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IRCT20150303021315N21 IRCT 2021-01-06 AryoGen Pharmed Co. Evaluation of efficacy and safety of Denosumab (produced by AryoGen Pharmed Co.) versus Denosumab (Xgeva®, produced by Amgen Co.) A Phase III, randomized, two armed, double-blind, parallel, active controlled, non-inferiority clinical trial to compare efficacy and safety of Denosumab (produced by AryoGen Pharmed Co.) versus Denosumab (Xgeva®, produced by Amgen Company) in breast cancer patients with bone metastasis 2021-02-03 anticipated 272 Complete https://irct.ir/trial/48838 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 stratification, permuted block (length of each block is 2), and R-CRAN software (version 3.2.3) that will be designed to achieve the overall balance between groups; randomization will be stratified according to prior Skeletal Related Event (SRE), prior oral bisphosphonate use, and current chemotherapy (chemotherapy treatment from 6 weeks prior randomization until the randomization date). 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 2 first letters of the first name, the 2 first letters of the first surname) and 3 numbers (center code). Moreover, the code is followed by study unique identification consisting of the first three letters of the generic name of the investigational product (which is DEN-) and 3 numbers (corresponding to the randomization number), e.g. ABCD001DEN-001. The randomization number will be assigned in a consecutive way. Each Denosumab drug packages (allocated to each patient’s injection) will have an exclusive code. Also, CRO (Contract Research Organization) will monitor the way of patient’s drug allocation in treatment groups, Blinding description: The participants, physicians, nurse (for injection) and those who assess the study outcomes will be unaware of the state of the patient with regard to receiving Denosumab (AryoGen) or Denosumab (Xgeva®). The drug packaging type is vial, therefore the drug will be exclusively prepared in similar syringes for injection by the nurse who opens the drug packages (blinding nurse). Another nurse who injects the drug will remain blind throughout the study. Thus, the process by which the drug will be prepared, make it impossible to identify the brand of Denosumab 120 mg for the patients and investigators. 3 Breast cancer. Intervention 1: Denosumab (produced by AryoGen Pharmed Co.), Subcutaneous, 120 mg once every 4 weeks for 80 weeks (21 doses). Intervention 2: Xgeva®(produced by Amgen Co.), Subcutaneous, 120 mg once every 4 weeks for 80 weeks (21 doses). 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 Nassim Anjidani
No 42, Attar St., Vanak Sq.
Tehran Iran (Islamic Republic of) 1994766411 +98 21 4347 3000 anjidani.n@orchipharmed.com Orchid Pharmed Co. scientific Pedram Fadavi
Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran
Tehran Iran (Islamic Republic of) 1415935153 +98 21 86701 Fadavi.p@iums.ac.ir Iran 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) Female patients aged 18-75 years old at the time of signing informed consent form ICF History or known case of breast adenocarcinoma Radiographic evidence of at least one bone metastasis Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. Adequate organ function: Albumin-adjusted serum calcium ≥ 2.0 mmol/L [≥ 8.0 mg/dL] and ≤ 2.9 mmol/L [≤ 11.5 mg/dL], Serum aspartate aminotransferase (AST) ≤2.5 ULN, Serum alanine aminotransferase (ALT) ≤2.5 ULN, Serum total bilirubin ≤2 ULN, Creatinine clearance ≥30 mL/min (stage 1-3 CKD patients), Serum Creatinine ≤1.5 ULN, Leukocytes > 3,000/mcL (without growth factor), Platelets > 100,000/mcL, Hemoglobin ≥8 g/d 18 years 75 years Female Planned radiation therapy or bone surgery Life expectancy less than 6 months Known brain and liver metastasis Prior administration of Denosumab or IV bisphosphonates Non-healed dental/oral surgery History or current evidence of osteonecrosis/osteomyelitis of the jaw Active dental or jaw condition which requires oral surgery Planned invasive dental procedure in the course of the study Disorders associated with abnormal bone metabolism including uncontrolled hyperthyroidism or hypothyroidism or Paget’s disease Prior malignancy (other than breast cancer, basal cell carcinoma, or in situ cervical cancer) within 3 years prior to randomization Known infection with human immunodeficiency virus (HIV) Known infection with Hepatitis B or Hepatitis C virus (HBV or HCV) Receiving any investigational product or device in other clinical trials 30 days prior to the study Allergy to any of the products to be administered during the study (eg, Denosumab, mammalian cell line products, calcium or vitamin D) Treatment with calcitonin, parathyroid hormone-related peptides, mithramycin, strontium ranelate, or gallium nitrate within 8 weeks prior to randomization Any psychiatric disorder, organ disfunction or systemic disease that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results Pregnancy or breast feeding C50.919 Malignant neoplasm of unspecified site of unspecified female breast Treatment - Drugs Treatment - Drugs Denosumab (produced by AryoGen Pharmed Co.), Subcutaneous, 120 mg once every 4 weeks for 80 weeks (21 doses) Xgeva®(produced by Amgen Co.), Subcutaneous, 120 mg once every 4 weeks for 80 weeks (21 doses) Time to first on-study Skeletal-Related Event (SRE). Timepoint: During a 21 months period (with monthly physician visits and imaging every 3 months). Method of measurement: The time from the date of randomization to first SRE including date of pathologic fracture, radiation or surgery to bone, or spinal cord compression. Time to first and subsequent (multiple) Skeletal Related Event (SRE). Timepoint: During a 21-month period (with monthly physician visits and imaging every 3 months). Method of measurement: The time from the date of randomization to first and subsequent SRE. Safety Outcomes. Timepoint: During a 21-month period. Method of measurement: Safety will be assessed based on clinical examinations and laboratory test results. Immunogenicity. Timepoint: Weeks 0, 24, 52, 84. Method of measurement: Blood test and antidrug antibody (ADA) presence evaluation. AryoGen Pharmed Co. Approved 2020-06-22 Iran University of Medical Sciences Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran Tehran Tehran Iran (Islamic Republic of) Approved 2020-12-03 Shahid Beheshti University of Medical Sciences Shahid Beheshti University, Daneshjou Boulevard, Tehran, Tehran Province Tehran Tehran Iran (Islamic Republic of)