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IRCT2017020521315N9 IRCT 2017-03-12 AryoGen Pharmed company Effect of denosumab administration (produced by Amgen or AryoGen Pharmed) in improvement of bone mineral densitometry (BMD) among osteoporotic postmenopausal women. A Phase III, randomized, two armed, parallel, double blind, active controlled, non-inferiority clinical trial to determine the non-inferior therapeutic efficacy and safety between Denosumab (60 mg, produced by AryoGen Pharmed) compared with Prolia® (60 mg, Denosumab, the reference drug, produced by Amgen Company) in improvement of bone mineral densitometry (BMD) among osteoporotic postmenopausal women 2017-04-21 anticipated 190 Complete https://irct.ir/trial/18715 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. Using permuted block randomization, blocks (length of each block is 4 or 2) will be made, for a total of 190 patients (with 1:1 allocation ratio). Once the randomization has been made, each patient is given a code with which she will be identified throughout the study. The assigned code will be made up of 3 numbers (corresponding to the randomization number) and by 4 initials (corresponding to the 2 first letter of the first name, the 2 first letter of the first surname) and 2 numbers (center code). The randomization number will be assigned in a consecutive way, Blinding description: To prevent the influence of knowing intervention group on study conclusion, the subjects and those who assess the study outcomes will be unaware of the state of the patient with regard to receiving the active drugs or standard remedy. For this purpose, subjects and administrator of the drug will be blinded by using a similar masked prefilled syringes. All drugs packages will be identified by unique numbers. 3 Postmenopausal osteoporosis. Intervention 1: Denosumab (produced by AryoGen Pharmed) prefilled syringe for patients with dose of 60 mg, subcutaneous (S/C) injection every 6 months, at the beginning of the trial, month 6 and 12. Intervention 2: Prolia® (produced by Amgen Company) prefilled syringe for patients with dose of 60 mg, subcutaneous (S/C) injection every 6 months, at the beginning of the trial, month 6 and 12. No - There is not a plan to make this available Justification or reason for not sharing IPD is The company have no plan to do this
public Ramin Azhdarzadeh
No.2, khorasani Alley, Derakhti Ave, dadman blvd, Shahrak-e-Gharb
Tehran Iran (Islamic Republic of) 1468813112 +98 21 8808 8821 azhdarzadeh.m@orchidpharmed.com Orchid Pharmed company scientific Ahmadreza Jamshidi
Shariati Hospital, Jalal Al Ahmad Highway, Tehran, Iran.
Tehran Iran (Islamic Republic of) 1411713137 +98 21 8800 5141 jamshida@sina.tums.ac.ir Rheumatology Research Center, Shariati Hospital. 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) Postmenopausal women aged between 45 up to 75. Bone mineral density T score at the lumbar spine (L1-L4), femoral neck or total hip should be equal or less than -2.5 and equal or more than -4. (-4 ≤T score ≤−2.5); or patients with high risk of fracture on the basis of FRAX criteria which according to osteoporosis treatment guidelines, need medicinal treatment Ability to comprehend and willingness to sign the Informed Consent Form for this study; Signed informed consent with full knowledge and mental health. 45 years 75 years Female Lack of consent for being in the trial and not complying with an 18-months follow-up. Having hypersensitivity to denosumab or any component in the formulation (excipients include acetic acid, sorbitol, Polysorbate 20, sodium hydroxide, water for injections) Malabsorption syndrome History of thyroid surgery, parathyroid surgery or intestinal resection which has been caused malabsorption Patient with CKD stage 4 and 5 should be excluded (GFR <30cc/min) Level of serum 25-(OH) vitamin D less than 20 ng/ml; (If vitamin deficiency has been corrected, and two tests show the level above 20 ng/ml within a month, the patient can be enrolled.) Pre-existing hypocalcemia (Albumin-adjusted serum calcium level less than 8 mg/dl in fasting specimens) which is uncorrectable Untreated hypercalciuria (>250 mg/24h) and hypocalciuria (<100 mg/24h). If urine calcium level of patient is less than 100 mg per 24 hours and by vitamin D treatment the problem has been solved or if urine calcium level of patient is greater than 250 mg per 24 hours, but PTH is normal, the patient can be enrolled Presence of osteonecrosis of jaw (ONJ) risk factors including a diagnosis of cancer, poor oral hygiene, periodontal and/or dental diseases, having dentures; and comorbid disorders (anemia (hemoglobin level less than 11 g/dl, if it is corrected, patient can enter the study) history of diseases with coagulopathy, oral and dental infection) Malignancy Having severe and active infections; (Severe infection is a difficult treated infection, like diabetic foot infection, but if the infection is treatable, after treatment, the patient can be enrolled.) Being bed rest (for 2 weeks during the past 3 months) A case in which the patient cannot take 1000 mg oral elemental calcium per day; (as supplement) Conditions that influence bone metabolism, including hyperparathyroidism or hypoparathyroidism, hyperthyroidism or hypothyroidism, hypocalcemia, inflammatory rheumatologic diseases such as rheumatoid arthritis, Paget’s disease of bone, osteomalacia that is resistant to therapy (definition of resistant to therapy: not being responder to 1-month administration of vitamin D) Patients will be excluded if they have one severe or more than 2 moderate vertebral fractures. (Severe fracture is defined as more than 50 percent vertebral height loss and moderate fracture is defined as 25-50 percent vertebral height loss). Use of injectable bisphosphonates within the previous 12 months Use of oral bisphosphonates within the previous 3 months History of severe skeletal pain with bisphosphonates Use of parathyroid hormone or its derivatives, systemic hormone-replacement therapy, selective estrogen-receptor modulator, calcitonin, or calcitriol within 6 weeks before study enrollment. Use of corticosteroids (>5 mg/prednisone daily or equivalent for ≥ 3months), in the past 3 months and more Use of heparin (more than 20,000 international units/day for 6 months and longer), in the past 6 months and more. Patient that is possible to be administrated corticosteroids (>5 mg/prednisone daily or equivalent for ≥ 3months) or heparin (more than 20,000 international units/day for 6 months and longer) in the 18 month of the study, because of her chronic disease(s) such as allergy, asthma, coagulation disorders, should be excluded. M80.0 Postmenopausal osteoporosis Treatment - Drugs Treatment - Drugs Denosumab (produced by AryoGen Pharmed) prefilled syringe for patients with dose of 60 mg, subcutaneous (S/C) injection every 6 months, at the beginning of the trial, month 6 and 12. Prolia® (produced by Amgen Company) prefilled syringe for patients with dose of 60 mg, subcutaneous (S/C) injection every 6 months, at the beginning of the trial, month 6 and 12. Percentage change in BMD at the lumbar spine (L1-L4), femoral neck, and total hip. Timepoint: Baseline and at 18th month of the study. Method of measurement: BMD by dual-energy x-ray absorptiometry Hologic 4500 or higher. Adverse events ocurrance. Timepoint: all of the visit ( 1-9). Method of measurement: Physical examination, physician Assessment, and laboratory tests. Level of biochemical markers of bone metabolism (Serum CTX, Serum NTX, P1NP, OC, BSAP). Timepoint: Before injection at visit 2, 3, 4, 5, 6, 7, 8 and 9. Method of measurement: ELISA method. The incidence of new vertebral fracture. Timepoint: The incidence of new vertebral fracture at baseline and at 18th month of the study. Method of measurement: X-ray radiography. Immunogenicity of two products. Timepoint: Before the injections, at visit 2, 5, 7 and 9. Method of measurement: ELISA method. AryoGen Pharmed company Approved 2017-01-31 Ethics committee of Tehran university of medical science First floor, NO 21,Dameshgh st, Felestin st.Keshavar Blv Tehran Tehran Iran (Islamic Republic of) Approved 2016-10-10 Ethics committee of Tabriz university of medical science School of medicine, Tabriz university of medical sciences, Tabriz Tabriz East Azarbaijan Iran (Islamic Republic of)