This study investigates the effect of Denosumab treatment compared to treatment with placebo, in patients with Thalasemia Major and Osteoporosis

Phase 1

• Conditions: Adult patients with Thalassemia major and osteoporosis; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2014-000931-18-GR
• Lead Sponsor: Ersi Voskaridou-Dimoula

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04-03
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

•BMD T-score < -4.0 in one of the 3 studied sites (lumbar spine, femoral neck, wrist).
•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).
•Subjects with sickle-cell traits
•Known to have a liver failure or chronic hepatic disease e.g. cirrhosis, chronic hepatitis; or elevated transaminases defined as ALT and/or AST > 2 fold the upper limit of normal laboratory range; or elevated direct bilirubin > 1.5 x 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.
•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 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 malabsorptin including Celiac disease, Short Bowel Syndrome, Crohn's disease, Previous Gastric Bypass.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to evaluate the effect of Denosumab (plus vitamin D & calcium) on lumbar spine BMD in patients with Thalassemia Major and Osteoporosis as compared with control (placebo plus vitamin D & calcium) at 12 months.;Secondary Objective: 1) To evaluate the effect of Denosumab (plus vitamin D & calcium) on femoral neck and wrist bone BMD in patients with Thalassemia Major and Osteoporosis as compared with control (placebo plus vitamin D & calcium) at 12 months.<br>2) To evaluate the effect of Denosumab on markers of bone remodeling of patients with ThalassemiaMajor and Osteoporosis.<br>3) To evaluate the safety profile of Denosumab in patients with Thalassemia ajor and Osteoporosis.<br>;Primary end point(s): The primary efficacy endpoint is the percent change from baseline in the lumbar spine BMD.;Timepoint(s) of evaluation of this end point: at month 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Percent change from baseline in BMD of the total hip and femoral neck .<br>2. Percent change from baseline in BMD at the distal third radius.<br>3 Percent change from baseline in sCTX.;Timepoint(s) of evaluation of this end point: 1. At month 12.<br>2. At month 12.<br>3. At month 3 post injection.