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
The Ethics Committee of the Eye Foundation, Coimbatore
The Institutional Ethics Committee B J Medical College and Civil Hospital Ahmedabad
Yash Societys Sujata Birla Hospital Ethics Committee
Regulatory Clearance Status from DCGI
Health Condition / Problems Studied
Degeneration of macula and posterior pole
Intervention / Comparator Agent
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).
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).
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.
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.
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
Participant and Investigator Blinded
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.
This is a randomized, comparative, parallel group, two arm, double blind, multi-centerPhase 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.
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
CTRI/2019/09/021456 [Registered on: 30/09/2019] Trial Registered Prospectively
Last Modified On:
Post Graduate Thesis
Type of Trial
Type of Study
Other (Specify) [Biosimilar ]
Randomized, Parallel Group, Active Controlled Trial
1. Willingness and ability to undertake all scheduled visits and assessments as judged by the investigator
2. Age ≥50 years at Screening
3. Males, or females of nonchildbearing potential (eg, permanently sterilized, postmenopausal [defined as 12 months with no menses without an alternative medical cause prior to Screening])
4. Newly diagnosed, treatment-naive, active subfoveal CNV lesion secondary to AMD in the study eye. Active CNV means presence of leakage as evidenced by fluorescein angiography (FA) and intra- or sub-retinal fluid as evidenced by optical coherence tomography (OCT) that is confirmed by central reading center during Screening (before randomization)
5. Total lesion area ≤9.0 disc areas in size (including blood, scars, and neovascularization) as assessed by FA in the study eye and confirmed by the central reading center before randomization
6. The area of CNV must be ≥50% of the total lesion area in the study eye confirmed by the central reading center before randomization
7. Best corrected visual acuity of 20/40 to 20/200 in the study eye using ETDRS chart (≤ 73 and ≥ 34 ETDRS letters) at Screening and at Day 1 before randomization.
8. Fellow eye should not be expected to need any anti-vascular endothelial growth factor (VEGF) treatment for the duration of study participation
9. Written informed consent form (ICF) obtained before any study-related procedures or performed.
10. Male subjects must be willing to completely abstain or agree to use an appropriate method of contraception from the time of signing ICF and for the duration of study participation through 3 months after the last dose of study drug.
1. Previous ocular treatment/surgery for wAMD in either eye
2. Previous intravitreal treatment/vitreal surgery in either eye
3. Any previous intravitreal anti-VEGF treatment (eg, bevacizumab, aflibercept, ranibizumab) in either eye
4. Any previous systemic anti-VEGF treatment
5. Sub- or intraretinal hemorrhage involving the fovea in the study eye of 50% or more of the total lesion area assessed by FA and confirmed by central reading center (Before Randomization)
6. Subfoveal fibrosis or atrophy in the study eye assessed by FA and confirmed by central reading center (before randomization)
7. Scarring exceeding 50% of total lesion size in the study eye and confirmed by the central reading center (before randomization)
8. Choroidal neovascularization in either eye due to nonAMD causes assessed by FA and confirmed by central reading center (before randomization)
9. Retinal pigment epithelial tear involving the macula in the study eye as assessed by FA and confirmed by central reading center (before randomization)
10. Any concurrent intraocular condition in the study eye (eg, cataract or diabetic retinopathy) that, in the opinion of the investigator, could require treatment during the study period to prevent or treat loss of visual acuity
11. Other intraocular surgery (including cataract surgery) or periocular surgery in the study eye within 3 months prior to randomization, except for eyelid surgery within 30 days prior to randomization
12. Corneal transplant in the study eye
13. Active or recent (within 28 days prior to randomization) intraocular, extraocular and periocular inflammation or infection in either eye, including infectious conjunctivitis, keratitis, scleritis, or endophthalmitis
14. Current vitreous hemorrhage in the study eye
15. History of retinal detachment in the study eye
16. History of macular hole in the study eye
17. History of idiopathic or autoimmune-associated uveitis in either eye
18. Aphakia or absence of the posterior capsule in the study eye, unless it occurred as a result of a Yttrium Aluminium Garnet posterior capsulotomy in association with prior posterior chamber intraocular lens implantation
19. Presence of advanced glaucoma or optic neuropathy that involves or threaten the central visual field in the study eye
20. History of glaucoma filtering surgery in the study eye
21. Uncontrolled ocular hypertension in the study eye, defined as intraocular pressure ≥ 25 mm Hg despite treatment with anti-glaucoma medication
22. Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia
23. Contraindication for Lucentis® (hypersensitivity to ranibizumab or to any of the excipients, active or suspected ocular or periocular infection, or active severe intraocular inflammation), or known allergic reactions to any ingredients of QL1205
24. Current treatment for active systemic infection
25. Subjects with known history ofseropositivity for hepatitis B, hepatitis C antibody, HIV antibody, syphilis tests, or any immunodeficiency and/or immunosuppressive disease or active systemic infection. Seropositivity for hepatitis B is defined as (1) positive for hepatitis B surface antigen, and (2) positive for hepatitis B virus DNA
26. Reasonable suspicion of a disease or condition that that might render the subject at high risk of treatment complications or affect interpretation of the study results (as judged by the investigator), such as uncontrolled hypertension (systolic blood pressure > 160 mm Hg or diastolic blood pressure
27. Participation in another clinical trial within the previous 3 months or any previous participation in a clinical trial of anti-angiogenic drugs with receipt of previous study drug within 3 months the ICF for this study
28. Topical ocular corticosteroids administrated for ≥ 30 consecutive days in the study eye within 90 days prior to randomization
29. Any systemic treatment or therapy (including prescribed herbal medication) to treat neovascular AMD within 30 days prior to randomization, and such treatment or therapy will not be allowed during the study period. However, dietary supplements, vitamins, or mineral will be allowed
30. PK subgroup only: contraindication for additional blood sampling (as judged by the investigator)
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
This is a Phase 3, multicenter, randomized, double-masked (double-blinded), randomized, parallel-group study in subjects with wAMD. Subjects will be randomized 1:1 to receive Lucentis® or QL1205.
Subjects in a PK subgroup will provide blood samples for measurement of serum ranibizumab immediately before the first dose of investigational product (QL1205) or reference product (Lucentis®) and 22 hours after the first dose (Day1) and the sixth dose (Week 20) at expected time to maximum serum concentration (0.9 days).