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

Objectives: Compare the efficacy of Denosumab produced by Aryogen Company and Amgen Prolia® in subjects with osteoporotic postmenopausal women. Patients with diagnosis of osteoporotic postmenopausal women according to Bone mineral density T score at the lumbar spine (L1-L4) or total hip should be equal or less than -2.5 and more than -4, or patients who need drug treatment based on the criteria of FRAX according to osteoporosis treatment guidelines with a high risk of fracture, aged 45 to 75 years will be included. Design & Setting and conduct: This study is a randomized, double blind clinical trial in which Denosumab is administered subcutaneously 60 mg every 6 months for 190 eligible women patients over 18 months. Participants including major eligibility criteria: Inclusion criteria including Postmenopausal women aged between 45 up to 75; Bone mineral density T score at the lumbar spine (L1-L4) or total hip should be equal or less than -2.5 and more than -4, or patients who on the criteria of FRAX, need drug treatment; Ability to comprehend and willingness to sign the Informed Consent Form for this study and Exclusion criteria including, Lack of consent for being in the trial; Having hypersensivity to denosumab; Malabsorption syndrome; History of thyroid surgery, parathyroid or intestinal resection; Patient with CKD stage 4 and 5 should be exclude; Level of vitamin D less than 20 ng/ml; Untreated hypercalciuria (>250 mg/24h) and hypocalciuria (<100 mg/24h); Presence of osteonecrosis of jaw (ONJ) risk factors including a diagnosis of cancer, poor oral hygiene, periodontal and/or dental diseases; Malignancy; severe and active infections; Being bed rest; intolerable of taking 1000 mg oral calcium per day; A case in which bone mineral density could not be accurately measured; hyperparathyroidism or hypoparathyroidism, hyperthyroidism or hypothyroidism, hypocalcemia, inflammatory rheumatologic diseases; one severe or more than 2 moderate vertebral fractures; 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 in the past 3 months and more ; Use of heparin in the past 6 months and more; Patient that is possible to be administrated corticosteroids or heparin in the 18 month of the study, such as allergy, asthma, coagulation disorders, should be excluded Intervention: All the participants will receive one of the following regimens; group 1, Denosumab produced by AryoGen Pharmed and group 2, Prolia® produced by Amgen Company for patients with dose of 60 mg, subcutaneous (S/C) injection every 6 months, at the beginning of the trial, month 6 and 12. Main outcome measures (variables): Assessment of efficacy Parameters of Denosumab compared with Prolia® and according to Percentage change from baseline in BMD at lumbar spine (L1-L4) and total hip by dual-energy x-ray absorptiometry at 18 months of the study

Aryogen Company