Denosumab Versus Zoledronic Acid in Thalassemia-Induced Osteoporosis

NCT03040765 | Terminated Phase 3 DMC

• 1 other identifier: 16441/16
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to compare the two medications Denosumab and Zoledronic Acid For Patients With Beta Thalassemia Major Induced Osteoporosis. Patients with B-thalassemia major induce osteoporosis will undergo baseline assessment of the bone densitometry by Dual-energy X-ray absorptiometry scan as a standard of care by the radiology department, then a blood test for bone specific Alkaline phosphatase and type-1 Carboxy Telopeptide will be measured by the chemistry lab. Patients with B-Thalassemia Major induced osteoporosis, who are 18 years of age or more and willing to participate in the study will be enrolled after consenting by the primary investigator in hematology outpatient clinic. Patients with osteoporosis will receive one of the two medications, at the end of the year Dual-energy X-ray absorptiometry scan will be done to compare the response of the two medications. The potential risks include the drug-related side effects

Conditions

Thalassemia Majors (Beta-Thalassemia Major); Osteoporosis

Keywords

Osteoporosis; Beta-Thalassemia Major; Denosumab; Zoledronic Acid

Outcome Measures

Primary Outcomes (1)

• Number of patients with a 50 percent or greater reduction in type-1 collagen carboxy telopeptide from the baseline

  Number of patients with a 50 percent or greater reduction in type-1 collagen carboxy telopeptide from the baseline

  12 months

Secondary Outcomes (2)

• Number of patients with a 50 percent or greater improvement in Dual-energy X-ray absorptiometry scan from the baseline

  12 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  12 months

Study Arms (2)

Denosumab

ACTIVE COMPARATOR

Denosumab 60 MG/ML Prefilled Syringe Denosumab Dose: 60 milligrams, subcutaneous injection, every 6 months (twice a year)

Drug: Denosumab 60 MG/ML Prefilled Syringe

Zoledronic Acid

ACTIVE COMPARATOR

Zoledronic Acid 5Mg/Bag 100Ml Inj Zoledronic acid will be 5 milligrams, Intravenous injection, once a year

Drug: Zoledronic Acid 5Mg/Bag 100Ml Inj

Interventions

Denosumab 60 MG/ML Prefilled Syringe DRUG

Denosumab 60 MG/ML will be administered to 20 patients with b-thalassemia major

Also known as: Prolia

Denosumab

Zoledronic Acid 5Mg/Bag 100Ml Inj DRUG

Zoledronic Acid 5Mg/Bag 100Ml Inj will be administered to 20 patients with b-thalassemia major

Also known as: Aclasta

Zoledronic Acid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to participate in the study
• Age 18 years old or older
• Eastern Cooperative Oncology Group Performance Status less than or equal 2

You may not qualify if:

• Age less than 18 years old
• Not willing to participate in the study
• Vulnerable subjects or Eastern Cooperative Oncology Group Performance Status 3 or 4

Sponsors & Collaborators

• Hamad Medical Corporation: lead

Study Sites (1)

National Center for Cancer Care & Research (NCCCR)

Doha, Qatar

Location

Related Publications (21)

• Baldini M, Forti S, Marcon A, Ulivieri FM, Orsatti A, Tampieri B, Airaghi L, Zanaboni L, Cappellini MD. Endocrine and bone disease in appropriately treated adult patients with beta-thalassemia major. Ann Hematol. 2010 Dec;89(12):1207-13. doi: 10.1007/s00277-010-1007-0. Epub 2010 Jun 26.

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• Scacchi M, Danesi L, Cattaneo A, Valassi E, Pecori Giraldi F, Argento C, D'Angelo E, Mirra N, Carnelli V, Zanaboni L, Tampieri B, Cappellini MD, Cavagnini F. Bone demineralization in adult thalassaemic patients: contribution of GH and IGF-I at different skeletal sites. Clin Endocrinol (Oxf). 2008 Aug;69(2):202-7. doi: 10.1111/j.1365-2265.2008.03191.x. Epub 2008 Jan 21.

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• Voskaridou E, Terpos E. Pathogenesis and management of osteoporosis in thalassemia. Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:86-93.

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• Pietrapertosa AC, Minenna G, Colella SM, Santeramo TM, Renni R, D'Amore M. Osteoprotegerin and RANKL in the pathogenesis of osteoporosis in patients with thalassaemia major. Panminerva Med. 2009 Mar;51(1):17-23.

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• Mahachoklertwattana P, Pootrakul P, Chuansumrit A, Choubtum L, Sriphrapradang A, Sirisriro R, Rajatanavin R. Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes. J Bone Miner Metab. 2006;24(2):146-52. doi: 10.1007/s00774-005-0661-0.

  PMID: 16502122 BACKGROUND

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  PMID: 21798385 BACKGROUND

• Skordis N, Ioannou YS, Kyriakou A, Savva SC, Efstathiou E, Savvides I, Christou S. Effect of bisphosphonate treatment on bone mineral density in patients with thalassaemia major. Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:144-8.

  PMID: 19337169 BACKGROUND

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  PMID: 9591744 BACKGROUND

• Mahachoklertwattana P, Chuansumrit A, Sirisriro R, Choubtum L, Sriphrapradang A, Rajatanavin R. Bone mineral density, biochemical and hormonal profiles in suboptimally treated children and adolescents with beta-thalassaemia disease. Clin Endocrinol (Oxf). 2003 Mar;58(3):273-9. doi: 10.1046/j.1365-2265.2003.01707.x.

  PMID: 12608931 BACKGROUND

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• Michael H, Harkonen PL, Vaananen HK, Hentunen TA. Estrogen and testosterone use different cellular pathways to inhibit osteoclastogenesis and bone resorption. J Bone Miner Res. 2005 Dec;20(12):2224-32. doi: 10.1359/JBMR.050803. Epub 2005 Aug 1.

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• Gorny G, Shaw A, Oursler MJ. IL-6, LIF, and TNF-alpha regulation of GM-CSF inhibition of osteoclastogenesis in vitro. Exp Cell Res. 2004 Mar 10;294(1):149-58. doi: 10.1016/j.yexcr.2003.11.009.

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MeSH Terms

Conditions

beta-Thalassemia; Osteoporosis

Interventions

Denosumab; Zoledronic Acid

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mohamed Yassin

  Hamad Medical Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2017
• First Posted: February 2, 2017
• Study Start: May 14, 2018
• Primary Completion: April 8, 2019
• Study Completion: April 8, 2019
• Last Updated: December 12, 2019

Record last verified: 2018-05

Locations

QA (1)