OsteoporosisPhase 2NCT02632916
Denosumab for the Treatment of Osteoporosis in Children: A Pilot Study
A Phase 2 study testing Zoledronic Acid and Denosumab in people with Osteoporosis, run by Children's Hospital of Eastern Ontario at 1 site in Canada.
Trial summary
The aim of this study is to acquire preliminary, pilot data over a 2-year period on the safety and efficacy of subcutaneous denosumab versus the current CHEO standard-of-care (intravenous zoledronic acid) for the treatment of osteoporosis in children. Read more about this study
- Who is it for?
- Ages 4 to 16 years
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Zoledronic Acid and Denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2016to 3 Feb 2020
- 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 4 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Subject or subject's legally acceptable representative has provided informed consent.
- Children aged 4 to 16 years at the time of enrolment.
- Children with a history of clinically significant bone fragility in the preceding 24 months, requiring the child to have ONE or more of the following clinical profiles:
- At least one low-trauma vertebral or long bone fracture in a child with an underlying disease known to be associated with osteoporotic fractures (e.g. glucocorticoid-treated diseases, Crohn's disease, rheumatic disorders, Duchenne muscular dystrophy, other muscular dystrophies, spinal muscular atrophy, cerebral palsy); OR
- At least one low-trauma vertebral or long bone fracture in the last 24 months, in a child with a known genetic osteoporotic condition such as osteogenesis imperfecta (confirmed on molecular genetic testing); OR
- At least one low-trauma vertebral or long bone fracture in the last 24 months, in an otherwise healthy child with a diagnosis of osteoporosis confirmed on trans-iliac bone biopsy. Trans-iliac bone biopsy is a requirement in this sub-group as per the usual standard of care, as this is the only test that will definitively confirm osteoporosis in an otherwise healthy child who does not have a genetic bone fragility condition.
Who cannot join
- Any child for whom the treating physician feels participation is not advised.
- Prior treatment with an osteoporosis agent (e.g. bisphosphonate).
- Renal insufficiency defined as an eGFR less than 60ml/min/1.73m2.
- Active or prior diagnosis of malignancy or undergoing investigations for a suspected childhood cancer.
- Currently breastfeeding or plans to breastfeed during the study.
- Pregnancy (verified by pre-treatment pregnancy test in all menstruating or sexually active females).
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- Untreated vitamin D deficiency, defined as a serum 25OHD level <50nmol/L.
- Untreated hypocalcemia, defined as a serum ionized calcium level <1.1mmol/L.
- Active or historic eczema/cellulitis.
- Children planning dental procedures and/or dental surgery during the course of the study.
- Children with a documented history of atrial fibrillation.
- Children with asthma who are acetylsalicylic acid (ASA) sensitive.
- Children that have had parathyroid or thyroid surgery.
- Children who are allergic to rubber or latex.
- Males with a pregnant partner.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-Blinded, Randomized, Controlled, Phase 2 Pilot Study to Evaluate the Safety and Efficacy of Denosumab Compared to Zoledronic Acid for the Treatment of Osteoporosis in Children
The aim of this study is to acquire preliminary, pilot data over a 2-year period on the safety and efficacy of subcutaneous denosumab versus the current CHEO standard-of-care (intravenous zoledronic acid) for the treatment of osteoporosis in children. Both denosumab (1.0mg/kg) and zoledronic acid (0.025mg/kg) will be given as four doses separated by a six month interval (i.e. at baseline, 6 months, 12 months and 18 months), with follow-up to 2 years.
Read the detailed description
Bone fractures without significant trauma (also known as osteoporosis) are a frequent complication of chronic childhood diseases (for example, Duchenne muscular dystrophy and inflammatory disorders) and genetic disorders (such as osteogenesis imperfecta). To date, the only effective therapy for the treatment of osteoporosis in children is a class of medications known as bisphosphonates (which include pamidronate and zoledronic acid). Unfortunately, these medications have the disadvantage of frequent side effects with the first dose (including fever, nausea, vomiting and bone pain), as well as intravenous administration (delivery through a vein, similar to a bloodtest). Recently, a new medication has been proven effective in the treatment of adults with osteoporosis - this medication is called denosumab, and it has a distinct advantage over intravenous bisphosphonates since it is administered sub-cutaneously (through a small needle injected into the skin), plus an excellent safety profile. To date, denosumab has been used with success in a few children with rare forms of osteoporosis and other bone disorders. The purpose of this study is to further test the safety and benefits of denosumab in children with fractures due to osteoporosis, by comparing this new agent to the current standard treatment at CHEO, zoledronic acid. This will be a one year, pilot study in 20 children with a variety of forms of osteoporosis. Children enrolled in the study will be randomly assigned to receive zoledronic acid or denosumab every 6 months (for two doses), with tests carried out every few months over the course of the year to study the effects of these therapies on fractures, bone density and various safety parameters as measured by bloodtests. Overall, the results of this study will provide us with important information on the potential for denosumab to provide children with a safe, effective and convenient new osteoporosis treatment.
- Conditions
- Osteoporosis
- Being tested
- Zoledronic Acid, Denosumab
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic AcidDrug
Intravenous zoledronic acid 0.025mg/kg at baseline, 6 months, 12 months and 18 months
DenosumabDrug
Subcutaneous denosumab 1.0mg/kg at baseline, 6 months, 12 months and 18 months
| Study group | Role | What they receive |
|---|---|---|
| Zoledronic Acid | Active comparator | Intravenous zoledronic acid 0.025mg/kg Receives: Drug: Zoledronic Acid |
| Denosumab | Experimental | Subcutaneous denosumab 1.0mg/kg Receives: Drug: Denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The changes in serum ionized calcium levels at 48 hours following the administration of denosumab versus zoledronic acid.
To observe the changes in serum ionized calcium levels at 48 hours following the administration of denosumab versus zoledronic acid. Hypocalcemia at 48 hours has been chosen as the primary outcome since this is a clinically important side effect of both denosumab and zoledronic acid, and 48 hours is around the time of the anticipated calcium nadir
Measured: 48 hours after each drug administration (48 hours post baseline and 48 hours post 6, 12 and 18 month visits)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2015 (estimated)
- Study startAug 2016
- Primary completion3 Feb 2020
- Study completion3 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoporosisStudies 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Eastern Ontario
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Leanne Ward, Children's Hospital of Eastern Ontario
- Investigators
- Leanne Ward, MD, Principal investigator, Children's Hospital of Eastern Ontario
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02632916
- Sponsor's protocol ID
- DZA9DEC2015
- Status last verified
- Jun 2020
- First submitted
- 15 Dec 2015
- Last updated
- 23 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: No current plan
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Blinded, Randomized, Controlled, Phase 2 Pilot Study to Evaluate the Safety and Efficacy of Denosumab Compared to Zoledronic Acid for the Treatment of Osteoporosis in Children
- ClinicalTrials.gov ID
- NCT02632916
- Acronym / sponsor ID
- DZA9DEC2015
- Conditions
- Osteoporosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Children's Hospital of Eastern OntarioUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- 3 Feb 2020 (actual)
- Study completion
- 3 Feb 2020 (actual)
- First posted
- 17 Dec 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.
The aim of this study is to acquire preliminary, pilot data over a 2-year period on the safety and efficacy of subcutaneous denosumab versus the current CHEO standard-of-care (intravenous zoledronic acid) for the treatment of osteoporosis in children. Both denosumab (1.0mg/kg) and zoledronic acid (0.025mg/kg) will be given as four doses separated by a six month interval (i.e. at baseline, 6 months, 12 months and 18 months), with follow-up to 2 years.
Detailed description
Bone fractures without significant trauma (also known as osteoporosis) are a frequent complication of chronic childhood diseases (for example, Duchenne muscular dystrophy and inflammatory disorders) and genetic disorders (such as osteogenesis imperfecta). To date, the only effective therapy for the treatment of osteoporosis in children is a class of medications known as bisphosphonates (which include pamidronate and zoledronic acid). Unfortunately, these medications have the disadvantage of frequent side effects with the first dose (including fever, nausea, vomiting and bone pain), as well as intravenous administration (delivery through a vein, similar to a bloodtest). Recently, a new medication has been proven effective in the treatment of adults with osteoporosis - this medication is called denosumab, and it has a distinct advantage over intravenous bisphosphonates since it is administered sub-cutaneously (through a small needle injected into the skin), plus an excellent safety profile. To date, denosumab has been used with success in a few children with rare forms of osteoporosis and other bone disorders. The purpose of this study is to further test the safety and benefits of denosumab in children with fractures due to osteoporosis, by comparing this new agent to the current standard treatment at CHEO, zoledronic acid. This will be a one year, pilot study in 20 children with a variety of forms of osteoporosis. Children enrolled in the study will be randomly assigned to receive zoledronic acid or denosumab every 6 months (for two doses), with tests carried out every few months over the course of the year to study the effects of these therapies on fractures, bone density and various safety parameters as measured by bloodtests. Overall, the results of this study will provide us with important information on the potential for denosumab to provide children with a safe, effective and convenient new osteoporosis treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zoledronic Acid | Active comparator | Drug: Zoledronic AcidIntravenous zoledronic acid 0.025mg/kg |
| Denosumab | Experimental | Drug: DenosumabSubcutaneous denosumab 1.0mg/kg |
Who may qualify
- Ages
- 4 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Subject or subject's legally acceptable representative has provided informed consent.
- Children aged 4 to 16 years at the time of enrolment.
- Children with a history of clinically significant bone fragility in the preceding 24 months, requiring the child to have ONE or more of the following clinical profiles:
Key exclusion criteria (15 listed)
- Any child for whom the treating physician feels participation is not advised.
- Prior treatment with an osteoporosis agent (e.g. bisphosphonate).
- Renal insufficiency defined as an eGFR less than 60ml/min/1.73m2.
- Active or prior diagnosis of malignancy or undergoing investigations for a suspected childhood cancer.
- Currently breastfeeding or plans to breastfeed during the study.
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 |
|---|---|---|
| Zoledronic AcidIntravenous zoledronic acid 0.025mg/kg at baseline, 6 months, 12 months and 18 months | Drug | Zoledronic Acid |
| DenosumabSubcutaneous denosumab 1.0mg/kg at baseline, 6 months, 12 months and 18 months | Drug | Denosumab |
Primary outcome
The changes in serum ionized calcium levels at 48 hours following the administration of denosumab versus zoledronic acid.
Time frame: 48 hours after each drug administration (48 hours post baseline and 48 hours post 6, 12 and 18 month visits)
To observe the changes in serum ionized calcium levels at 48 hours following the administration of denosumab versus zoledronic acid. Hypocalcemia at 48 hours has been chosen as the primary outcome since this is a clinically important side effect of both denosumab and zoledronic acid, and 48 hours is around the time of the anticipated calcium nadir
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 23 Jun 2020.
- Individual participant dataSharing planned: Yes. No current plan
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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.
Leanne Ward, MD principal investigator
Children's Hospital of Eastern Ontario
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 Zoledronic Acid and Denosumab in people with Osteoporosis, run by Children's Hospital of Eastern Ontario at 1 site in Canada.
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 6 inclusion and 15 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 23 Jun 2020. 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 Canada. 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. 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 changes in serum ionized calcium levels at 48 hours following the administration of denosumab versus zoledronic acid. (time frame: 48 hours after each drug administration (48 hours post baseline and 48 hours post 6, 12 and 18 month visits)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jun 2020.