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CTRI Number  CTRI/2020/09/027629 [Registered on: 07/09/2020] Trial Registered Prospectively
Last Modified On: 10/03/2022
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Biological 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   A study to compare the Efficacy, Safety and Immunogenicity of Sun’s Ranibizumab with Reference Biologic in Patients with Neovascular Age-related Macular degeneration (wet AMD) 
Scientific Title of Study   A Phase III, Comparative, Double Blind, Randomized, Multi-centric study to compare the Efficacy, Safety and Immunogenicity of Sun’s Ranibizumab with Reference Biologic in Patients with Neovascular Age-related Macular degeneration (wet AMD) 
Trial Acronym   
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
ICR/19/009; Version No. 2.1, Dated 30/APR/2021  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Dr Lalit Lakhwani 
Designation  AVP and Head-India Clinical Research 
Affiliation  Sun Pharma Laboratories Limited 
Address  Sun House, Plot No. 201 B/1, Western Express Highway, Goregaon (E), Mumbai-400063, Maharashtra, India India

Mumbai (Suburban)
MAHARASHTRA
400063
India 
Phone  02243244324  
Fax  02243244343  
Email  lalit.lakhwani@sunpharma.com  
 
Details of Contact Person
Scientific Query

Modification(s)  
Name  Dr Piyush Patel 
Designation  Deputy General Manager – India Clinical Research 
Affiliation  Sun Pharma Laboratories Limited 
Address  Sun House, Plot No. 201 B/1,Western Express Highway, Goregaon (E),Mumbai - 400 063, Maharashtra, India.

Mumbai (Suburban)
MAHARASHTRA
400063
India 
Phone  02243244324  
Fax  02243244343  
Email  piyush.patel5@sunpharma.com  
 
Details of Contact Person
Public Query

Modification(s)  
Name  Rajesh Gaikwad 
Designation  Deputy General Manager – India Clinical Research  
Affiliation  Sun Pharma Laboratories Limited 
Address  Sun House, Plot No. 201 B/1,Western Express Highway, Goregaon ( E),Mumbai 400 063

Mumbai
MAHARASHTRA
400063
India 
Phone  02243244324   
Fax  02243244343  
Email  rajesh.gaikwad@sunpharma.com  
 
Source of Monetary or Material Support  
Sun Pharmaceutical Industries Limited Sun House, 201 B/1, Western Express Highway, Goregaon ( E),Mumbai 400 063  
 
Primary Sponsor  
Name  Sun Pharmaceutical Industries Limited 
Address  Sun House, 201 B/1, Western Express Highway, Goregaon ( E),Mumbai 400 063  
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 22  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Natasha Radhakrishnan  Amrita Institute of Medical Sciences and Research Centre, AlMS  Amrita Institute of Medical Sciences and Research Centre, AlMS-Ponekkara. P.O.. Kochi -682041, Kerala, India
Ernakulam
KERALA 
9496389999

natashar@aims.amrita.edu 
Dr Kim Ramasamy  Aravind Eye Hospital & Postgraduate Institute of Opthalmology  Aravind Eye Hospital & Postgraduate Institute of Opthalmology, No. 1, Anna Nagar, Madurai, 625020, Tamilnadu, India
Madurai
TAMIL NADU 
9443067272

kim@aravind.org 
Dr Narendran Venkatapathy  Aravind Eye Hospital & Postgraduate Institute of Opthalmology  Aravind Eye Hospital & Postgraduate Institute of Ophthalmology, Avinashi Road, Coimbatore, 641014, Tamil nadu, India
Coimbatore
TAMIL NADU 
9443357891

narendran@cbe.aravind.org 
Dr Nikumbh Usha Subhash  B.J.Govt .Medical College And Sassoon General Hospital  OPD no. 69,1st Floor, Department of Ophthalmology,B.J.Govt .Medical College And Sassoon General Hospital,Pune-411001
Pune
MAHARASHTRA 
8446974945

dr.ushanikumbh@yahoo.com 
Dr Rohit Sanjay Laul  Chopda Medicare & Research Centre Pvt. Ltd  Mezzanine floor,consulting room no. 03, Chopda Medicare & Research Centre Pvt. Ltd; Magnum Heart Institute, 3/5, Patil Lane No.1, Laxmi Nagar, Near K.B.H. Vidyalaya, Canada Corner, Nashik-422005
Nashik
MAHARASHTRA 
9656442160

drlaulrs@gmail.com 
Dr Malli Shiv Shantilal  Diva Eye Institute  Consultant Room No-3, First Floor, Diva Eye Institute, 17 Parimal Society ,Core House Lane Near Parimal Garden, Ahmedabad-380006
Ahmadabad
GUJARAT 
9825881773

drshivmalli1986@gmail.com 
Dr Perwez Khan  GSVM Medical college  Department of Ophthalmology, Swaroop Nagar, Kanpur- 208002
Kanpur Nagar
UTTAR PRADESH 
9451875355

perwez.khan@gmail.com 
Dr Santosh Kumar Mahapatra  JPM Rotary Club of Curtack Eye Hospital & Research Institute  JPM Rotary Club of Cuttack Eye Hospital & Research Institute. CDA. Sector-VI, Market Nagar, Cuttack-753014. Odisha India
Cuttack
ORISSA 
9437017762

santosh74mahapatra@gmail.com 
Dr Sandeep Saxena  King George’s Medical University  Department of Ophthalmology, King George’s Medical University, Shahmina road, Chowk, Lucknow-226003, Uttar Pradesh, India.
Lucknow
UTTAR PRADESH 
9415160528

sandeepsaxena2020@yahoo.com 
Dr Smitha K S  KLEs Dr Prabhakar Kore Hospital & MRC  1st Floor Krishna Ward, Room number 17, Department of Ophthalmology, KLEs Dr Prabhakar Kore Hospital & MRC, Nehru Nagar.Belagavi-590010
Belgaum
KARNATAKA 
9964319436

smt_ks@rediffmail.com 
Dr Anup Kelgaonkar  L V Prasad Eye Institute  MTC Campus, Patia, Bhubaneswar PIN – 751024, Odisha
Baleshwar
ORISSA 
8087540324

dranupkelgaonkar@lvpei.org 
Dr Chaitanya Kireetbhai Shukla  Lotus Multispeciality Hospital  Room No.03, 2nd Floor ,N block, Krupa residency, Motera stadium Road, Motera,Sabarmati, Ahmedabad - 380005, Gujarat, India.
Ahmadabad
GUJARAT 
9726132825

drchaitanyashukla@gmail.com 
Dr Dave Vivek Pravin  LV Prasad Eye Institute  LV Prasad Eye Institute, Kallam Anji Reddy Campus, LV Prasad Marg, Banjara Hills, Road No. 2, Hyderabad – 500034, Telengana
Hyderabad
TELANGANA 
7680859900

vivekdave@lvpei.org 
Dr Sameera Nayak  LV Prasad Eye Institute  LV Prasad Eye Institute, Kode Venkatadri Chowdary Campus (KVC), Tadigidapa, Vijayawada, Andhra Pradesh – 521134
Krishna
ANDHRA PRADESH 
9390513748

sameera@lvpei.org 
DrAggarwal Somesh Vedprakash  M & J Institute of Ophthalmology  M & J Institute of Ophthalmology, , Retina Department , First Floor, Manjushri Mill compound , Asarwa, Ahmedabad -16, Gujarat ,India
Ahmadabad
GUJARAT 
9427029044

dr.somesh@yahoo.com 
Dr Naresh Kumar Yadav  Narayana Nethralaya  Narayana Nethralaya, 121/C, Chord Road, 1st Block, Rajaji Nagar, Bangalore, Karnataka – 560010
Bangalore
KARNATAKA 
9980872120

vasudha.naresh@gmail.com 
DrShah Urmil Mahesh  Pagarav Hospital & ICU  Room no.05, Basement,Plot no.512/1, Nr. G-6 Circle, Opp.SBI, Sector -23, Gandhinagar-382023,Gujarat, India.
Gandhinagar
GUJARAT 
9904738885

urmilmshah2010@gmail.com 
Dr Asim Kumar Ghosh  Regional Institute of Ophthalmology  Regional Institute of Ophthalmology, Medical College, Kolkata 88, College Street, Kolkata – 700073, West Bengal
Kolkata
WEST BENGAL 
8240895240

akghosheye@gmail.com 
Dr Divyansh Mishra  Sankara Eye Hospital  Sankara Eye Hospital, Varthur Main Road, Kundalahalli Gate, Bangalore- 560037, Karnataka- India
Bangalore
KARNATAKA 
8977405171

divyansh.mishra@gmail.com 
Dr Abhishek Dixit  Sankat Mochan Nethralaya   Ground floor, Room No. 02, Sankat Mochan Nethralaya and dental care, B 36/4-KH, Saket nagar road, near Sankatmochan, Saket nagar colony, Lanka, Varanasi, Uttar Pradesh 221005
Varanasi
UTTAR PRADESH 
9919106094

dixit.abhishek14@gmail.com 
Dr Manojkumar Rajabhau Saswade  Saswade Netra Rugnalay & Onkar Lasik Laser Centre  Room-02 (Seminar Room) Ground Floor, Saswade Netra Rugnalay & Onkar Lasik Laser Centre, 3, Jay Vishwa Bharti colony, Chetak Ghoda Chowk, Garkheda, Aurangabad, 431005
Aurangabad
MAHARASHTRA 
9422215700

manojsaswade007@gmail.com 
Dr Sandeep Parwal  SMS Hospital  Ground floor, OPD block, Department of Ophthalmology, Charak Bhawan, SMS Hospital, Jaipur-302004, Rajasthan
Jaipur
RAJASTHAN 
8107474333

sparwal321@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 21  
Name of Committee  Approval Status 
Ethics Committee, GSVM Medical College  Approved 
Ethics Committee, SMS Hôspital, Jaipur  Approved 
Ethics Committeee of Ishwar Institute of Health Care  Approved 
Hi-Tech Ethics Committee (HEC)  Approved 
IEC OF B.J .G.M. C AND SASSOON GENERAL HOSPITAL  Approved 
Institutional Ethics Committee, Amrita Institute of Medical Sciences  Approved 
Institutional Ethics Committee, Aravind Eye Hospital, Madhurai  Approved 
Institutional Ethics Committee, JPM Rotary Club of Cuttack Eye Hospital & Research Institute  Approved 
Institutional Ethics Committee, KGMU, Lucknow  Approved 
Institutional Ethics Committee, KLE University  Approved 
Institutional Ethics Committee, L V Prasad Eye Institute, Bhubaneshwar  Approved 
Institutional Ethics Committee, Regional Institute of Ophthalmology, Kolkata  Approved 
Institutional Ethics Committee, Sankara Eye Hôspital  Approved 
Institutional Human Ethics Committee, PSG Institute Of Medical Sciences And Research, Coimbatore  Approved 
L V Prasad Eye Institute Ethics Committee, Hyderabad  Approved 
L V Prasad Eye Institute Ethics Committee, Vijaywada  Approved 
Lotus Ethics Committee  Approved 
Magna-Care Ethics Committee, Nashik  Approved 
Narayana Nethralaya Ethics Committee, Bangalore  Approved 
Opal Institutional Ethics Committee, Sankat Mochan Nethralaya, Varanasi  Approved 
Shrey Hospital Institutional Ethics Committee, Diva Eye Institute,Ahmedabad  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: H318||Other specified disorders of choroid,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Lucentis® Manufactured by Novartis OR Accentrix® Manufactured by Novartis  Ranibizumab will be administered intravitreally in the study eye once per month. 
Intervention  Sun’s Ranibizumab Manufactured by Sun Pharmaceutical Industries Limited  Ranibizumab will be administered intravitreally in the study eye once per month. 
 
Inclusion Criteria  
Age From  50.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1) Ambulatory patients of either gender with ≥ 50 years of age at the time of screening and who are capable of understanding and giving written informed consent.
2) Active primary or recurrent subfoveal lesions with classic or occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye.
(Please note: Only one eye will be considered for study. If both eyes are eligible, the one with the better visual acuity will be selected for treatment unless, based on medical reasons, the investigator deemed the other eye to be more appropriate for treatment. If both eyes have similar visual acuity and similar medical reasons, then right eye will be selected)
3) Best corrected visual acuity, using Early Treatment of Diabetic Retinopathy Study (ETDRS) chart, of 20/40 to 20/320 (Snellen equivalent) in the study eye before pupil dilation.
4) Women of childbearing potential must have a negative urine pregnancy test prior to study entry and agree to use highly effective methods of contraception to prevent pregnancy from study entry till the last dose of the study medication (such contraception may include hormonal birthcontrol e.g., combined estrogen and progestogen containing [oral, intravaginal, or transdermal] or progesterone only [oral, injectable, or implantable] hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone releasing system OR bilateral tubal occlusion, vasectomized partner, or sexual abstinence)
[Note: Women with childbearing potential are defined as: those who are not (1) surgically sterile (bilateral oophorectomy, hysterectomy, or bilateral tubal ligation) or (2) post-menopausal
Post-menopausal woman will be defined as: Women not using hormonal replacement therapy and have had at least 12 continuous months of natural (spontaneous) amenorrhea and be greater than 45 years of age]
 
 
ExclusionCriteria 
Details  A. Prior/Concomitant treatment
1) Prior treatment with verteporfin, external-beam radiation therapy, or transpupillary thermotherapy (TTT), intravitreal drug delivery (steroids or device implantation), anti-VEGF drugs, sub foveal laser photocoagulation, vitrectomy surgery, submacular surgery or other surgical intervene for AMD or any other therapy for AMD in the study eye
2) Intraocular surgery (including cataract surgery) in the study eye within 2 months prior to randomization.
3) Past or Concurrent use of systemic anti-VEGF agents
4) Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs
5) Previous participation in any studies of investigational drugs within 1 month preceding randomization (excluding vitamins and minerals) or planning to participate any other study during the course of this study.
6) Treatment with verteporfin photodynamic therapy in the non-study eye less than 7 days preceding day 1.
7) Laser Photocoagulation (juxtafoveal and extrafoveal) in study eye within 1 month prior to randomization.

B. Ocular conditions in study eye
8) Subfoveal fibrosis or atrophy
9) Sub retinal hemorrhage that involved the center of the fovea, if the size of the hemorrhage was > 50% of the total lesion area
10) Retinal pigment epithelial tear that involved the macula
11) Any concurrent intraocular condition in the study eye (e.g., cataract, diabetic retinopathy, the refractive error more than -8 diopters of myopia etc.) that, in the opinion of the investigator, either
 Required medical or surgical intervention during study period to prevent or treat visual loss that may have resulted from that condition, or
 If allowed to progress untreated, could likely have contributed to loss of at least 2 Snellen equivalent lines of best corrected visual acuity over the study period
12) Patients with current vitreous hemorrhage or history of (1) rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) (2) glaucoma filtering surgery (3) corneal transplant
13) Aphakia or absence of the posterior capsule
14) Active intraocular inflammation (grade trace or above)
15) Uncontrolled glaucoma in the study eye (defined as intraocular pressure [IOP] ≥ 30 mmHg despite treatment with anti-glaucoma medication)
16) Patients with Polypoidal choroidal vasculopathy (PCV) disease at the time of Screening

C. Concurrent ocular conditions in either eyes
17) Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis
18) History of idiopathic or autoimmune-associated uveitis
19) CNV in either eye due to other causes, such as ocular histoplasmosis, trauma or pathologic myopia or CNV lesion not likely to respond to Ranibizumab.

D. Concurrent Systemic Conditions
20) Current signs or symptoms of significant, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, any immunodeficiency and/ or immunosuppressive disease or active systemic infection, cerebral disease that renders the patient incapable of participating in the study.
21) Patients with controlled and uncontrolled Diabetes
E. Other Criteria:
22) Known hypersensitivity to Ranibizumab or any of the components of study medication
23) Allergy to fluorescein dye
24) Presence of uncontrolled systolic blood pressure ≥ 160 mmHg or uncontrolled diastolic blood pressure ≥ 100 mmHg
25) Patients who are HIV, HBsAg, HCV test positive
26) Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality
27) Female subjects who are pregnant, breast- feeding, planning to be pregnant during the study; male patients with partner currently pregnant
28) Employee of the sponsor, investigator, or study center, with direct involvement in the proposed study as well as family members of the employees of sponsor or the investigator.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
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 week 16.  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 week 16. 
 
Secondary Outcome  
Outcome  TimePoints 

1.Mean change in Best Corrected Visual Acuity (BCVA)
2. Proportion of patients who gained at least 15 letters (approximately 3 lines) from baseline Best Corrected Visual acuity (BCVA)
3. Mean Change in central macular thickness assessed by OCT from baseline in the study eye.
4. Number of Participants with Adverse Events throughout the study.
5. Proportion of patients with anti-drug antibodies (ADA) and Neutralizing Antibody (NAb).
 
1. from baseline to end of week 16
2. from baseline to end of week 16
3. from baseline to end of week 16
4. throughout the study
5. at baseline (pre dose Day 1), week 8 and week 16 
 
Target Sample Size   Total Sample Size="160"
Sample Size from India="160" 
Final Enrollment numbers achieved (Total)= "161"
Final Enrollment numbers achieved (India)="161" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   23/10/2020 
Date of Study Completion (India) 29/10/2021 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details
Modification(s)  
Not Applicable 
Individual Participant Data (IPD) Sharing Statement

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

Response - NO
Brief Summary
Modification(s)  

This was a Phase III, randomized, two-arm, multicenter, active-controlled, parallel-group, double-blind, comparative study in patients with wet AMD.

The study was conducted at total 20 geographically distributed centers in India (one site did not screen any patient), having qualified Investigators. The study was initiated only after the receipt of regulatory and EC approval. Total 187 patients were screened to randomize 161 patients from 20 geographically distributed centers in India.

Each clinical trial site was provided with randomization number schedule. After obtaining informed consent, patients were screened by undergoing various assessments and after confirming the eligibility, total 161 patients were randomized in 2:1 ratio to either Sun’s Ranibizumab arm Solution 0.05 mL (0.5 mg) intravitreal injection or Reference Biologic arm (Accentrix®) intravitreal injection in double-blind fashion, as per randomization schedule.

Only one eye per patient was selected as “study eye”. Only study eye received the study drug. Ranibizumab (Test or Reference) 0.5 mg was administered as intravitreal injection on the Day 1, Day 28, Day 56 and Day 84. Reference drug Accentrix®  was used in this study.

Study was amended thrice.

Version No. 1.2; dated 29/SEP/2020: CTCAE as criteria for safety was considered for this study

Version 2.0 dated 12/FEB/2021: Exclusion criteria no. 21 modified to ‘Patients with HbA1c > 7’ was considered a relevant population for Ranibizumab in wet-AMD indication. Moreover, these subjects were not excluded in innovator Pivotal clinical trials conducted for approval in this indication.

Version No. 2.1; dated 30/APR/2021: Added diabetic retinopathy as a separate exclusion criteria no. 11 as per SEC recommendations and deleted diabetic retinopathy in exclusion criteria no. 12 as per SEC recommendations

Total duration of the trial was 126 (14 days screening + 112 days treatment period) comprising of total 7 visits: The study was planned as follows:

Screening: 14 days (Day -14 to Day -1)

Visit 2: Randomization/Day 1

Visit 3: Day 7 ±2

Visit 4: Day 28 ±2

Visit 5: Day 56 ±2

Visit 6: Day 84 ±2, End of Treatment (EOT)

Visit 7: Day 112 ±2, End of Study (EOS)/Early Termination (ET)

The efficacy, safety and immunogenicity were assessed during the study period. Patients who are withdrawn/ terminating early from the study completed EOS visit assessment. Day 84 were End of treatment day.

After completion of Study, based on the OCT result and Investigator’s judgement patient were further shifted on Pro Re Nata (PRN) Regimen or Treat and Extend (T&E) Regimen. After completion of study, the patient responding to treatment were provided with drug beyond the clinical trial till such duration as recommended by the Principal Investigator or as per rules of post-trial access of investigational product.

Study results conclusion:

Based on results of primary endpoint, Sun’s ranibizumab biosimilar can be considered therapeutically equivalent to reference biologic product, Accentrix®. Sun’s ranibizumab was comparable to reference product for all secondary endpoints as well. Overall, both the products were safe. There were no additional safety or immunogenicity concerns emerged during the study.


 
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