CTRI/2023/09/057655 [Registered on: 14/09/2023] Trial Registered Prospectively
Last Modified On:
16/05/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group Trial
Public Title of Study
To Study the Efficacy, Safety and Immunogenicity of Aflibercept in Patients with Neovascular (Wet) Age-Related Macular Degeneration (AMD)
Scientific Title of Study
A Phase III, Randomized, Double blind, Parallel Group, Multicenter Study to Compare the Efficacy, Safety and Immunogenicity between Test Aflibercept and Eylea® in Patients with Neovascular (Wet) Age-Related Macular Degeneration (AMD)
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
AFLI.22.001 ,Ver 02 Dated 21 June 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Maulik Doshi
Designation
General Manager
Affiliation
Zydus lifesciences Ltd
Address
Zydus Research Centre,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
Maulik.Doshi@zyduslife.com
Details of Contact Person Scientific Query
Name
Dr Bhargav Darji
Designation
Senior Medical Expert
Affiliation
Zydus lifesciences Ltd
Address
Zydus Research Centre,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
Bhargav.R.Darji@ZydusLife.com
Details of Contact Person Public Query
Name
Dr Bhargav Darji
Designation
Senior Medical Expert
Affiliation
Zydus lifesciences Ltd
Address
Zydus Research Centre,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
Bhargav.R.Darji@ZydusLife.com
Source of Monetary or Material Support
Zydus Lifesciences Ltd.
Zydus Research Centre,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya, Ahmedabad 382213, India
Primary Sponsor
Name
Zydus Lifesciences Limited
Address
Zydus Research Centre,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya, Ahmedabad 382213, India
"Dr. Agarwal’s Eye Hospital Institution Review Board Dr Agarwal’s Eye Hospital No. 10, South Bypass Road Vannarpettai Tirunelveli Tamil Nadu - 627003 India "
Approved
"Ethics Committee S P Medical college, Bikaner S.P. Medical College, Bikaner Pawanpuri, Bikaner Rajasthan - 334003 India"
"IEC – Saishwari Clinic- Hospital for Mental health Yashwant co op Housing Society Sangli, Maharashtra- 416410, India "
Approved
"IEC – Saishwari Clinic- Hospital for Mental health Yashwant co op Housing Society Sangli, Maharashtra- 416410, India "
Approved
"Insight Institute of Ophthalmology - Institutional Ethics Committee Jay Ganesh samrajya, H Wing, Spine Road, 411039"
Approved
"Institutional Ethics Comm ittee Room no- 102, Old OT Block All lndia Institute of Mcdical Sciencos Ansari Nagar. New Delhi-10029. lndia"
Approved
"Institutional Ethics Committee B.J. Medical College and Civil Hospital Office of Medical Superintendent Civil Hospital Ahmedabad Gujarat - 380016 India"
Approved
"Institutional Ethics Committee BIMS Belagavi Institute Of Medical Sciences, Belagavi Dr B R Ambedkar Road Belgaum Belgaum Belagavi (Belgaum) Karnataka - 590001 India"
Approved
"Institutional Ethics Committee Indira Gandhi Institute Of Medical Sciences Sheikhpura,Patna Bihar-800014"
Approved
"Institutional Ethics Committee, BSL Eye Care BSL EYE CARE ROAD NO 2 RAJENDER NAGAR Patna Bihar - 800016 India"
Approved
"Institutional Ethics Committee, NHLIEC Smt. NHL Municipal Medical College V S Hospital Campus, Ellis bridge, Ahmedabad Ahmedabad, Gujarat - 380006 India"
Approved
"Institutional Ethics Committee, SV Sumandeep Vidyapeeth Sumandeep Vidyapeeth At and Post Pipariya Vadodara Gujarat - 391760 India"
Approved
"Institutional Review Board - Ethics Committee Vision Research Foundation New No.41, Old No.18 College Road Nungambakkam Chennai, Tamil Nadu - 600006 India"
Approved
"Kanpur Medical Ethics Committee Dr. Jawahar Lal Rohatgi Hospital 117/52, Dr. Jawahar Lal Rohatgi Hospital, Sarvodaya Nagar, Kanpur, 208005, Uttar Pradesh"
Approved
"Kashyap Memorial eye hospital Ethics Committee The Kashyap Memorial eye hospital Purulia Road Near Dangratoli Chowk Dangartoli, Nayatoli Ranchi Jharkhand - 834001 India"
"S.M.S. Medical College and Attached Hospitals J.L.N. Marg Jaipur, Rajasthan - 302004 India "
Approved
"Sangini Hospital Ethics Committee Sangini Hospital Santorini Square, B/H Abhishree Complex Opp. Star Bazar Nr Jodhpur Cross Roads Satellite Ahmedabad Ahmedabad Gujarat - 380015 India"
Approved
"Sangini Hospital Ethics Committee Sangini Hospital Santorini Square, B/H Abhishree Complex Opp. Star Bazar Nr Jodhpur Cross Roads Satellite Ahmedabad, Gujarat - 380015 India"
Approved
"Sangini Hospital Ethics Committee Sangini Hospital Santorini Square, B/H Abhishree Complex Opp. Star Bazar Nr Jodhpur Cross Roads Satellite Ahmedabad, Gujarat - 380015 India"
Approved
"Shroff Eye Hospital and Vision Research Center 222, S.V. Rd, Near Suburbia Theatre, Bandra (W). Mumbai City Maharashtra - 400050 India"
Approved
Ethics Committee Institutional Review Board Sankara Eye Hospital Varthur Main Road Kundalahalli Gate Bangalore Bengaluru (Bangalore) Rural Karnataka-560037, India
Approved
L V Prasad Eye Institute Ethics Committee , L V Prasad Eye Institute L V Prasad Marg, Road No 2 Banjara Hills Hyderabad Hyderabad, Telangana - 500034
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: H36||Retinal disorders in diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Aflibercept (ZRC-3285)
Dose:2 mg (0.05 mL)
Mode of Administration: intravitreal injection
Frequency :- every 4 weeks via Single use vial
Comparator Agent
Aflibercept(Eylea)
Dose:2 mg (0.05 mL)
Mode of Administration: intravitreal injection Frequency :- every 4 weeks via Single use vial
Inclusion Criteria
Age From
50.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. 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.
3. The area of CNV (classic plus occult component) must be ≥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.
ExclusionCriteria
Details
1. 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 ≥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 Eylea® 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
Proportion of patients who lose fewer than 15 letters (approximately 3 lines) visual acuity
Baseline to Week 12
Secondary Outcome
Outcome
TimePoints
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
Target Sample Size
Total Sample Size="184" Sample Size from India="184" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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 Eylea® (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.