Denosumab vs Placebo in Patients With Thalassemia Major and Osteoporosis

This is an interventional treatment trial for Thalassemia Major Read More

Inclusion Criteria:

• Adults (>30 years of age) described as skeletally mature subjects
• Thalassemia Major
• Low BMD (T-score <-2.5) in one of the 3 studied sites (lumbar spine, femoral neck, wrist).
• Have signed the informed consent form (consent should be taken before any study-specific procedure is performed).

Exclusion Criteria:

• BMD T-score < -4.0 in one of the 2 studied sites (lumbar spine, femoral neck).
• Previous administration of denosumab from clinical trials or others (e.g. commercial use).
• Current participation in another clinical trial or having received any investigational product within the last 3 months.
• Impaired renal function as determined by an estimated glomerular filtration rate (eGFR) of ≤ 30 mL/min (using the Chronic Kidney Disease-Epidemiology, ((CKD-EPI) formula).
• Patients with sickle cell disease.
• Known to have a liver failure or chronic hepatic disease e.g. cirrhosis, chronic hepatitis; or elevated transaminases defined as Alanine Transaminase (ALT) and/or Aspartate Transaminase (AST) > 2 fold the upper limit of normal laboratory range.
• Heart failure (NYHA above 2).
• Patients with life expectancy of less than one year.
• Subject refuses to use a reliable contraceptive method (oral contraceptives, progesterone implants, intrauterine device, condoms) throughout the study by women of childbearing potential. Women of childbearing potential agree to use 2 highly effective forms of contraception and to continue this practice for 7 months after last injection of study medication.
• Pregnancy, planning a pregnancy or currently lactating
• Severe concurrent illness which in the investigator's opinion may confound patient evaluation, e.g. malignancy (except basal cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years.
• Known alcohol or drug abuse or any other condition associated with poor compliance
• Patients that have received oral bisphosphonates within 6 months of study enrollment or intravenous bisphosphonates, fluoride and strontium ranelate within 1 year of study enrollment.
• Parathormone (PTH), PTH derivatives, teriparatide, odanacatib, anabolic steroids, testosterone, glucocorticosteroids (> 5 mg/day of prednisone equivalent for > 10 days), systemic hormone-replacement therapy, selective estrogen receptor modulators (SERMs), raloxifene, tibolone, calcitonin or calcitriol use within the last 6 weeks.
• Evidence of hyper- or hypothyroidism; patients with an abnormal Thyroid stimulating hormone (TSH) level on thyroid treatment (patients on stable thyroid treatment with a normal TSH allowed); current hyper- or hypoparathyroidism; current hyper or hypocalcemia (hypocalcemia based on albumin adjusted serum calcium < 8.5 mg/dL); vitamin D deficiency (25-hydroxy Vitamin D level < 12 ng/mL; if repeat 12-20 ng/mL after repletion, subject will be allowed); rheumatoid arthritis; Paget's disease; bone disease that would interfere with interpretation of findings.
• Known sensitivity to mammalian cell-derived drug products.
• History of any Solid Organ or Bone Marrow Transplant
• History of osteonecrosis of the jaw, and/or recent tooth extraction or other dental surgery; or planned invasive dental work during the study.
• Intolerance to calcium supplements.
• Malabsorption syndrome; severe malabsorption including Celiac disease, Short Bowel Syndrome, Crohn's disease, Previous Gastric Bypass.