A Study on Efficacy, Safety and Immunogenicity of 9MW0311 in Postmenopausal Women With Osteoporosis

A Randomized, Double-blind, Parallel-group, Phase III Study to Compare the Clinical Efficacy, Safety, and Immunogenicity of Denosumab Injection 9MW0311 With Prolia® in Postmenopausal Women With Osteoporosis

This study is a multicenter, randomized, double-blinded, parallel-group Phase III clinical study to compare the clinical efficacy, safety, and immunogenicity of 9MW0311 and Prolia® in Chinese postmenopausal women with osteoporosis at high risk for fracture.

278 patients are randomized 1:1 to receive 9MW0311 and Prolia® every 6 months for 12 months. The primary efficacy endpoint is the percentage change from baseline in BMD at the lumbar spine(LS) in month 12.

Inclusion Criteria:

• Women who can walk freely (≥50 and ≤80 years);
• As measured by DXA, the absolute value of BMD at lumbar spine, femoral neck or total hip was -4.0<T value ≤-2.5;
• Subjects must have at least one of the following other risk factors: 1) history of previous fragility fractures; 2) Either or both parents have a history of hip fragility fracture; 3) Increased bone turnover rate during screening; 4) Low body weight; 5) Old age(≥70); 6) Currently smoking.
• The duration of spontaneous amenorrhea was >2 years or >2 years after bilateral oophorectomy. If the status of bilateral oophorectomy is unknown or if the ovaries are preserved after hysterectomy, follicle stimulating hormone (FSH) levels >40mIU/mL may be used to confirm the status of postoperative menopause.

Exclusion Criteria:

• Bone/metabolic disease

• Hyperparathyroidism or hypoparathyroidism

• Thyroid condition: Hyperthyroidism or hypothyroidism

• Rheumatoid arthritis

• Malignant tumors

• Malabsorption syndrome

• Liver cirrhosis, active hepatitis B or hepatitis C, and unstable liver disease; serum aspartate aminotransferase and alanine aminotransferase ≥ 2.0 times the upper limit of normal (ULN); alkaline phosphatase or total bilirubin ≥ 1.5 ULN;

• Renal disease - severe impairment of kidney function

• Clinically significant cardiovascular and cerebrovascular diseases (such as myocardial infarction, unstable angina or stroke, NYHA class III or IV heart failure in the 12 months prior to screening) and hematopoietic system disease judged by the investigator;

• Hypercalcemia or hypocalcemia ;

• vitamin D deficiency (25-hydroxyvitamin D, 25OHD <20 ng/mL);

• Oral or dental diseases: previous or current evidence of mandibular osteomyelitis or osteonecrosis; Acute dental or mandibular disease requiring oral surgery; Planning invasive dental surgery; Failure to recover from dental or oral surgery;

• Use of intravenous bisphosphonates within the previous 2 years;

• oral bisphosphonates (used for at least 2 years, or used for less than 2 years but more than 3 months, with the last use occurring <1 year before the screening);

• Use of any of the following drugs within 6 weeks prior to screening that may affect bone metabolism:

  1. parathyroid hormone (PTH) or PTH derivatives, such as teriparatide;
  2. anabolic hormones or testosterone;
  3. glucocorticoids (equivalent dose more than 5mg/ day of prednisone and continuous use for more than 10 days);
  4. Selective estrogen receptor modulators (SERMs), such as raloxifene;
  5. Menopausal hormone therapy (such as estrogen, estrogen + progesterone, tibolone);
  6. Active vitamin D and its analogues (cumulative use of more than 30 days);
  7. Other bone-active drugs include antiepileptic drugs (except benzodiazepines) and heparin;
  8. Long-term systemic use of ketoconazole, adrenocorticotropin (ACTH), aluminum, lithium, protease inhibitors, methotrexate, gonadotropin releasing hormone agonists;
  9. Chinese patent medicines for osteoporosis related treatment are clearly described in the instructions, such as Xianling Gubao capsule (tablet), Gushukang capsule (granule), Jintiange capsule and Qianggu capsule."

• History of more than two vertebral fractures.