]>
IRCT20150303021315N14 IRCT 2019-06-30 CinnaGen company The Effect of Aflibercept on Treatment of Age-related macular Degeneration A Phase III, multicenter, randomized, two-armed, double-blind, ‎parallel, active-controlled, non-inferiority clinical trial to compare efficacy ‎and safety of test-Aflibercept (CinnaGen Co, Iran) to the reference ‎Aflibercept product (Eylea®, Regeneron, USA) in patients with ‎Neovascular age-related macular degeneration.‎ 2019-07-23 anticipated 168 Complete https://irct.ir/trial/39479 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Randomization description: The randomization plan of the patients will be carried out centrally using an R-CRAN software ‎version 3.2.3. Blocks (with the size 2 or 4) will be made using permuted block randomization for ‎a total of 168 patients (1:1 allocation ratio). After the randomization procedure, a code will be ‎allocated to each patient that will be used as a patient identifier throughout the study. The assigned ‎code will be denoted by 4 initials (corresponding to the first two letters of the first name, first two ‎letters of surname) and 3 numbers (center code). Moreover, the described code is followed by ‎study unique identification code consisting of first three letters of the generic name of the ‎investigational product (AFL), and three numbers (corresponding to the randomization number), ‎e.g. ABCD001AFL-001. The randomization number will be assigned in a consecutive way.‎, Blinding description: Both Aflibercept products used in the study will be entirely indistinguishable for patients and ‎health care providers since they are identical in shape, size, label, and color. The container of the ‎drugs will be labeled using identical Labels so they will be impossible to differentiation. Patients ‎groups and their drugs will not be disclosed to investigators. After that, the patient signed ‎Informed consent and considered to be eligible base on‏ ‏the inclusion and exclusion criteria; he or ‎she will be allocated to one of each group. ‎‏ ‏The investigator will not be informed of randomization, ‎and all the drug codes will be placed in an opaque pocket inside each sites trial Master file. Data ‎analyzers will not be informed of the patients' grouping.‎. 3 Neovascular age-related macular Degeneration. Intervention 1: Aflibercept (CinnaGen Co, Iran) 2 mg (0.05 mL) by intravitreal injection every 4 weeks (Monthly) for the first 3 ‎injections, followed by 2 mg every 8 weeks (every two months) Until week 48 of study. Intervention 2: Eylea (Regeneron, USA) 2 mg (0.05 mL) by intravitreal injection every 4 weeks (Monthly) for the first 3 injections, ‎followed by 2 mg every 8 weeks (every two months) Until week 48 of study.‎. Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is It is not yet known if there will be a plan to make this available
public Dr. Nasim Anjidani
No 42, Atar S.q, Atar St., Vanak S.q, Valiasr St., Tehran, Iran
Tehran Iran (Islamic Republic of) 19947766411 +98 21 8808 8821 anjidani.n@orchidpharmed.com Orchid Pharmed Co. scientific Dr. Reza Karkhane
Farabi Hospital, Kargar Jonoobi St., District 11
Tehran Iran (Islamic Republic of) 1336616351 +98 21 5540 0003 Karkhane@tums.ac.ir Tehran University of Medical Sciences Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) male or female aged 55-80 years at the time of signing the informed consent form.‎ Patients with Primary active CNV subfoveal lesion secondary to AMD (with definite diagnosis of AMD ‎according to physician’s decision based on the results of ocular examination, or OCT)‎ the ETDRS-best-corrected visual acuity index with the score of 20/40 to 20/320 (or BCVA letter score of ‎‎73 to 25 in the study eye)‎ Willing, committed, and able to return for clinic visits and complete all study-related procedures Patients with the ability to read, understand and willing to sign the informed consent form for participation ‎in the study 55 years 80 years Both Any prior ocular (in the study eye) or systemic anti-VEGF therapy, during the past 3 months, Photodynamic ‎Therapy (PDT) or surgery for neovascular AMD.‎ The need for receiving ocular anti-VEGF simultaneously in both eyes in the loading phase for the treatment of ‎neovascular AMD Scar, fibrosis, or extensive subretinal hemorrhage of more than 50% of the total lesion area in the study eye, ‎according to the physician's opinion based on clinical presentation or according to fundus photography.‎ The presence of scar, fibrosis, or atrophy in the central part of the fovea in the study eye‎ The presence of retinal pigment epithelial tears or rips involving the macular part of the study eye at the time of ‎entering the study The history of any vitreous hemorrhage within 4 weeks prior to the first visit of the study in the study eye‎ Presence of other causes of CNV in the study eye‎ Clinical or paraclinical diagnosis of PCV by physician’s diagnosis‎ The history or clinical evidence of diabetic retinopathy, diabetic macular edema, or any other vascular disease ‎affecting the retina, other than AMD in either eyes‎ Prior vitrectomy in the study eye‎ History of retinal detachment or treatment or surgery for retinal detachment in the study eye‎ Any history of a macular hole of stage 2 or above in the study eye‎ Any intraocular or periocular surgery within three months of the screening visit on the study eye except lid surgery, ‎which may not have taken place within one month of screening visit‎ Prior trabeculectomy or any other filtration surgery in the study eye‎ Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma ‎medication) in the study eye‎ Active intraocular inflammation in either eye‎ Active ocular or periocular infection in either eye or any ocular or periocular infection within the last two weeks prior ‎to screening visit in either eye‎ Any history of uveitis in either eye‎ Presence or history of scleromalacia in either eye‎ Aphakia or pseudophakia with the absence of posterior capsule (unless it occurred as a result of a yttrium ‎aluminum garnet [YAG] posterior capsulotomy) in the study eye Previous therapeutic radiation in the region of the study eye‎ History of corneal transplant or corneal dystrophy in the study eye‎ Any significant media opacities, including cataract, in the study eye that might interfere with visual acuity, ‎assessment of drug safety, or fundus photography‎ Patients with amblyopia. Patients with blindness in the fellow eye Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could require either ‎medical or surgical intervention during the study period Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the ‎risk to the patient beyond what is to be expected from standard procedures of intraocular injection, or which ‎otherwise may interfere with the injection procedure or with evaluation of efficacy or safety‎ History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving ‎reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might ‎affect the interpretation of the results of the study or render the patient at high risk for treatment complications‎ Participation as a patient in any clinical study within the 12 weeks prior to the screening visit‎ The use of long-acting steroids, either systemically or intraocularly, in the six months prior to screening visit‎ Any history of allergy to povidone iodine‎ Females who are pregnant, breastfeeding, planning to become pregnant during the study period, unwilling to ‎practice adequate contraception throughout the study and for at least 60 days following the last dose of study ‎medication ‏History of stroke, myocardial infarction or uncontrolled hypertension (blood pressure >160/100 despite receiving ‎medical treatment) for less than three months from the date of the Screening visit‎ Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, ‎pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders‎ H35.32 Exudative age-related macular degeneration Treatment - Drugs Treatment - Drugs Aflibercept (CinnaGen Co, Iran) 2 mg (0.05 mL) by intravitreal injection every 4 weeks (Monthly) for the first 3 ‎injections, followed by 2 mg every 8 weeks (every two months) Until week 48 of study Eylea (Regeneron, USA) 2 mg (0.05 mL) by intravitreal injection every 4 weeks (Monthly) for the first 3 injections, ‎followed by 2 mg every 8 weeks (every two months) Until week 48 of study.‎ The proportion of patients achieving maintaining vision (losing<15‎‏ ‏letter on ETDRS chart) at week 52, in ‎comparison to visit 0.‎. Timepoint: baseline visit, 52 weeks after first intervention. Method of measurement: Tumbling-E ETDRS chart. Mean changes in the Best-Corrected Visual Acuity Index measured with ETDRS chart from visit baseline to week 52‎. Timepoint: baseline visit and 52 weeks after first intervention. Method of measurement: Tumbling E ETDRS chart. The percentage of patients who have increase of ≥15‎‏ ‏score in ETDRS at week 52. Timepoint: baseline visit and 52 weeks after first intervention. Method of measurement: Tumbling E ETDRS chart. The mean change in National Eye Institute Visual Function Questionnaire (NEI VFQ-25) at week 52 compared to ‎the visit baseline. Timepoint: Baseline Visit and 52 weeks after first intervention. Method of measurement: NEI VFQ-25. Mean changes in central retinal thickness based on structural OCT at week 52 compared to the screening visit‎. Timepoint: screening visit‎ and 52 weeks after first intervention. Method of measurement: Optical Coherence Tumography (OCT). The percentage of patients without intra-retinal fluid and subretinal fluid based on structural OCT at week 52‎. Timepoint: 52 weeks after first intervention. Method of measurement: Optical Coherence tumography. Systemic and Ophthalmic Adverse events (AEs) and adverse drug reactions (ADR)‎‏ ‏‎– at ‎screening, visit 1 and all the follow-up visits until week 52‎. Timepoint: All of the study visits. Method of measurement: Physical examination. Comparing immunogenicity of two products and evaluating antibody formation- at ‎screening visit, week 24 and week 52.‎. Timepoint: screening visit, 24 weeks, and 52 weeks after first intervention. Method of measurement: ELISA Assay. Evaluation of blood pressure- at screening visit and week 52‎. Timepoint: Screening Visit, 52 weeks after first intervention. Method of measurement: blood pressure meter. Clinical laboratory testing for systemic safety, including liver and kidney functions, ‎complete blood count and clinical bio-chemistries- at regular intervals‎. Timepoint: screening visit, 24 weeks and 52 weeks after first intervention. Method of measurement: Lab test. Changes in physical examination findings- at screening visit and week 52‎. Timepoint: Screening Visit, and 52 weeks after first intervention. Method of measurement: Physical examination. CinnaGen company Approved 2019-05-07 The Ethics Committee of Tehran University of Medical Sciences Qods St., Keshavarz Blvd Tehran Tehran Iran (Islamic Republic of)