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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-000931-18 | EudraCT Number |
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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.
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:
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Denosumab | Active Comparator | 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) |
|
| Placebo | Placebo Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Denosumab | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| The percent change in the lumbar spine BMD | 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 | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| The percent change in BMD of the total hip and femoral neck | 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 | 12 months |
| The percent change in BMD at the distal third radius |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse event incidence by system organ class and preferred term | Seventeen cases of adverse events were reported. 14/17 were classified as mild(grade 1). 3/14 mild adverse eents concerned the placebo group. 11/14 of the mild adverse events concerned abnormalities of blood or biochemical testing. Only 3 of them had headache, diarrhea and fever. Three serious adverse events in denosumab group were pleural effusion(grade 3), supraventricular tachycardia(grade 4) and atrial fibrillation (grade3). These all three events were defined as unrelated to study drug. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ersi Voskaridou, Doctor | General Hospital of Athens "Laikon" | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| General Hospital of Athens "Laikon" | Athens | Attica | 11526 | Greece |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30381400 | Derived | Voskaridou E, Ntanasis-Stathopoulos I, Papaefstathiou A, Christoulas D, Dimopoulou M, Repa K, Papatheodorou A, Peppa M, Terpos E. Denosumab in transfusion-dependent thalassemia osteoporosis: a randomized, placebo-controlled, double-blind phase 2b clinical trial. Blood Adv. 2018 Nov 13;2(21):2837-2847. doi: 10.1182/bloodadvances.2018023085. |
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| ID | Term |
|---|---|
| D017086 | beta-Thalassemia |
| D010024 | Osteoporosis |
| ID | Term |
|---|---|
| D013789 | Thalassemia |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
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| ID | Term |
|---|---|
| D000069448 | Denosumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
|
| Placebo | Drug | 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. |
|
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 |
| 12 months |
| The percent change in serum C-Termina Telopeptide (sCTX) at Month 3 post injection | To evaluate the effect of Denosumab on markers of bone remodeling of patients with Thalassemia Major and Osteoporosis. | 3 months |
| 12 months |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | To evaluate the safety profile of Denosumab in patients with Thalassemia Major and Osteoporosis. Hematological parameters: Hemoglobin (Hb), White blood cell number (WBC) and platelets number Biochemical parameters: ALT U/L, AST U/L, Alkaline phosphatase IU/L, CPK IU/L, Calcium mg/dL, Creatinine mg/dL, Direct bilirubin mg/dL, LDH U/L, Phosphate mg/dL, Total bilirubin mg/dL, Total protein g/dL, Urea mg/dL, Uric acid mg/dL, albumin g/dL, ferritin ng/mL, glucose mg/dL, iron μg/dL, magnesium mg/dL, potassium mEq/L, sodium mEq/L, γGT IU/L. | 12 months |
| Changes in general appearance at each visit | General appearance of the patients will be assessed at each visit as "normal" of "affected". | 12 months |
| Changes in skin contour at each visit | At each visit all patients will be evaluated for potential changes in skin contour and will be classified as i) normal or pale and ii) icteric or non-icteric | 12 months |
| Changes in cardiology clinical examination at each visit | At each visit all patients will be evaluated for potential changes in heart clinical examination assessed by auscultation that will be classified as normal or abnormal | 12 months |
| Changes in ECG at each visit | At each visit all patients will be evaluated for ECG changes regarding the cardiac rhythm, the cardiac rate, the P Wave, the PR Interval, the QRS Complex, the QT Interval, and will be classified as normal or abnormal. | 12 months |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |