Thalassemia MajorPhase 2NCT02559648
Denosumab vs Placebo in Patients With Thalassemia Major and Osteoporosis
A Phase 2 study testing Denosumab in people with Thalassemia Major and Osteoporosis, run by Ersi Voskaridou at 1 site in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Thalassemia Major, Osteoporosis
- What is being tested?
- Denosumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteGreece
- Study dates
- Sep 2014to Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
- 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 malabsorption including Celiac disease, Short Bowel Syndrome, Crohn's disease, Previous Gastric Bypass.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Efficacy of Denosumab in Patients With Thalassemia Major and Osteoporosis: A Randomized, Placebo-controlled, Single-site, Double Blind Phase 2b Clinical Trial
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.
Read the 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).
- Conditions
- Thalassemia Major, Osteoporosis
- Being tested
- Denosumab, Placebo
- Medical subject headings
- beta-Thalassemia, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called Prolia
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (3)
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
Measured: 12 months
The percent change in BMD at the distal third radius
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
Measured: 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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2015 (estimated)
- Study startSep 2014
- Primary completionDec 2016
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thalassemia MajorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ersi Voskaridou
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ersi Voskaridou, Laikο General Hospital, Athens
- Investigators
- Ersi Voskaridou, Doctor, Principal investigator, General Hospital of Athens "Laikon"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02559648
- Sponsor's protocol ID
- EL-THOS-001
- Other IDs
- 2014-000931-18, 2014
- Status last verified
- Aug 2019
- First submitted
- 23 Sep 2015
- Last updated
- 26 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 30381400
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Efficacy of Denosumab in Patients With Thalassemia Major and Osteoporosis: A Randomized, Placebo-controlled, Single-site, Double Blind Phase 2b Clinical Trial
- ClinicalTrials.gov ID
- NCT02559648
- Acronym / sponsor ID
- EL-THOS-001
- Conditions
- Thalassemia Major, Osteoporosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Ersi VoskaridouUniversity, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 24 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab | Active comparator | Drug: DenosumabIn 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 | Drug: PlaceboIn Group B placebo will be administered sc, every 6 months for 12 months for a total of 2 doses (day 0 and day 180) |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: ProliaPatients 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. | Drug | Denosumab |
| PlaceboPatients 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. | Drug | Placebo |
Primary outcome
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
3 secondary outcomes
The percent change in BMD of the total hip and femoral neck
Time frame: 12 months
The percent change in BMD at the distal third radius
Time frame: 12 months
The percent change in serum C-Termina Telopeptide (sCTX) at Month 3 post injection
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2019.
- Derived from this study: PubMed 30381400Voskaridou 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ersi Voskaridou, Doctor principal investigator
General Hospital of Athens "Laikon"
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denosumab in people with Thalassemia Major and Osteoporosis, run by Ersi Voskaridou at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The percent change in the lumbar spine BMD (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02559648, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2019.