Denosumab for the Treatment of Osteoporosis in Children: A Pilot Study

June 22, 2020 updated by: Dr. Leanne Ward, Children's Hospital of Eastern Ontario

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children'S Hospital Of Eastern Ontario

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

4 years to 16 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Subject or subject's legally acceptable representative has provided informed consent.
  2. Children aged 4 to 16 years at the time of enrolment.

  3. 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:

    1. 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
    2. 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
    3. 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.

Exclusion Criteria:

  1. Any child for whom the treating physician feels participation is not advised.
  2. Prior treatment with an osteoporosis agent (e.g. bisphosphonate).
  3. Renal insufficiency defined as an eGFR less than 60ml/min/1.73m2.
  4. Active or prior diagnosis of malignancy or undergoing investigations for a suspected childhood cancer.
  5. Currently breastfeeding or plans to breastfeed during the study.
  6. Pregnancy (verified by pre-treatment pregnancy test in all menstruating or sexually active females).
  7. Untreated vitamin D deficiency, defined as a serum 25OHD level <50nmol/L.
  8. Untreated hypocalcemia, defined as a serum ionized calcium level <1.1mmol/L.
  9. Active or historic eczema/cellulitis.
  10. Children planning dental procedures and/or dental surgery during the course of the study.
  11. Children with a documented history of atrial fibrillation.
  12. Children with asthma who are acetylsalicylic acid (ASA) sensitive.
  13. Children that have had parathyroid or thyroid surgery.
  14. Children who are allergic to rubber or latex.
  15. Males with a pregnant partner.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: Zoledronic Acid
Intravenous zoledronic acid 0.025mg/kg
Drug: Zoledronic Acid
Intravenous zoledronic acid 0.025mg/kg at baseline, 6 months, 12 months and 18 months
EXPERIMENTAL: Denosumab
Subcutaneous denosumab 1.0mg/kg
Drug: Denosumab
Subcutaneous denosumab 1.0mg/kg at baseline, 6 months, 12 months and 18 months

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
48 hours after each drug administration (48 hours post baseline and 48 hours post 6, 12 and 18 month visits)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital of Eastern Ontario

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 3, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 3, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 15, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2015

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 17, 2015

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 23, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 22, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DZA9DEC2015

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

No current plan

IPD Sharing Time Frame

No time frame

IPD Sharing Access Criteria

Access has not been made available

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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