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IRCT20150303021315N9 IRCT 2018-01-18 AryoGen Pharmed Co. The comparison of the efficacy and safety between Temziva and Actemra in treatment of the patient with active Rheumatoid Arthritis A phase 3, randomized, multicenter, double-blind, two-armed, parallel, active-controlled, equivalency clinical trial to compare efficacy and safety of Temziva (Tocilizumab produced by AryoGen Pharmed) versus Actemra® (Tocilizumab produced by Genentech-Roche co.) in patients with active moderate to severe rheumatoid arthritis 2022-11-01 anticipated 272 Complete https://irct.ir/trial/18717 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 4.0.2 Blocks (with the size 2 or 4) will be made using permuted block randomization for a total of 272 patients (1:1 allocation ratio). After randomization procedure, a code will be allocated to each patient that will be used as the 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 code described is followed by study unique identification code consisting of first two letters of the generic name of the investigational product and study phase number respectively (which is TOC) and three numbers (corresponding to the randomization number), e.g. ABCD001TOC-001. The randomization number will be assigned in a consecutive way, Blinding description: Both products used in the study will be entirely indistinguishable for patients and ‎health care providers since they are identical in shape, size, material and color. They don't differ in appearance. The compartments of both Tocilizumab drugs are packaged in same pack. such a way that they do not differ in appearance. Also, a suitable label is designed for pre-filled boxes and syringes. The contents of the labels are based on EMA regulation. The brand's medicine and produced medicine in the factory are completely relabeled and packaged in the same way. The blinding codes are listed on the drug label, and each drug is linked to the patient through the specific code. The patient, medical staff, and other staff are not disclosed to the type of medication that being taken. The group of patients and the type of medication they receive are not disclosed to the researchers and are kept in opaque sealed envelopes with the researcher at each center. In addition, people who review the results and analyze the data are unaware of the type of grouping of patients and they cannot distinguish the type of brand of a drug by its appearance. 3 Rheumatoid Arthritis. Intervention 1: Temziva (produced by AryoGen Pharmed) prefilled syringe for patients with dose of 162 mg, subcutaneous (S/C) injection every other week during 24 weeks of study. Intervention 2: Actemra® (produced by Genentech-Roche Company)prefilled syringe for patients with dose of 162 mg, subcutaneous (S/C) injection every other week during 24 weeks of study. No - There is not a plan to make this available Justification or reason for not sharing IPD is There is no plan for this purpose
public Dr. Nassim Anjidani
No 42, Attar St., Vanak Sq.
Tehran Iran (Islamic Republic of) 1994766411 +98 21 4347 3000 anjidani.n@orchidpharmed.com OrchidPahrmed Co scientific Dr. Ahmadreza Jamshidi
Rheumatology research Center, Dr. Shariati Hospital, North Kargar St, Tehran, Iran.
Tehran Iran (Islamic Republic of) 1411713137 +98 21 8822 0065 Jamshida@sina.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) Male or female aged 18 –65 years at the time of signing the informed consent form Participants who have been diagnosed as having rheumatoid arthritis for at least 6 months, using the 2010 American College of Rheumatology/European League Against Rheumatism (2010 ACR/EULAR) classification criteria for RA. Patients who have an inadequate response of at least 12 weeks to ≥ 1 conventional disease-modifying antirheumatic drugs (DMARDs) in which 1 of them is definitely methotrexate, according to their investigator judgment. Moderate to severe rheumatoid arthritis with ≥4 tender joints (of 68 joints); ≥4 swollen joints (of 66 joints); and an erythrocyte sedimentation rate (ESR) ≥30 mm/hour or a C-reactive protein level (CRP) ≥1.0 mg/dl at screening Patients discontinued all biological DMARD, including etanercept for 2 weeks or longer and infliximab, certolizumab, golimumab or adalimumab for 8 weeks or longer because of side effects, lack of compliance or lack of response. Ability to comprehend and willingness to sign the Informed Consent Form for this study 18 years 65 years Both Active tuberculosis or Patients testing positive for latent tuberculosis (PPD > abnormal CXR) Have a history of serious allergies or a known hypersensitivity to Tocilizumab or any components of the formulations. Have an active hepatitis B or C or positive hepatitis B surface antigen or hepatitis C antibody. Have a known history of infection with human immunodeficiency virus (HIV). Patients who are weighing ≥ 100 kg Patients who had thrombocytopenia (platelet count < 100,000/µl) or Leucopenia (ANC<2,000/µl or white blood cell count < 3,500/µl). Patients with aspartate transaminase (AST), alanine transaminase (ALT) 1.5-fold the upper limit of maximum-normal. Patients with Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis. (Class IV: Advanced persistent limitation inability to perform usual self-care, vocational, and avocational activities). Patients who have been received previous treatment with Tocilizumab Patients who had received plasmapheresis or major surgery (including joint surgery, major cardiovascular surgery except for revascularization) within 8 weeks before entering study or planned major surgery within 6 months after entering the study. Patients who had previously received Rituximab within one year before starting the study. Patients who had received oral glucocorticoids at a dosage of > 10 mg/day of prednisolone or equivalent; or had a dose increase, new administration, or intravenous, intraarticular or intramuscular injections of glucocorticoids within 4 weeks of Tocilizumab treatment. Patients who had dose changes or added-in DMARDs or immunosuppressants within 4 weeks of Tocilizumab treatment. Immunization with a live/attenuated vaccine less than 4 weeks before baseline or planning to receive a live vaccine during the study. Women who are pregnant, breastfeeding or planning to become pregnant during the study. Patients who have stopped previous MTX treatment due to hepatotoxicity. Patients with an active infection or who have had a serious infection or have been treated with intravenous antibiotics for an infection within 8 weeks or oral antibiotics within 2 weeks prior to screening. Having history of any malignancy within the previous 5 years prior to Screening. Having rheumatic disease or inflammatory joint disease other than rheumatoid arthritis Having history of demyelinating disorders including multiple sclerosis. Patients with a certain history of gastrointestinal disorders such as diverticulitis, active peptic ulcer or active duodenal ulcer which have been approved by a gastroenterologist. Patients who had GFR< 60 ml/min/1.73 m2 Patients with a history of treatment with cyclosporine or tacrolimus within 1 month of receiving tocilizumab. Having any other disease or disorder which, in the opinion of the Investigator, will put the subject at risk if they are enrolled. Patients who had previously received JAK inhibitors. M05.8, M06 Other seropositive rheumatoid arthritis ,Seronegative rheumatoid arthritis Treatment - Drugs Treatment - Drugs Temziva (produced by AryoGen Pharmed) prefilled syringe for patients with dose of 162 mg, subcutaneous (S/C) injection every other week during 24 weeks of study Actemra® (produced by Genentech-Roche Company)prefilled syringe for patients with dose of 162 mg, subcutaneous (S/C) injection every other week during 24 weeks of study. The patients response. Timepoint: Prior to, and 24 weeks after first intervention. Method of measurement: ACR 20 response criteria. The patients response. Timepoint: Prior to intervention and 12 weeks after the first intervention. Method of measurement: ACR20 response criteria. The patients response. Timepoint: 12 and 24 weeks after the first intervention. Method of measurement: ACR50 and ACR70 response criteria. Change in patients disability. Timepoint: Prior to intervention, 12 and 24 weeks after the first intervention. Method of measurement: HAQ Questionnaire. Change in Disease Activity. Timepoint: 12 and 24 weeks after the first intervention. Method of measurement: DAS-28 index. Percentage of the patients at remission. Timepoint: 12 and 24 weeks after the first intervention. Method of measurement: DAS-28 index score below 2.6. Adverse events (AEs), Adverse drug reactions (ADR). Timepoint: at screening visit and at each visit including day 0 and weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 after the first injection. Method of measurement: Medical examination. Changes in physical examination findings. Timepoint: at screening visit, and 12 and 24 weeks after the first intervention. Method of measurement: Medical examination. Changes in vital signs (blood pressure). Timepoint: at screening visit and prior to intervention, and weeks 12 and 24 after the first intervention. Method of measurement: Medical examination. Immunogenicity of the drug. Timepoint: Prior to intervention, and 12 and 24 weeks after the first intervention. Method of measurement: laboratory tests. AryoGen Pharmed Co. Approved 2017-11-07 Ethics committee of Shahid Beheshti University of Medical Sciences 3th floor, school of medicine, Evin, Chamran Highway, Tehran, Iran Tehran Tehran Iran (Islamic Republic of) Approved 2018-01-13 Ethics committee of Tehran University of Medical Sciences Tehran University of Medical Sciences, Ghods street, Keshavarz boulevard Tehran Tehran Iran (Islamic Republic of)