Please select the eligibility criteria that correspond to the clinical trial below.
Title: Evaluation of Efficacy of Denosumab in Patients With Thalassemia Major and Osteoporosis: A Randomized, Placebo-controlled, Single-site, Double Blind Phase 2b Clinical Trial
Brief Summary: This is a single-site, randomized, placebo-controlled, double blind phase 2b clinical trial. Patients with Thalassemia will participate in this study and will be treated with Denosumab or placebo. The effect of Denosumab on lumbar spine BMD in patients with Thalassemia Major and Osteoporosis will be evaluated as compared with control (placebo) at 12 months.


Options:
A: 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.
B: Inclusion Criteria:

* Patients with thalassaemia or sickle cell anaemia and bone density, z-scores \< -1.5, in at least one of the examined sites
* Normal renal function. Urea and creatinine should not exceed \> 2-fold the upper limit of normal (\< 2 x ULN).

Exclusion Criteria:

-

Other protocol-defined inclusion / exclusion criteria may apply.
C: Inclusion Criteria:

* 6 to 30 years of age
* thalassemia
* bone mineral density Z-score \< -1.0 (by DXA)

Exclusion Criteria:

* Bone marrow transplant recipient
* Currently prescribed treatment for low bone mass other than calcium or vitamin D (e.g. calcitonin, bisphosphonates)
* Currently prescribed zinc supplementation who are unable or unwilling to stop during this trial
* Currently participating in another trial with a medication known to affect bone mineral density.
* Chronic use of systemic corticosteroids
* Untreated hypogonadism or growth hormone deficiency
* Baseline serum copper \< 70 µg/dL
* Baseline vitamin D-25OH \< 11 ng/mL
* Pregnant or lactating at study entry
D: Inclusion Criteria:

* Patients presenting BMD Z score \<-2 at the level of the femoral neck or of the lumbar column Regular transfusional regimen in order to mantain pre-transfusional Hb values \>9 g/dl.

Written informed consent by the patient

Exclusion Criteria:

Entravenous administration of bisphosphonates within the past 2 years

Administration of di bisphosphonates per os, unless wash out as it follows:

1 year if \>8 weeks \<48 weeks 6 months if \> 2 weeks and \<8 weeks Hypoparathyroidism Thalassemia Intermedia if not regularly transfused Pregnancy and breast feeding Impaired renal function (creat. \> 1.5 mg/dl) Neoplastic disease Patients with mean levels of alanine aminotransferase ALT \> 300 U/l and patients with variations of AST or AST of 300% within the year before randomization. (At least 4 misurations over 12 months) Systemic cardiovascular, renal, hepatic disease etc. which would prevent the patient from undergoing study treatment Known hypersensibility to bisphosphonates. History of non compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative.

Answer: A