Clinical Efficacy and Safety Comparative Study Between CMAB807 Injection and Prolia® .

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: Female

Summary

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Biomabs Pharmaceutical Co., Ltd.
• Treatments: Denosumab

Criteria

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: -4.05. 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 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.