continuously for at least 30 days prior to Screening.

• Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Screening.
• History of other disease, metabolic dysfunction, physical examination finding, or historical or current clinical laboratory findings giving reasonable suspicion of a condition that contraindicates the use of the investigational drug or that might affect interpretation of the results of the study or renders the participant at high risk for treatment complications in the opinion of the investigator
• Pregnancy or breastfeeding, or intention to become pregnant during the study

a. Women of childbearing potential must have a negative urine pregnancy test result within 28 days prior to initiation of study treatment. If the urine pregnancy test is positive, it must be confirmed by a serum pregnancy test.

• History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of OCUL101 or aflibercept injections, study-related procedure preparations (including fluorescein), dilating drops, or any of the anesthetic and antimicrobial preparations used by a participant during the study
• Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals), including gene therapy or cell therapies, within 3 months prior to Screening.

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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07520318 · OCUL101-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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