Denosumab vs Placebo in Patients With Thalassemia Major and Osteoporosis

• Status: Completed
• Trial end date: 2017-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ersi Voskaridou
• Treatments: Denosumab

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.