Denosumab vs Placebo in Patients With Thalassemia Major and Osteoporosis

NCT02559648 | Completed Phase 2

• 2 other identifiers: EL-THOS-0012014-000931-18
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Thalassemia Major; Osteoporosis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• 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

Other Outcomes (6)

• Adverse event incidence by system organ class and preferred term

  12 months

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

  12 months

• Changes in general appearance at each visit

  12 months

Study Arms (2)

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)

Drug: Denosumab

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)

Drug: Placebo

Interventions

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.

Also known as: Prolia

Denosumab

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.

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ersi Voskaridou: lead

Study Sites (1)

General Hospital of Athens "Laikon"

Athens, Attica, 11526, Greece

Location

Related Publications (1)

• 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.

  PMID: 30381400 DERIVED

MeSH Terms

Conditions

beta-Thalassemia; Osteoporosis

Interventions

Denosumab

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

Study Officials

• Ersi Voskaridou, Doctor

  General Hospital of Athens "Laikon"

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of National center of Thalassaemia and Haemoglobinopathies of Laikon General Hospital of Athens

Study Record Dates

• First Submitted: September 23, 2015
• First Posted: September 24, 2015
• Study Start: September 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2017
• Last Updated: August 26, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)