Clinical trial NCT02559648 (phase 2, status: completed)
Conditions: thalassemia major, osteoporosis
ICD codes: D56.0, D56.1, D56.3, D56.9, D56.2, D56.5, D57.40, M81.6, Z82.62, Z13.820, M81.8, Z87.310, M81.0, M80.80XS
Drugs: denosumab, placebo
SMILES: CC(=O)OC1=CC=CC=C1C(O)=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        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.