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CTRI Number  CTRI/2019/03/018322 [Registered on: 29/03/2019] Trial Registered Prospectively
Last Modified On: 09/03/2022
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Biological 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Clinical trial to compare effects and safety of Lupins Ranibizumab with Lucentis® in Patients with Age-Related loss of central vision. 
Scientific Title of Study   A Prospective, Randomized, Parallel Group, Double Blind, Multicenter Study to Compare the Efficacy, Safety & Immunogenicity of Lupin’s Ranibizumab with Lucentis® in Patients with Neovascular Age-Related Macular Degeneration 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
LRP/RBZ/2015/002 V1.1 02 Aug 2018  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Chirag Shah 
Designation  Associate Director 
Affiliation  Lupin Limited 
Address  1st Floor, A Wing Green Bldg, NDDD Dept. Survey No. 46 A / 47 A, Village Nande, Taluka Mulshi, Pune, Maharashtra, India Pune MAHARASHTRA 412115 India

Pune
MAHARASHTRA
412115
India 
Phone  020-66749068  
Fax    
Email  chiragshah@lupin.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Dhananjay Bakhle 
Designation  Executive Vice President 
Affiliation  Lupin Limited 
Address  LRP, Old Building, 2nd Floor, Dept. NDDD, Survey No. 46 A / 47 A, Village Nande, Taluka Mulshi, Pune, Maharashtra, India Pune MAHARASHTRA 412115 India

Pune
MAHARASHTRA
412115
India 
Phone  020-66749054  
Fax    
Email  dhananjaybakhle@lupin.com  
 
Details of Contact Person
Public Query
 
Name  Dr Dhananjay Bakhle 
Designation  Executive Vice President 
Affiliation  Lupin Limited 
Address  LRP, Old Building, 2nd Floor, Dept. NDDD, Survey No. 46 A / 47 A, Village Nande, Taluka Mulshi, Pune, Maharashtra, India Pune MAHARASHTRA 412115 India

Pune
MAHARASHTRA
412115
India 
Phone  020-66749054  
Fax    
Email  dhananjaybakhle@lupin.com  
 
Source of Monetary or Material Support  
Lupin Limited Biotechnology Division, Gate No:1156, Village-Gotawade, Taluka-Mulshi, Pune-412115 Maharashtra- India 
 
Primary Sponsor  
Name  Lupin Limited Biotechnology Division 
Address  Gate No:1156, Village-Gotawade, Taluka-Mulshi, Pune-412115 Maharashtra- India 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 32  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Saurav Sinha  B B Eye Foundation  Shree Tower , RAA-36 Ragunathpur, VIP Road, Kolkata-700059
Kolkata
WEST BENGAL 
9831808203

drssinharesearch@gmail.com 
Dr Sanjeevani Ambekar  B J Government Medical College and Sassoon General Hospital  OPD 69 Department of Ophthalmology B J Government Medical College and Sassoon General Hospital Jaiprakash Narayan Road Near Pune Railway Station
Pune
MAHARASHTRA 
9049784962

sanjeevani_ambekar@yahoo.com 
Dr Alay S Banker  Bankers Retina Clinic & Laser Centre  5, Subhash Society, Behind Ishwar Bhuvan,Near H.L. Commerce Six Roads, Navrangpura, Ahmedabad - 380009, Gujrat
Ahmadabad
GUJARAT 
9825024655

alay.banker@gmail.com 
Dr Nita Shanbhag  D Y Patil Medical College & Hospital  Sector 5, Nerul, Navi Mumbai, Maharashtra 400706
Mumbai
MAHARASHTRA 
9322402424

nita.eye@gmail.com 
Dr Nitin Prabhudesai  Deoyani hospital  Plot no.121, Lane no.4, Dhanurkar colony, Kothrud, Pune-411038, Maharashtra
Pune
MAHARASHTRA 
9762007699

ngpmedha@gmail.com 
Dr Anup Shah  Dhadiwal Hospital  Opp. New CBS, Trambakeshwar Rd, Matoshree Nagar, Nashik, Maharashtra 422002
Nashik
MAHARASHTRA 
9850501495

navkar.eye@rediffmail.com 
Dr M A Rani Sujatha  Dr B R Ambedkar Medical College and Hospital  Kadugondanahalli Bengaluru Karnataka 560045
Bangalore
KARNATAKA 
9845747518

drranisujatha@gmail.com 
Dr Virendra Agrawal  Dr. Virendra Laser, Phaco Surgery Center  Tonk Phatak, Behind Toyota car showroom, Tonk road, Gandhi nagar, Jaipur- 302015, Rajasthan
Jaipur
RAJASTHAN 
9314017147

drvirendra@yahoo.com 
Dr Deepika Singhal  GMERS Medical College and Civil Hospital   225, Sola Rd, Beside High Court, Shenbhai Nagar, Sola, Ahmedabad, Gujarat 380081
Ahmadabad
GUJARAT 
9426541167

deepika1103@yahoo.com 
Dr Raju Sampangi  Gurushree Hi-Tech Multispeciality Hospital  Gurushree Hi-Tech Multispeciality Hospital, No.1558, Opp. Chandra Layout Bus Stand, Chandra Layout, Vijaynagar, Bengaluru, Karnataka 560040
Bangalore
KARNATAKA 
9880448422

rajusampangi@gmail.com 
Dr Amit Nene  Isha Netralaya  Radha Krishna sankul, Opp. Holy Cross Hospital, Karnik Rd, Kalyan West, Maharashtra 421301
Thane
MAHARASHTRA 
9321013241

amitnene9@gmail.com 
Dr Aniruddha Nalgirkar  Kamalnayan Bajaj Hospital  Gut No 43., Bajaj Marg Beed Bypass Road, Satara Parisar, Aurangabad, Maharashtra 431005
Aurangabad
MAHARASHTRA 
9822864268

nalgirkar@rediffmail.com 
Dr Ashish Saxena  Kanoria Hosiptal and Research Centre  Kanoria Hospital and Research Centre, Airport-Gandhinagar Highway, Village: Bhat, Dist. Gandhinagar, North Gujarat, 382428
Gandhinagar
GUJARAT 
9824042699

drashishsaxenacr@gmail.com 
Dr Gaurav Paranjpe  Krishna Institute of Medical Sciences Deemed University  Pune- Bangalore highway, NH-4, Malkapur, Karad-415110, Maharashtra
Satara
MAHARASHTRA 
9764812911

gaurav65@yahoo.com 
Dr Usha Palekar  Lifepoint Multispecialty Hospital   Sr. No.145, 1, Mumbai Pune Bypass Road Near Hotel Sayaji, Wakad, Pune- 411057, Maharashtra
Pune
MAHARASHTRA 
8446974945

dr.ushanikumbh@yahoo.com 
Dr Tapas Ranjan Padhi  LV Prasad Eye Institute  Mithu Tulsi Chanrai Campus, Patia Rd, Bhubaneswar, Odisha 751024
Khordha
ORISSA 
9438361078

tapas@lvpei.org 
Dr Kalpit Shah  M&J Institute of Opthalmology  M&J Institute of Opthalmology, B J Medical College, Asarwa, Ahmedabad, Gujarat 380016
Ahmadabad
GUJARAT 
9825296016

dr_kps@yahoo.co.uk 
Dr Keshav Satish  Mysore Medical College and Research Institute  Irwin Road, Next to Railway Staion, Mysuru, Karnataka 570001
Mysore
KARNATAKA 
9886400414

drsatishkeshav@gmail.com 
DrNaresh Kumar Yadav  Narayana Nethralaya  121/C, West Of Chord Road, Rajaji Nagar, 1st R Block, Bengaluru, Karnataka 560010
Bangalore
KARNATAKA 
9980872120

vasudha.naresh@gmail.com 
Dr Kishor Pahuja  Natasha Eye care  Sai Saheb Society, Shiv Sai Lane, Pimple Saudagar, Pune- 411027
Pune
MAHARASHTRA 
9890086862

kishorepahuja@gmail.com 
Dr Sribhargava Natesh  Nethra Eye hospital  8, Poojary Layout, 80 Feet Road, RMV 2nd Stage, Sanjayanagar, Bangalore 560094
Bangalore
KARNATAKA 
9342880273

sribhargava.natesh@gmail.com 
Dr Samyak Mulkutkar  P D Hinduja Hospital  SVS Rd, Asavari, Mahim, Mumbai, Maharashtra 400016
Mumbai
MAHARASHTRA 
7045833867

samyak.malkutkar@gmail.com 
Dr Ramandeep Singh  Postgraduate Institute of Medical Education and Research (PGIMER)  Postgraduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012
Chandigarh
CHANDIGARH 
9463001620

mankoo95@yahoo.com 
Dr Lakshmi Kanta Mondal  Regional Institute of Ophthalmology  88, College Street, Kolkata- 700073, West Bengal
Kolkata
WEST BENGAL 
033-22123767

lakshmi.mondal62@gmail.com 
DrBiju John C  Regional institute of opthalmology  Regional institute of ophthalmology, Palayam - Airport Rd, Jai Vihar, Kunnukuzhy, Thiruvananthapuram, Kerala 695035
Thiruvananthapuram
KERALA 
09349351689

bijujc@gmail.com 
Dr Rohan Chauhan  Rising Retina Clinic  Rising Retina Clinic, 312-313, Iscon Centre, Shivranjani, Cross Roads, Satellite,Ahmedabad, Gujarat, 380015.
Ahmadabad
GUJARAT 
9825203022

rohan_28782@yahoo.co.in 
Dr Pramod Bhende  Sankara Nethralaya  No. 41, Old 18, College Rd, Thousand Lights West, Nungambakkam, Chennai, Tamil Nadu 600006
Chennai
TAMIL NADU 
7667606388

drpb@snmail.org 
Dr Sharad Bhomaj  Shanti Saroj Netralay  A N Gaikwad 901/902, Beside Sundar Nagar, Anand Nursing home, Off Sangli-Miraj Road, Miraj- 416410
Sangli
MAHARASHTRA 
9960516364

sharadbhomaj@gmail.com 
Dr Mudit Tyagi  Smt. Kanuri Santhamma Retina Vitreous Centre & L.V.Prasad Eye Institute, Hyderabad  Kallam Anji Reddy Campus L V Prasad Marg, Banjara Hills Hyderabad 500 034
Hyderabad
TELANGANA 
91-9553339042

drmudittyagi@gmail.com 
Dr Punit Singh  Sumandeep Vidyapeeth  Medical College, At & Po Pipariya, Taluka Waghodia, Near Shah, Vadodara, Gujarat 391760
Vadodara
GUJARAT 
9879946599

punitsinghdr@yahoo.com 
Dr Jatinder Singh  The Eye Foundation  NO 582 A D B ROAD, COIMBATORE 6410002 TAMILNADU
Coimbatore
TAMIL NADU 
91-9487741561

drjati@gmail.com 
Dr Amol Wankhede  Tulsi Eye Hospital  Gulshan Colony, Nashik, Maharashtra 422214
Nashik
MAHARASHTRA 
9890798969

docamol@hotmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 31  
Name of Committee  Approval Status 
B B Eye Foundation VIP Ethics Committee  Approved 
Ethics Committee, L V Prasad Eye Institute, Bhubaneswar  Approved 
Ethics Committee, L V Prasad Eye Institute, Hyderabad  Approved 
Ethics Committee, Nirmaya Hospital  Approved 
Human Ethics Committee, Regional institute of Ophthalmology   Approved 
Institutional Ethics Comimittee, Isha Netralaya  Approved 
Institutional Ethics Comimittee, Kamalnayan Bajaj Hospital  Approved 
Institutional Ethics Comimittee, P D Hinduja Hospital  Submittted/Under Review 
Institutional Ethics Comimittee, PGIMER  Approved 
Institutional Ethics Committee B J Medical College and Sassoon General Hospital, Pune  Approved 
Institutional Ethics Committee Dr B R Ambedkar Medical College and Hospital  Approved 
Institutional Ethics Committee of Krishna Institute of Medical Sciences, Karad  Approved 
Institutional Ethics Committee of Vision Research Foundation  Submittted/Under Review 
Institutional Ethics Committee Saishwari Clinic Hospital for Mental Health, Miraj  Approved 
Institutional Ethics Committee, Dr. Virendra Laser Phaco Surgery Center, Jaipur  Approved 
Institutional Ethics Committee, Mysore Medical College and Research Institute  Approved 
Institutional Ethics Committee, Padmashree Dr D Y Patil Medical College, Hospital & Research Center  Approved 
Institutional Ethics Committee, Regional Institute of Ophthalmology Kolkata  Approved 
Institutional Ethics Committee, Sumandeep Vidyapeeth  Approved 
Institutional Ethics Committee,Gurushree Hi-Tech Multi Speciality Hospital   Approved 
Instiutional Ethics Committee GMERS Medical College and Civil Hospital  Submittted/Under Review 
Konoria Ethics Committee  Approved 
Lifepoint Research Ethics Committee, Pune  Approved 
Lifepoint Research Ethics Committee, Pune  Approved 
Medilink Ethics Committee  Approved 
Narayana Health Medical Ethics Committee  Submittted/Under Review 
Sangini Hospital Ethics Committee  Submittted/Under Review 
Shree Institutional Ethics Committee, Dhadiwal Hospital  Approved 
The Ethics Committee of the Eye Foundation, Coimbatore  Approved 
The Institutional Ethics Committee B J Medical College and Civil Hospital Ahmedabad  Approved 
Yash Societys Sujata Birla Hospital Ethics Committee  Submittted/Under Review 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: H353||Degeneration of macula and posterior pole,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Lucentis®  Lucentis® supplied as single-use, 2-cc glass vial containing 2.3 mg of ranibizumab in 0.23 mL solution designed to deliver 0.05 mL of 10 mg/mL ranibizumab. Dose of 0.5 mg.Intravitreal injection in the study eye of patients Total three injections per patient; Once monthly. The total study duration is 3.5 months (screening period of 14 days and treatment duration is of 3 months). 
Intervention  Lupin’s Ranibizumab   Lupin’s Ranibizumab supplied as single-use, 2-cc glass vial containing 2.3 mg of ranibizumab in 0.23 mL solution designed to deliver 0.05 mL of 10 mg/mL ranibizumab. Dose of 0.5 mg. Intravitreal injection in the study eye of patients. Total three injections per patient; Once monthly. The total study duration is 3.5 months (screening period of 14 days and treatment duration is of 3 months). 
 
Inclusion Criteria  
Age From  50.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1.Ambulatory male or female participants with age ≥ 50 years at the time of screening who are capable of understanding and giving written informed consent.
2.Primary or recurrent active choroidal neovascularization (CNV) lesions involving the foveal centre secondary to age-related macular degeneration in any one of the eye. (If both eyes are affected and eligible patient and study ophthalmologist will select one eye for study purpose).
3.Best corrected visual acuity in the study eye using ETDRS testing between 20/ 40 and 20/ 320 (Snellen equivalent) both inclusive before pupil dilation.
4.Females who are of non-child bearing potential (surgically sterile or menopausal) OR if of child bearing potential using effective birth control and non-pregnant & non-lactating.
 
 
ExclusionCriteria 
Details  Patients who meet any of the following criteria should be disqualified from entering the study:
1. Known hypersensitivity to ranibizumab or any of the components of study medication.
2. Allergy to fluorescein dye.
3. Patients with coexisting CNV lesions secondary to AMD in the non-study eye that would require simultaneous treatment with anti-VEGF therapies during the study period.

Ocular Conditions of the study eye:

4. Any other pathology involving the CNV lesion like retrofoveolar atrophy or permanent structural damage to fovea or fibrosis/ hemorrhage involving fovea > 50 % of lesion area of study eye that can affect the efficacy of drug.
5. Vitreous hemorrhage or history of rhegmatogenous retinal detachment, retinal pigment epithelial tear involving the macula or macular hole (stage 3 or 4) in the study eye.
6. Aphakia or absence of the posterior capsule in the study eye.
7. Uncontrolled glaucoma as evident by progressive damage to optic nerve or visual fields despite optimum therapy; or steroid-induced glaucoma with continued use of steroids that requires IOP-lowering treatment.
8. H/o serious complications following surgery in the study eye within 1 year prior to randomization.


Concomitant Medications/ Treatments & Procedures:

9. Previous treatment with intravenous Bevacizumab (Avastin®), or intravitreal Ranibizumab (Lucentis®), Bevacizumab (Avastin®), Aflibercept (Eylea®), Pegaptanib (Macugen®) in either of the eyes.
10. Previous external beam radiation or subfoveal focal laser photocoagulation/ thermal laser or transpupillary thermotherapy in the study eye within 5 years prior to randomization.
11. Previous treatment with verteporfin photodynamic therapy (PDT), thermal laser, transpupillary thermotherapy, intravitreal or protein kinase C inhibitors or other AMD therapy in the study eye within 3 months prior to randomization.
12. Previous treatment with intravitreal ocular or periocular steroids (e.g., triamcinolone, anecortave acetate) or intravitreal or peribulbar steroid in the study eye within past 3 months.
13. Concurrent use of systemic anti-VEGF agents.
14. History of vitrectomy, submacular surgery or other surgical intervention for AMD, corneal transplant or any device implantation in the study eye.
15. Intraocular surgery (including cataract surgery) in the study eye within 2 months prior to randomization.
16. Concurrent treatment with an investigational drug or device in the non-study eye.
17. Previous participation in any studies of investigational drugs within 30 days or as prescribed in that study (whichever is later) preceding the initial study treatment.

Other Ocular Conditions:

18. CNV in the study eye due to causes other than AMD such as histoplasmosis, trauma, or pathological myopia etc. or CNV lesion not likely to respond to ranibizumab.
19. Active or ongoing ocular infection (e.g. infectious conjunctivitis, keratitis, scleritis, or endophthalmitis) or severe inflammation in either of the eyes.
20. Any concurrent intraocular condition in the study eye that could either require medical or surgical intervention during the 3 month study period or that could contribute to a loss (of at least 2 Snellen equivalent lines) of best corrected visual acuity over the 3 months study period (e.g. diabetic retinopathy, progressive retinal disease or retinal pathology, cataract, glaucoma, uveitis, previous corneal transplant, the refractive error more than -8 diopters of myopia etc.). The decision regarding exclusion is to be based on the opinion of the investigator.

General Conditions:
21. Patients with seropositivity for hepatitis B, hepatitis C, HIV antibody, syphilis tests or any immunodeficiency and/ or immunosuppressive disease or active systemic infection.
22. History or presence of concurrent systemic diseases or dysfunctions requiring significant medical/ surgical intervention during study period that might affect interpretation of the results or contraindicates the use of ranibizumab or render the subject at high risk for treatment complications based on the Investigator’s judgment such as:
• Cardiovascular disease (e.g. stroke, myocardial infarction), uncontrolled respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic (e.g. optic neuropathy), metabolic, pulmonary, autoimmune disease or psychiatric disease based on previous history and relevant reports of clinical examination, laboratory tests, or ECG etc.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
Proportion of patients losing fewer than 15 letters (approximately 3 lines) from baseline Best Corrected Visual Acuity (BCVA) in the study eye at the end of 3 months, assessed with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.   At the end of 3 months 
 
Secondary Outcome  
Outcome  TimePoints 
Efficacy:
Mean change in Best Corrected Visual Acuity (BCVA) from baseline in the study eye at the end of 3 months.
 
At the end of 3 months 
Safety:
Adverse Events (AE) assessment
Ophthalmic examination
Physical & systemic examination
Vital signs
ECGs
Laboratory parameters: Blood (hematology & biochemistry) and urinalysis
Systemic VEGF inhibition
 
Screening visit to end of study visit 
Immunogenicity:
Proportion of patients with anti-drug antibodies.
 
Day 1 Day 31 Day 90 
 
Target Sample Size   Total Sample Size="200"
Sample Size from India="200" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   15/04/2019 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details   Nil 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary
Modification(s)  

This is a randomized, comparative, parallel group, two arm, double blind, multi-center Phase 3 clinical study. The objective of the study is to compare the efficacy, safety and immunogenicity of Lupin’s Ranibizumab to that of Lucentis® in patients with neovascular age-related macular degeneration.


Results:

This study has been completed. The results of this study showed that Lupin’s ranibizumab demonstrates therapeutic equivalence to Lucentis in terms of changes in best corrected visual acuity (BCVA) measured in terms of proportion of patients losing fewer than 15 letters from baseline as well as mean change in BCVA from baseline in patients with neovascular age-related macular degeneration. Furthermore, Lupin’s Ranibizumab demonstrated comparable safety and immunogenicity profile. Lupin’s Ranibizumab has received marketing authorization on 02 November 2021 by CDSCO



 
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