Evaluation of Efficacy of Denosumab in Patients With Thalassemia Major and Osteoporosis: A Randomized, Placebo-controlled, Single-site, Double Blind Phase 2b Clinical Trial
Overview
- Phase
- Phase 2
- Intervention
- Denosumab
- Conditions
- Thalassemia Major
- Sponsor
- Ersi Voskaridou
- Enrollment
- 63
- Locations
- 1
- Primary Endpoint
- The percent change in the lumbar spine BMD
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Detailed Description
This is a single-site, randomized, placebo-controlled, double blind phase 2b clinical trial. Patients with Thalassemia and Bone Mass Density (BMD) T-score between -2.5 and - 4.0 in at least one of the examined sites will participate in this study and will be treated with Denosumab or placebo. Patients will be assigned into two (2) treatment groups: * In Group A, 60 mg Denosumab will be administered sc, every 6 months for 12 months for a total of 2 doses (day 0 and day 180). * In Group B placebo will be administered sc, every 6 months for 12 months for a total of 2 doses (day 0 and day 180) (Appendix I and Appendix II). Patients will be randomly assigned, in a 1:1 fashion, to the two therapeutic arms (Group A, Group B, respectively), upon enrollment in the study. The effect of Denosumab on lumbar spine BMD (bone mineral density) in patients with Thalassemia Major and Osteoporosis as compared with control at 12 months will be evaluated. Also the effect on femoral neck and wrist bone BMD, on markers of bone remodeling and the safety profile will be evaluated as well. All subjects will receive a subcutaneous injection of Denosumab or placebo administered by a health care professional on days 0 and 180 (±3).
Investigators
Ersi Voskaridou
Director of National center of Thalassaemia and Haemoglobinopathies of Laikon General Hospital of Athens
Laikο General Hospital, Athens
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
Arms & Interventions
Denosumab
In Group A, 60 mg Denosumab will be administered sc, every 6 months for 12 months for a total of 2 doses (day 0 and day 180)
Intervention: Denosumab
Placebo
In Group B placebo will be administered sc, every 6 months for 12 months for a total of 2 doses (day 0 and day 180)
Intervention: Placebo
Outcomes
Primary Outcomes
The percent change in the lumbar spine BMD
Time Frame: 12 months
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 Outcomes
- The percent change in BMD of the total hip and femoral neck(12 months)
- The percent change in BMD at the distal third radius(12 months)
- The percent change in serum C-Termina Telopeptide (sCTX) at Month 3 post injection(3 months)