Health Condition 1: H00-H59- Diseases of the eye and adnexa
Conditions
Interventions
Intervention1: Bevacizumab arm (T): Dose: Single-use vial, Unit Dose Strength: Each single-use vial contains 5.75 mg of
bevacizumab in 0.23 mL solution, Dosage Level: 1.25 mg (0.05 mL of 25 mg/mL)
int
Sponsors
Intas Pharmaceuticals Ltd.
Intas Pharmaceuticals Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1) Must sign an ICF indicating that the participant understands the purpose of, and procedures required for the study as described in section 10.1.3 and in this protocol and is willing to abide by the requirements during participation in the study. 2) Male or and female (assigned at birth, inclusive of all gender identities) 3) Age of greater than or equal to 50 (completed years) at the time of signing the informed consent. 4) Primary or recurrent, Anti-VEGF na ve participants with active choroid neovascularization (CNV) lesion involving the central subfield secondary to neovascular (wet) age-related macular degeneration (AMD) in the study eye at Screening as assessed by the investigator. Note 1: Active CNV indicates the presence of leakage as evidenced by Fluorescein Angiography (FA) and or intra- or subretinal fluid as evidenced by Optical Coherence Tomography (OCT). Note 2: All subtypes of nAMD CNV lesions are permissible (i.e., classic CNV, occult CNV, or with some classic CNV component, or retinal angiomatous proliferation lesions with a CNV component). Note 3: If both eyes are affected and eligible, the investigator should consider the worst eye in preference to the other, if the fellow eye can await treatment with anti-VEGF for the duration of study participation. 5) BCVA of less than or equal to 73 and greater than or equal to 24 ETDRS letter score (Approximate 20 per 40 and 20 per 320 Snellens equivalent) using Early Treatment Diabetic Retinopathy Study chart (ETDRS) testing at a distance of 4 meters in the study eye at Screening and Baseline. 6) Study eye with sufficiently clear ocular media and adequate pupillary dilation that allows for adequate visualization of the fundus with indirect ophthalmoscopy and to permit adequate quality ocular imaging. 7) A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1 precent per year), with low user dependency when used consistently and correctly, as described in section 10.4 during the intervention period and for at least 3 months after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. WOCBP agrees not to donate eggs (ova, oocytes), freeze them for future use for reproduction or retrieve them for their own use during the recommended period of contraception. A WOCBP must have a negative highly sensitive serum B-human chorionic gonadotropin (BhCG) test at Screening and urine BhCG test at Baseline. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnant 8) Male participants are eligible to participate if they agree to the following during the intervention period and for at least 03 months after the last dose of the study intervention. Must agree not
Exclusion criteria
Exclusion criteria: 1) Poor quality of SD-OCT and fundus angiography images at Screening Baseline. 2) Presence of fibrosis, atrophy or scarring involving fovea in the study eye at Screening as assessed qualitatively by the investigator from CFP FA images. 3) Subretinal haemorrhage in the central subfield of the study eye which either (a) involves fovea; or (b) has a total area of greater than or equal to 50 percent of the total lesion area at Screening as assessed qualitatively based on the visual inspection of the CFP by the investigator. Total lesion area is defined as contiguous area of abnormal tissue that will include blood, scars, neovascularization, fibrosis and atrophy. 4) Any infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis in either eye within 4 weeks prior to Baseline. 5) Any active intraocular inflammation (grade trace or above) in the study eye within 4 weeks prior to Baseline. 6) History of idiopathic or autoimmune-associated uveitis in either eye. 7) CNV in the study eyes due to causes other than AMD such as DME, RVO, histoplasmosis, trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture or pathologic myopia (spherical equivalent of -6 dioptres or more negative) or CNV lesion not likely to respond to anti-VEGF. 8) Participants 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. 9) Prior interventions in the study eye Prior Treatment with verteporfin, laser photocoagulation, external beam radiation treatment and Transpupillary thermotherapy (a) within 5 years prior to randomization if it involves the fovea in the study eye; OR (b) within 3 months prior to randomization if anywhere beyond fovea in the study eye. Prior vitrectomy in the study eye. Prior glaucoma filtration surgery in the study eye. Prior corneal transplant in the study eye. Sub-macular surgery or any surgical intervention for AMD in study eye. Prior ocular surgery (including cataract) within the previous 2 months from baseline in the study eye. 10) Prior treatment with Any prior anti-VEGF, including but not limited to Ranibizumab, bevacizumab, aflibercept and pegaptanib (intravitreal or systemic) in either eye. Previous treatment with intravitreal steroids (e.g., triamcinolone, anecortave acetate) in the study eye within 3 months prior to randomization or intravitreal steroid implant (like Ozurdex) within 6 months prior to randomization. 11) Known allergies, hypersensitivity, or intolerance to any of the study interventions, or components excipients thereof [Refer Investigators Brochure (IB) of bevacizumab[5] and Indian Prescribing Information (PI) of Ranibizumab [6]/Summary of Product Characteristics (SmPC) of Ranibizumab[7] ], or to drugs of similar chemical class or to fluorescein or any other component of fluorescein formulation or to topical anaesthetics or mydriatic medications. The participant 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. 12) Current or planned use of systemic medications known to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine hydroxychloroquine, tamoxifen, phenothiazines and ethambutol. 13)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 2: To assess and compare safety of Intas bevacizumab with Ranibizumab in participants with wet neovascular AMD. Phase 3: To assess the noninferiority of Intas bevacizumab to Ranibizumab in participants with wet neovascular AMD.Timepoint: Pre-dose before first dose (Day 1) and third dose (Day 57), Pre-dose before second dose (Day 29), After first dose (Day 1), 8.000, 12.000, 16.000, 20.000, 24.000 28.000 hrs, After third dose (Day 57) 8.000, 12.000, 16.000, 20.000, 24.000 28.000 hrs, Day 85. | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 2: To assess and compare efficacy parameters of Intas bevacizumab with Ranibizumab in participants with wet neovascular AMD. Phase 3: To assess and compare additional efficacy parameters of Intas bevacizumab with Ranibizumab in participants with wet neovascular AMD.Timepoint: Pre-dose before first dose (Day 1) and third dose (Day 57), Pre-dose before second dose (Day 29), After first dose (Day 1), 8.000, 12.000, 16.000, 20.000, 24.000 28.000 hrs, After third dose (Day 57) 8.000, 12.000, 16.000, 20.000, 24.000 28.000 hrs, Day 85.;Phase 2: 1) To assess immunogenicity of Intas bevacizumab with Ranibizumab in participants with wet neovascular AMD. 2) To estimate the systemic levels of Intas bevacizumab with Ranibizumab. Phase 3: 1) To assess and compare safety of Intas bevacizumab with Ranibizumab in participants with wet neovascular AMD. 2) To assess immunogenicity of Intas bevacizumab with Ranibizumab in participants with wet neovascular AMD.Timepoint: Pre-dose before first dose (Day 1, 3 samples) and third dose (Day 57), Day 15, Pre-dose before second dose (Day 29), Day 85. | — |
Countries
India
Contacts
Public ContactDr Jogesh Mahajan
Lambda Therapeutic Research Ltd
Outcome results
None listed