Randomized, Doubel-blinded, Parallel, Active-controlled Phase III Study, to Evaluate the Efficacy and Safety of CMAB807 Treatment Compared With Prolia® in Chinese Postmenopausal Women With Osteoporosis at High Risk of Fracture.

CMAB807-III-001

evaluate the differences in effectiveness and safety between CMAB807( potential biosimilar) and Prolia(original product)

2021-03-31

2024-10-01

2024-11-01

Recruiting

Early phase I

278

Inclusion Criteria: 1. Fully informed, understood, voluntary participate, and the patient himself or guardian agree to sign the written informed consent and patient be able to comply with the protocol; 2. Aged from 50 years to 85 years, inclusive; 3. Spontaneous amenorrhea time ≥ 2 years, or bilateral oophorectomy≥ 2 years. If the status of bilateral ovariectomies is unknown, the menopause status should be confirmed by follicle stimulating hormone(FSH) level≥ 40IU/L; 4. Based on the results of dual energy X-ray absorptiometry, BMD of lumbar spine(L1\~L4), femoral neck or total hip: -4.0\<T-Score≤-2.5； 5. There must be at least one of the following risk factors: * History of osteoporotic fracture; * Father's and mother's hip fracture history, or both parents'; * Low body mass index(≤19kg/m\^2); * Patient's age was equal or greater than 70 years old; * Current smoker; * CTX1 was one standard deviation higher than that of healthy premenopausal women within screening period(ie, CTX1\>0.43ng/mL); 6. Ability to act independently. Exclusion Criteria: 1. Suffering from the following diseases known to affect calcium or bone metabolism: * Various metabolic bone diseases, such as osteogenesis imperfecta and osteomalacia; * Paget's osteopathy; * Cushing's syndrome; * Hyperprolactinemia; * Hypopituitarism; * Acromegaly; * History of hyperparathyroidism or hypoparathyroidism; * History of hyperthyroidism or hypothyroidism(hypothyroidism patients can be included: only receiving stable thyroid hormone replacement therapy, if the thyroid stimulating hormone(TSH) level is normal, or 5.5μIU/mL\<TSH≤10.0μIU/mL, and free thyroxine(FT4) is in normal range can be included); * Malabsorption syndrome or various gastrointestinal diseases associated with malabsorption, such as Crohn's disease and chronic pancreatitis; * Abnormal level of blood calcium: the current diagnosis of hypocalcemia or hypercalcemia or albumin corrected serum calcium levels are not within the laboratory normal range(calcium supplements should not be used for at least 8 hours prior to serum calcium testing); * Vitamin D deficiency: 25 hydroxyvitamin D concentration\<20ng/mL. Allowed to retest after oral vitamin D2 soft capsules in the screening period. If the concentration of 25 hydroxyvitamin D is more than or equal to 20ng/mL， it can be selected; * Other diseases such as rheumatoid arthritis, gout, multiple myeloma, etc; 2. Medical history of two or more vertebrae fractures; 3. Malignant tumor(excluding skin basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ or breast ductal carcinoma in situ) in recent 5 years; 4. Severe renal function damage(creatinine clearance rate\<30mL/min), or dialysis, urinary calculi or chronic cystitis; 5. Suffering from the following liver or biliary diseases: * Liver cirrhosis; * Biliary abnormalities(except for Gilbert syndrome or asymptomatic gallstones); * Positive hepatitis C virus antibody(HCV-Ab) and the titer of HCV-RNA exceeded the upper limit of norma; * Positive hepatitis B suface antigen(HBsAg) and peripheral blood HBV-DNA titer ≥1000 capies\[CPS\]/mL or 200IU/mL; * Unstable liver disease: defined as liver ascites, hepatic encephalopathy, coagulopathy, hypoalbuminemia, varicosis in esophagus or stomach fundus or persistent hepatic jaundice; 6. Liver transaminase: aspartate aminotransferase≥2.0×upper limit of norma value(ULN), alanine aminotransferase≥2.0ULN, alkaline phosphatase≥1.5ULN or total bilirubin≥1.5ULN; 7. Suffering from the following oral diseases: * Osteomyelitis or osteonecrosis of the jaw, previously or currently; * Actue dental or mandibular disease requiring stomatological surgery; * Planned invasive dental surgery during the trial period; * Dental or stomatological surgery have not healed; 8. Conditions which can influence bone mineral density determination by dual energy X-ray absorptiometry: * Less than two lumbar vertebrae can be measured; * Height, weight or waistline may hinder accurate measurement; * Other conditions that may affect bone density testing 9. Received anti-osteoporosis drugs or those drugs may affect bone metabolism: * Use of injectable bisphosphonates, fluoride or strontium within 2 years before screening; * Use of oral bisphosphonates: more than 2 years, or more than 3 months but less than 2 years and discontinued from last dosage less than 1 year, simultaneously; * Usage of any drugs which may affect bone metabolism within 6 weeks before screening: parathyroid hormone or parathyroid hormone analogue(such as teriparatide); assimilative hormone or testosterone; glucocorticoid(equivalent to prednisone\>5mg/day for more than 10 days); systemic hormone replacement therapy; selective estrogen receptor regulator(such as reloxifene); tibolone; calcitonin; active vitamin D and ite analogues, other bone active drugs include anticonvulsant drugs(except benzodiazepines) and he\[arin; long-term systemic use of ketoconazole, androgen, adrenocorticotropic hormone, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin releasing hormone agonist; * Patients who have received RANKL inhibitors previously; 10. Positive HIV antibody; 11. Known alcoholism or drug abuse(during 12 months before screening), because alcohol or drug abuse may interfere with subject's understanding or finish of trial; 12. Known allergy to test drug, reference drug or basic drug and its excipients; 13. Participate in interventionary clinical study(drug or device) within one month before screening; 14. Other serious, acute or chronic diseases, mental disorders or laboratory abnormalities, which are judged by investigator to be unsuitable to participate this study.

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2024-03-26