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IRCT20150303021315N13 IRCT 2019-06-10 CinnaGen company Evaluating the efficacy and safety of Ocrelizumab (CinnaGen, Iran) in comparison to Ocrevus® (Roche, Switzerland) in patients with relapsing multiple sclerosis A Phase III, randomized, two-armed, double-blind, ‎parallel,active-controlled, clinical trial to evaluate equivalency of the efficacy and safety of Ocrelizumab (CinnaGen, Iran) in comparison to reference product, Ocrevus® (Roche, Switzerland) in patients with relapsing multiple sclerosis 2019-06-22 anticipated 170 Complete https://irct.ir/trial/39481 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Randomization description: Eligible patients will be assigned to treatment with the use of a dynamic randomization algorithm that will be designed to achieve overall balance between groups. Randomization will be stratified according to The Expanded Disability Status Scale (EDSS) (≤ 4 vs > 4). After randomization procedure, a code will be allocated to each patient that will be used as patient identifier throughout the study. The assigned code will be denoted by 4 initials (corresponding to the first two letters of 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, i.e. OCR and four numbers (corresponding to the randomization number), e.g. ABCD001OCR-001, Blinding description: Both Ocrelizumab 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' group. 3 Relapsing Multiple Sclerosis (RMS). Intervention 1: Intervention group: Ocrelizumab (CinnaGen, Iran) 600 mg (given as dual infusions of ocrelizumab 300 mg on Days 1 and 15 of the first 24-week treatment cycle and as single infusions of 600 mg on Day 1 for each 24-week treatment cycle, thereafter) every 24 weeks, intravenously at weeks 0, 2, 24, 48 and 72. Intervention 2: Intervention group: Ocrelizumab (Roche, Switzerland) 600 mg (given as dual infusions of ocrelizumab 300 mg on Days 1 and 15 of the first 24-week treatment cycle and as single infusions of 600 mg on Day 1 for each 24-week treatment cycle, thereafter) every 24 weeks, intravenously at weeks 0, 2, 24, 48 and 72. 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, Attar St., Vanak Sq, Tehran, Iran
Tehran Iran (Islamic Republic of) 1994766411 +98 21 4347 3000 anjidani.n@orchidpharmed.com Orchid Pharmed Co. scientific Dr Mohammad Ali Sahraian
MS Research Center, Sina Hospital, Hasan Abad Square- Emam Khomeyni Street, Tehran
Tehran Iran (Islamic Republic of) 1136746911 +98 21 6634 8571 sahraian1350@yahoo.com 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) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Ability to provide written, informed consent and to be compliant with the schedule of protocol assessments. Ages 18-55 years at screening, inclusive. Diagnosis of MS, in accordance with the revised McDonald criteria (2010). At least two relapses having occurred within the past 2 years or one relapse within the past 12 months prior to screening. Neurological stability for ≥ 30 days prior to both screening and baseline. EDSS, at screening, from 0 to 5.5 inclusive. Patients of reproductive potential must use reliable means of contraception. 18 years 55 years Both Diagnosis of primary progressive or relapsing progressive MS. Disease duration of more than 10 years in patients with an EDSS ≤ 2.0 at screening. Inability to complete an MRI (contraindications for MRI include but are not restricted to claustrophobia, weight ≥ 140 kg, pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc). Known presence of other neurological disorders which may mimic MS including but not limited to: neuromeylitis optica, untreated vitamin B12 deficiency, neurosarcoidosis and cerebrovascular disorders. Pregnancy or lactation. Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study. History or currently active primary or secondary immunodeficiency. Lack of peripheral venous access. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Significant or uncontrolled somatic disease or any other significant disease that may preclude patient from participating in the study.Congestive heart failure (NYHA III or IV functional severity). Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds. Infection requiring hospitalization or treatment with I.V. antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit. History or known presence of recurrent or chronic infection (e.g., hepatitis B or C, HIV, syphilis, tuberculosis). History of progressive multifocal leukoencephalopathy (PML). History of malignancy, including solid tumors and hematological malignancies, except basal cell carcinoma, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix of the uterus that have been previously completely excised with documented, clear margins. History of alcohol or drug abuse within 24 weeks prior to baseline History or laboratory evidence of coagulation disorders. Receipt of a live vaccine within 6 weeks prior to baseline. In rare cases when patient requires vaccination with a live vaccine, the screening period may be extended but cannot exceed 8 weeks. Treatment with any investigational agent within 24 weeks of screening or five half-lives of the investigational drug. Contraindications to or intolerance of oral or i.v. corticosteroids. Treatment with dalfamipridine unless on stable dose for ≥ 30 days prior to screening. Patients should remain on stable doses throughout the 48 weeks’ treatment period. Previous treatment with B-cell targeted therapies (i.e. rituximab, ocrelizumab, atacicept, belimumab or ofatumumab). Systemic corticosteroid therapy within 4 weeks prior to screening. Any previous treatment with anti-CD4, cladribine, mitoxantrone, daclizumab, teriflunomide, laquinimod, total body irradiation or bone marrow transplantation. Treatment with cyclophosphamide, azathioprine, mycophenolate mofetil (MMF), cyclosporine, methotrexate or natalizumab within 24 months prior to screening. Patients previously treated with natalizumab will be eligible for this study only if duration of treatment with natalizumab was < 1 year. Treatment with fingolimod or dimethyl fumarate (DMF) within 4 weeks prior to screening. Only patients with T lymphocyte count ≥ LLN will be eligible for this study. Treatment with I.V. immunoglobulin within 12 weeks prior to baseline. Positive serum β hCG measured at screening. Positive screening tests for hepatitis B CD4 count < 300/μL. AST/SGOT or ALT/SGPT ≥ 2.0 Upper Limit of Normal (ULN). Platelet count <100,000/μL (<100 x 109/L). Levels of serum IgG <%18 of LLN Levels of serum IgM <%8 of LLN Total neutrophil count <1500/μL. G35 Multiple sclerosis (of):NOSbrain stemcorddisseminatedgeneralized Treatment - Drugs Treatment - Drugs Intervention group: Ocrelizumab (CinnaGen, Iran) 600 mg (given as dual infusions of ocrelizumab 300 mg on Days 1 and 15 of the first 24-week treatment cycle and as single infusions of 600 mg on Day 1 for each 24-week treatment cycle, thereafter) every 24 weeks, intravenously at weeks 0, 2, 24, 48 and 72 Intervention group: Ocrelizumab (Roche, Switzerland) 600 mg (given as dual infusions of ocrelizumab 300 mg on Days 1 and 15 of the first 24-week treatment cycle and as single infusions of 600 mg on Day 1 for each 24-week treatment cycle, thereafter) every 24 weeks, intravenously at weeks 0, 2, 24, 48 and 72. Evaluate Annualized Relapse Rate. Timepoint: at weeks 0, 2, 12, 24, 48. Method of measurement: Physical examination and record the symptoms. The time to onset of sustained disability progression. Timepoint: at weeks 0, 2, 12, 24, 48, 72 and 96. Method of measurement: Neurological examination. The time to onset of sustained disability progression. Timepoint: at weeks 0, 2, 12, 24, 48, 72 and 96. Method of measurement: Neurological examination. The proportion of relapse-free patients. Timepoint: by 96 weeks. Method of measurement: Statistical analysis. The total number of new Gadolinium (Gd)-enhancing lesions as detected. Timepoint: week 24, 48 & 96. Method of measurement: by brain MRI. The total number of new, and/or enlarging T2 hyperintense lesions. Timepoint: week 24, 48 & 96. Method of measurement: by brain MRI. The change in total T2 lesion volume. Timepoint: from baseline to week 96. Method of measurement: by brain MRI. Evaluate Advarese Events. Timepoint: Every 12 weeks during the 96-week. Method of measurement: Clinical monitoring. Evaluate injection site reactions. Timepoint: Every 24 weeks during the 96-week. Method of measurement: Clinical monitoring. Evaluate the immunogenicity of the Ocrelizumab. Timepoint: week 24, 48 & 96. Method of measurement: ELISA. CinnaGen company Approved 2019-05-24 The Ethics Committee of Tehran University of Medical Sciences Qods St., Keshavarz Blvd Tehran Tehran Iran (Islamic Republic of) Approved 2019-07-21 The Ethics Committee of Shahid Beheshti University of Medical Sciences Arabi Ave, Daneshjoo Blvd, Velenjak Tehran Tehran Iran (Islamic Republic of)