Efficacy and Safety of JMT103 in the Treatment of Glucocorticoid Induced Osteoporosis

Inclusion Criteria:

• 1. Both genders aged 18 years or above, capable of autonomous action;
• 2. In the course of an ongoing glucocorticoid treatment for at least 3months with prednisone≥7.5 mg or its equivalent taken currently, and expected to be treated of no less than 6 months in total;
• 3. Any of the followings: a. History of osteoporotic fracture; b. Age≥50 years and lumbar (L1-L4) or total hip BMD of T≤-2.0 by DXA; c. Age≥40 years and a predicted 10-year risk of major osteoporotic fractures ≥ 10% (vertebral body, forearm, hip, shoulder) or a predicted 10-year risk of hip fracture ≥ 1% estimated by hormone adjusted FRAX;
• 4. At least two lumbar vertebrae from L1 to L4 evaluable by DXA;
• 5. Uncompromised ability to maintain good communication with investigator and comply with all required study procedures;
• 6. A signed informed consent under the capability of thorough understanding.

Exclusion Criteria:

• 1. Currently pregnant or lactating; For those of child bearing potential, refusal to use effective forms of contraception from signing informed consent to 6 months after last administration;
• 2. Previous or ongoing osteomyelitis or necrosis of jaw; Unhealed dental/oral operation wound; Acute jaw bone or dental disease requiring oral surgery; Planned invasive dental surgery during the study period;
• 3. Selected into other clinical studies of which the latest administration is less than 4 weeks (or 5 elimination half-lives, whichever is longer) from the first administration in this study;
• 4. Intravenous use of bisphosphonates, fluoride or strontium in the past 5 years; Oral bisphosphonates use for more than 3 years in total, or between 3 months to 3 years in total with the last medication used in the past 1 year prior to signing informed consent;
• 5. Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) antibody used within 6 months prior to screening;
• 6. Administration of any of the following bone metabolism affecting drugs within 3 months prior to screening: a. Parathyroid hormone (PTH) or PTH derivatives (e.g., teriparatide); b. Anabolic hormones or testosterone; c. Sex hormone replacement; d. Selective estrogen receptor modulators (SERMs, e.g., raloxifene); e. Calcitonin; f. Other bone metabolism activating drugs include anticonvulsants (except benzodiazepines) and heparin; g. Long-term systemic use of ketoconazole, adrenocorticotropic hormone (ACTH), cinacalcet, aluminium, lithium, protease inhibitor, methotrexate or gonadotropin releasing hormone agonist;
• 7. Administration of any of the following biologic agents within 4 weeks prior to screening: a. Anti-alpha 4 integrin antibody (e.g., natalizumab); b. Anti CD4/CD8 T-cells (e.g., alefacept); c. Anti-IL12/anti-IL23 (e.g., ustekinumab); d. CTLA4 inhibitor (e.g., abatacept); e. IL1 receptor antagonist (e.g., anakinra); f. IL6 inhibitor (e.g., tocilizumab); g. Monoclonal antibody to CD20 (e.g., rituximab); h. TNF antagonist (e.g., adalimumab, certolizumab, golimumab, etanercept, infliximab);
• 8. Requirement of >1 biologic agent (other than trial drug) for the treatment of underlying inflammatory disease;
• 9. Bone metabolic disorders (other than osteoporosis alone): a. Hypo- or hyperparathyroidism; b. Osteogenesis imperfecta; c. Malignant tumor; d. Hypopituitarism; e. Hyperprolactinemia; f. Acromegaly; g. Paget disease of bone;
• 10. Hyperthyroidism or hypothyroidism, except for a stable replacement therapy for at least 3 months turning out a normal ranged TSH or increased TSH≤10.0 μIU/mL with normal ranged FT4;
• 11. Malabsorption syndrome or various gastrointestinal diseases associated with malabsorption, such as Crohn's disease and chronic pancreatitis
• 12. Liver cirrhosis or unstable liver disease (defined as ascites, hepatic encephalopathy, coagulation disorder, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice); Known or clinically significant biliary abnormalities judged by investigator (except Gilbert syndrome, asymptomatic gallstones and gallbladder polyps);
• 13. Previous organ or bone marrow transplantation;
• 14. Unwilling to take vitamin D and calcium supplements as the procedure requires;
• 15. Uncontrolled concurrent diseases, including but not limited to: uncontrolled diabetes (> 2 grade according to NCI-CTCAE5.0), symptomatic congestive heart failure, hypertension with blood pressure greater than 150/90 mmHg after standard treatment, unstable angina pectoris, arrhythmia requiring medication or instrument treatment, myocardial infarction history within 6 months, and echocardiography with left ventricular ejection fraction < 50%;
• 16. 25[OH] vitamin D level < 20 ng/mL, retest allowed after 5000 iu/day vitamin D added for 4-6 weeks;
• 17. Current hypocalcemia or hypercalcemia, defined as albumin-corrected serum calcium level of ≤ 2.2 mmol/L (8.8 mg/dL) or ≥ 2.9 mmol/L (11.5 mg/dL) (no supplementation of calcium for at least 8 hours before test);
• 18. Serum whole parathyroid hormone (iPTH) > 65 pg/mL;
• 19. Any of the followings: a. Routine blood test (shall no treatment such as blood transfusion or hematopoietic stimulating factor was received within 7 days): absolute neutrophil count < 1.5×10^9/L, platelet < 75 × 10^9/L, or hemoglobin < 90 g/L; b. Liver function test: total bilirubin > 1.5 × upper limit of normal value (ULN), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULN (retest allowed after 2-4 weeks for AST and ALT); c. Renal function test: estimated glomerular filtration rate (eGFR) < 35 L/(min·1.73m^2); d. Coagulation function test: activated partial thromboplastin time > 1.5 × ULN, or international normalized ratio (INR) > 1.5 × ULN;
• 20. Active bacterial or fungal infections requiring systematic treatment within 7 days prior to randomization;
• 21. HIV infection, active hepatitis, known or suspected active tuberculosis;
• 22. Any malignant tumor within 5 years prior to screening, except those expected to be cured (e.g., completely resected in situ skin basal cell or squamous cell carcinoma, cervical cancer or breast ductal cancer, etc.);
• 23. Known allergic/hypersensitive reaction or intolerance to JMT103, positive control drug, calcium and vitamin D;
• 24. Contraindicated to alendronate therapy: abnormalities of the esophagus which delay esophageal emptying (e.g., stricture or achalasia), or inability to stand or sit upright for at least 30 minutes;
• 25. BMD measurement by DXA interrupted: < 2 measurable lumbar vertebrae; Interrupting height, weight or waist circumference; Severe scoliosis and other measurement affecting conditions;
• 26. Considered unsuitable for the research project by investigator.