Clinical trial: Clinical Efficacy and Safety Comparative Study Between CMAB807 Injection and Prolia® . (NCT04591275)

Eligibility 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: -4.0<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.
Female
No healthy subjects accepted to join the trial.
Subject must be at least 50 Years old.
Subject must be at most 85 Years

Patient description (medical language): A 55-year-old white woman comes for a routine checkup.  She has no significant medical history and does not use tobacco, alcohol, or illicit drugs.  The patient's only medication is an over-the-counter multivitamin.  Family history is notable for a hip fracture in her mother.  Blood pressure is 130/80 mm Hg and pulse is 112/min. She has occasional back pain and lives a sedentary lifestyle with the BMI of 24 Kg/m2. Plain X-ray of the spine shows mild compression fracture at the level of T10. X-ray absorptiometry studies demonstrate abnormally low bone density in the lumbar vertebrae and T-score values below -2.5, which confirms the diagnosis of osteoporosis.

Patient description (patient's own words): I'm a 55-year-old white woman and I recently visited my family doctor. I don't smoke anything or drink. I don't have any remarkable medical history. I only use over-the-counter multivitamins to keep myself fresh and energized. My mom had a hip fracture. The doctor took my blood pressure and it was 130/80 and my pulse was 112/min. I have annoying back pain from time to time and to be honest I don't exercise much or move much. My BMI is 24. I did a spine X-ray a while ago and my doctor showed me that I have a fracture on one of my vertebrae. I also have a low bone density in my lumbar vertebrae and T-score values below -2.5. The doctor diagnosed me with osteoporosis.

Does the patient match the trial criteria? Entailment