OsteoporosisPhase 3NCT00799266
An Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids
A Phase 3 study testing Zoledronic acid in people with Osteoporosis, run by Novartis Pharmaceuticals at 12 sites in 6 countries.
Trial summary
This study was designed to evaluate the efficacy and safety of zoledronic acid compared to placebo in osteoporotic children treated with glucocorticoids Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Zoledronic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 12 sitesin 6 countries
- Study dates
- 4 Dec 2008to 5 Mar 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- A diagnosis of chronic rheumatologic conditions or inflammatory bowel disease or Duchenne muscular dystrophy requiring systemic glucocorticoids (i.v. or oral) within 12 months prior to screening
- Lumbar Spine BMDZ-score of -0.5 or worse
- Evidence of at least at least 1 vertebral compression fracture of Genant Grade 1 or higher (or radiographic signs of vertebral fracture) within 1 month from Screening visit OR One or more, low-trauma, lower extremity long-bone fracture which occurred sometime within the 2 years PRECEDING enrollment in the study OR Two or more, low-trauma, upper extremity long-bone fractures which occurred sometime within the 2 years PRECEDING enrollment in the study
- Consent/assent to study participation
Who cannot join
- History of primary bone disease (OI, Idiopathic Juvenile Osteoporosis, Rickets/Osteomalacia)
- Any medical condition that might have interfered with the evaluation of lumbar spine BMD, such as severe scoliosis or spinal fusion. Patients with less than 3 evaluable vertebrae by Dual Energy X-ray Absorptiometry (DXA) evaluation in the region of interest lumbar 1 (L1) to lumbar 4 (L4),
- Hypocalcemia and hypophosphatemia
- Serum 25-hydroxy vitamin D concentrations of <20 ng/mL or <50 nmol/L
- estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m2
- serum creatinine increase between Visit 1 and Visit 2 >0.5 mg/dL (44.2 μmol/L)
- Uncontrolled symptoms of cardiac failure or arrhythmia
- Any prior use of bisphosphonates, or high dose sodium fluoride
Trial locations and contacts
12 sites in 6 countries.
12 sites in 6 countries
Canada5 sites
Novartis Investigative Site
Montreal, Quebec, H3H 1P3
Novartis Investigative Site
Montreal, Quebec, H3T 1C5
Novartis Investigative Site
Ottawa, Ontario, K1H 8L1
Novartis Investigative Site
Vancouver, British Columbia, V6H 3V4
Novartis Investigative Site
Winnipeg, Manitoba, R3E 0Z2
Russia2 sites
Novartis Investigative Site
Moscow, 119991
Novartis Investigative Site
Saint Petersburg, 195067
United Kingdom2 sites
Novartis Investigative Site
Manchester, M14 0JH
Novartis Investigative Site
West Midlands, Birmingham, B4 6NH
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo Controlled Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly Compared to Placebo in Osteoporotic Children Treated With Glucocorticoids.
This study was designed to evaluate the efficacy and safety of zoledronic acid compared to placebo in osteoporotic children treated with glucocorticoids
Read the detailed description
In March 2017, Novartis stopped enrollment as the study was not feasible to be conducted due to low enrollment and other recruitment challenges. Patients receiving the treatment continued to receive the treatment per protocol.
- Conditions
- Osteoporosis
- Being tested
- Zoledronic acid, Placebo
- Keywords
- Osteoporosis, children and adolescents, zoledronic acid, chronic inflammation, Duchenne muscular dystrophy, glucocorticoids, chronic inflammatory conditions
- Medical subject headings
- Osteoporosis, Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic acidDrug
intravenous infusion
PlaceboDrug
intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Zoledronic acid | Experimental | Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid Receives: Drug: Zoledronic acid |
| Placebo | Placebo comparator | Twice yearly i.v of infusion of Placebo (similar dosing as active drug) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 12
Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 12. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition.
Measured: Month 12
Secondary outcomes (13)
Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 6
Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 6. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition.
Measured: Month 6
Mean Change From Baseline in Lumbar Spine BMC at Month 6 and 12
Lumbar Spine BMC was determined by the central imaging vendor before first treatment and at Months 6 and 12. The methods to be used to measure BMC were described in the respective DXA Manuals.
Measured: Month 6, Month 12
Mean Change From Baseline in Total Body BMC at Month 6 and 12
Total body BMC was all determined by the central imaging vendor before first treatment and at Months 6 and 12. The methods to be used to measure BMC were described in the respective DXA Manuals.
Measured: Month 6, Month 12
Mean Change From Baseline in Serum P1NP at Months 6 and 12
Serum Procollagen type 1 amino-terminal propeptide (P1NP) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.
Measured: Month 6, Month 12
Mean Change From Baseline in BSAP at Months 6 and 12
Bone specific alkaline phosphatase (BSAP) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.
Measured: Month 6, Month 12
Mean Change From Baseline in Serum NTX at Months 6 and 12
Serum Cross linked N-telopeptide (NTX) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.
Measured: Month 6, Month 12
Mean Change From Baseline in Serum TRAP-5b at Months 6 and 12
Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.
Measured: Month 6, Month 12
Number of Participants With New Vertebral Fractures at Month 12
New vertebral fractures were defined as fractures of Genant Grade 1 or higher that occurred at lumbar or thoracic spine from first dose infusion to the end of the study.
Measured: Month 12
Mean Change From Baseline in Vertebral Morphometry at Month 12
Vertebral morphometry (or concave index) was calculated using the average ratio between mid-height and posterior height from L1 to L4 and performed by a central reader.
Measured: Month 12
Percentage of Patients With Reduction in Pain at Months 3, 6, 9 and 12
Pain was evaluated at each visit (in office and telephone visit) at randomization, Months 3, 6, 9 and 12 using the Faces Pain Scale-Revised (FPS-R). Children were selecting the face that best fits their pain. The pain score ranged from 0 (No Pain) to 10 (Very Much Pain). The reduction in pain from baseline by visit was evaluated based on whether or not patients had a decrease in their FPS-R from baseline. If pain remained the same or worsened from baseline a patient was classified as '0' and if the pain scale decreased then the patient was classified as '1'.
Measured: Month 3, Month 6, Month 9 and Month 12
Mean Change From Baseline in 2nd Metacarpal Cortical Width at Month 12
Left posteroanterior (PA) hand/wrist X-ray were taken at Visit 1 and at the Month 12 visit to assess bone age and the between-treatment differences for change in 2nd metacarpal cortical width at Month 12 relative to baseline. If a fracture of the left upper extremity precluded radiographic imaging, then the right hand was evaluated for this purpose. In this case, the right hand was be imaged at both Visit 1 and at Month 12. The information was used in the assessment of bone density.
Measured: Month 12
Urinary Concentration of Zoledronic Acid at Month 12
Urine was collected overnight or for at least 4 waking hours from all patients able to provide specimens, to measure urinary concentration of zoledronic acid at Month 12. Only descriptive analysis done.
Measured: Month 12
Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids
Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that zoledronic acid is safe for the treatment of osteoporotic children treated with glucocorticoids through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis done.
Measured: Baseline through Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2008 (estimated)
- Study start4 Dec 2008
- Primary completion5 Mar 2018
- Study completion5 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00799266
- Sponsor's protocol ID
- CZOL446H2337
- Other IDs
- 2008-001252-52, 2008
- Status last verified
- Sep 2020
- First submitted
- 26 Nov 2008
- Last updated
- 2 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Publications
Ward LM, Choudhury A, Alos N, Cabral DA, Rodd C, Sbrocchi AM, Taback S, Padidela R, Shaw NJ, Hosszu E, Kostik M, Alexeeva E, Thandrayen K, Shenouda N, Jaremko JL, Sunkara G, Sayyed S, Aftring RP, Munns CF. Zoledronic Acid vs Placebo in Pediatric Glucocorticoid-induced Osteoporosis: A Randomized, Double-blind, Phase 3 Trial. J Clin Endocrinol Metab. 2021 Nov 19;106(12):e5222-e5235. doi: 10.1210/clinem/dgab458.
PubMed 34228102
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo Controlled Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly Compared to Placebo in Osteoporotic Children Treated With Glucocorticoids.
- ClinicalTrials.gov ID
- NCT00799266
- Acronym / sponsor ID
- CZOL446H2337
- Conditions
- Osteoporosis
- Keywords
- Osteoporosis, children and adolescents, zoledronic acid, chronic inflammation, Duchenne muscular dystrophy, glucocorticoids, chronic inflammatory conditions
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 4 Dec 2008 (actual)
- Primary completion
- 5 Mar 2018 (actual)
- Study completion
- 5 Mar 2018 (actual)
- First posted
- 27 Nov 2008 (estimated)
- Results
- Posted 5 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was designed to evaluate the efficacy and safety of zoledronic acid compared to placebo in osteoporotic children treated with glucocorticoids
Detailed description
In March 2017, Novartis stopped enrollment as the study was not feasible to be conducted due to low enrollment and other recruitment challenges. Patients receiving the treatment continued to receive the treatment per protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zoledronic acid | Experimental | Drug: Zoledronic acidTwice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid |
| Placebo | Placebo comparator | Drug: PlaceboTwice yearly i.v of infusion of Placebo (similar dosing as active drug) |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- A diagnosis of chronic rheumatologic conditions or inflammatory bowel disease or Duchenne muscular dystrophy requiring systemic glucocorticoids (i.v. or oral) within 12 months prior to screening
- Lumbar Spine BMDZ-score of -0.5 or worse
- Evidence of at least at least 1 vertebral compression fracture of Genant Grade 1 or higher (or radiographic signs of vertebral fracture) within 1 month from Screening visit OR One or more, low-trauma, lower extremity long-bone fracture which occurred sometime within the 2 years PRECEDING enrollment in the study OR Two or more, low-trauma, upper extremity long-bone fractures which occurred sometime within the 2 years PRECEDING enrollment in the study
- Consent/assent to study participation
Key exclusion criteria (8 listed)
- History of primary bone disease (OI, Idiopathic Juvenile Osteoporosis, Rickets/Osteomalacia)
- Any medical condition that might have interfered with the evaluation of lumbar spine BMD, such as severe scoliosis or spinal fusion. Patients with less than 3 evaluable vertebrae by Dual Energy X-ray Absorptiometry (DXA) evaluation in the region of interest lumbar 1 (L1) to lumbar 4 (L4),
- Hypocalcemia and hypophosphatemia
- Serum 25-hydroxy vitamin D concentrations of <20 ng/mL or <50 nmol/L
- estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m2
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 infusion | Drug | Zoledronic acid |
| Placebointravenous infusion | Drug | Placebo |
Primary outcome
Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 12
Time frame: Month 12
Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 12. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition.
13 secondary outcomes
Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 6
Time frame: Month 6
Mean Change From Baseline in Lumbar Spine BMC at Month 6 and 12
Time frame: Month 6, Month 12
Mean Change From Baseline in Total Body BMC at Month 6 and 12
Time frame: Month 6, Month 12
Mean Change From Baseline in Serum P1NP at Months 6 and 12
Time frame: Month 6, Month 12
Mean Change From Baseline in BSAP at Months 6 and 12
Time frame: Month 6, Month 12
Mean Change From Baseline in Serum NTX at Months 6 and 12
Time frame: Month 6, Month 12
Mean Change From Baseline in Serum TRAP-5b at Months 6 and 12
Time frame: Month 6, Month 12
Number of Participants With New Vertebral Fractures at Month 12
Time frame: Month 12
Mean Change From Baseline in Vertebral Morphometry at Month 12
Time frame: Month 12
Percentage of Patients With Reduction in Pain at Months 3, 6, 9 and 12
Time frame: Month 3, Month 6, Month 9 and Month 12
Mean Change From Baseline in 2nd Metacarpal Cortical Width at Month 12
Time frame: Month 12
Urinary Concentration of Zoledronic Acid at Month 12
Time frame: Month 12
Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids
Time frame: Baseline through Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34228102Ward LM, Choudhury A, Alos N, Cabral DA, Rodd C, Sbrocchi AM, Taback S, Padidela R, Shaw NJ, Hosszu E, Kostik M, Alexeeva E, Thandrayen K, Shenouda N, Jaremko JL, Sunkara G, Sayyed S, Aftring RP, Munns CF. Zoledronic Acid vs Placebo in Pediatric Glucocorticoid-induced Osteoporosis: A Randomized, Double-blind, Phase 3 Trial. J Clin Endocrinol Metab. 2021 Nov 19;106(12):e5222-e5235. doi: 10.1210/clinem/dgab458.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
12 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Zoledronic acid in people with Osteoporosis, run by Novartis Pharmaceuticals at 12 sites in 6 countries.
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 8 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 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Canada, Russia, United Kingdom, Australia, Hungary and 1 more country. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 12 (time frame: Month 12). 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 NCT00799266, 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 2 Sep 2020.