To Study the Efficacy, Safety and Immunogenicity of Aflibercept in Patients with Neovascular (Wet) Age-Related Macular Degeneration (AMD)

Phase 3

Completed

Conditions: Retinal disorders in diseases classified elsewhere,

Registration Number: CTRI/2023/09/057655

Lead Sponsor: Zydus Lifesciences Limited

Brief Summary: This is a randomized, double blind, parallel group, multicenter active comparator study. Eligible participants will be randomized in 2:1 ratio to receive either ZRC-3285 (test aflibercept) or EyleaÂ® (reference aflibercept) in the treatment period.A total of 184 patients with 122 patients in test arm and 62 patients in reference arm will be enrolled in the study.The study will consist of: screening period of up to 28 days, treatment period of 57 days (3 doses) and end of study visit at Day 85 (28 days from end of treatment visit). The total duration of the study will be 113 days.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 184

Inclusion Criteria

Male or female participants aged 50 years (completed) or more at the time of screening 2.
Newly diagnosed, angiographically documented patients with primary or recurrent, active subfoveal (including juxtafoveal) choroid neovascularization (CNV) lesion secondary to neovascular (wet) age related macular degeneration (AMD) in the study eye at Screening.
The area of CNV (classic plus occult component) must be â‰¥50% of the total lesion area in the study eye 4.
Total lesion area <12 Disc Areas (DA) in size (including blood, scars and neovascularization) as assessed by FA in the study eye 5.
BCVA between 20/40 and 20/320 (Snellen equivalent) using Early Treatment Diabetic Retinopathy Study chart (ETDRS) testing in the study eye at Screening and Baseline 6.
Sufficiently clear ocular media and adequate pupillary dilation should be ensured in the patient to permit good quality ocular imaging 7.
Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines.
This must be obtained before the performance of any protocol related procedures that are not part of normal patient care (If the Participant is legal blind or illiterate, an impartial witness should be present during the entire informed consent discussion) 8.
Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.

Exclusion Criteria

Central subfield of the study eye affected by fibrosis or geographic atrophy assessed by color fundus photography at Screening 2.
Total area of subfoveal fibrosis, atrophy or scarring â‰¥50% of the total lesion area in the study eye at Screening 3.
Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye 4.
Any active intraocular inflammation (grade trace or above) in the study eye within 4 weeks prior to Baseline.
5.Known hypersensitivity to aflibercept or any of the components of study medication or EyleaÂ® or to drugs of similar chemical class or to fluorescein or any other component of fluorescein formulation or to topical anesthetics, mydriatic medications.
The patient should not be hypersensitive to any of the drugs, components of the drugs, or essential supportive drugs that are required to be used during treatment or evaluation 6.
Any concomitant or prior treatment with ethambutol (2 weeks prior to randomization); deferoxamine and topiramate (4 weeks prior to randomization); tamoxifen, hydroxychloroquine, chloroquine, or vigabatrin (8 weeks prior to randomization), and amiodarone (12 weeks prior to randomization) 7.
Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days or 5 half-lives prior to Baseline, whichever is longer or is currently enrolled in an investigational study 8.
History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 1 year before Screening or positive test result(s) for alcohol or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines) at Screening if required as per medical history.
9.History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening 10.
History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening.
11.Presence of uncontrolled systolic blood pressure >160 mmHg or uncontrolled diastolic blood pressure >100 mmHg based on the average of 3 readings taken with the patient in a resting state (Patients with controlled blood pressure (<140/90) with stable anti-hypertensive treatment regimen will be eligible).
No history of hypertensive crisis or encephalopathy 12.
Documented medical history of thromboembolic events, stroke, cerebral infarction, or transient ischemic attacks, peripheral vascular disease, unstable angina pectoris, congestive heart failure or recent (within 6 months of screening) myocardial infarction, clinically significant cardiac diseases like New York Heart Association (NYHA) Grade II or greater, uncontrolled atrial fibrillation or any other cardiac arrhythmias 13.
Documented medical history of bleeding disorders, including platelet disorders, acquired or hereditary coagulations disorders, and acquired or hereditary vascular disorders 14.
Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years; carcinoma in situ of the cervix; or malignancy, which is considered cured with minimal risk of recurrence 15.
Any history or evidence of a concurrent intraocular condition in the study eye, including retinal diseases other than neovascular AMD, that in the judgment of the Investigator, could either require medical or surgical intervention during the course of the study to prevent or treat visual loss that might result from that condition or that limits the potential to gain visual acuity upon treatment with the investigational product (e.g. diabetic retinopathy, cataract, uncontrolled glaucoma, uveitis, previous corneal transplant, the refractive error in the study eye does not exceed 8 diopters of myopia, recent cataract surgery etc.) 16.
History of a medical condition (disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding) that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product, affect interpretation of the results of the study, or renders the patient at high risk of treatment complications 17.
Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator 18.
History of gastrointestinal perforation or fistulae, hemorrhage of any kind (e.g. Hemoptysis), arterial or venous thromboembolism, renal disease, history of unhealed wound or ulcers or planned surgery during study conduct period.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of patients who lose fewer than 15 letters (approximately 3 lines) visual acuity	Baseline to Week 12

Secondary Outcome Measures

Name	Time	Method
change in best corrected visual acuity	Baseline to Week 12
Proportion of patients who gain more than 15 letters (approximately 3 lines)	Baseline to Week 12
Incidence of anti-drug antibodies	Baseline & end of study
To evaluate & compare safety and tolerability in participants who are exposed to the investigational medicinal products	Baseline & end of study

Trial Locations

Locations (33): "Shri C. H. Nagri Municipal Eye Hospital "
🇮🇳
Ahmadabad, GUJARAT, India
"Sri Bhagwan Mahavir Vitreo Retina Services Sankara Netralaya"
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Chennai, TAMIL NADU, India
Advance Retina Care
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Ahmadabad, GUJARAT, India
Ambade Eye Hospital
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Nagpur, MAHARASHTRA, India
Belgavi Institute & Medical sciences
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Belgaum, KARNATAKA, India
Department of Ophthalmology, SMS Medical College and Attached Hospitals
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Jaipur, RAJASTHAN, India
Disha Eye Hospital
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Kolkata, WEST BENGAL, India
Dr. Agarwalâ€™s Eye Hospital
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Tirunelveli, TAMIL NADU, India
Dr. Jawahar Lal Rohatgi Smarak Netra Chikitsalaya
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Nagar, UTTAR PRADESH, India
Dr. R. P Centre AIIMS, Delhi
🇮🇳
Delhi, DELHI, India
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"Shri C. H. Nagri Municipal Eye Hospital "
🇮🇳Ahmadabad, GUJARAT, India
DrEkta Patel
Principal investigator
9909288778
drektapatelcr@gmail.com