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ISRCTN
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ISRCTN95879580
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ClinicalTrials.gov identifier
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NCT00982124
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Public title
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An efficacy and safety trial of intravenous zoledronic acid in infants less than one year of age, with severe osteogenesis imperfecta
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Scientific title
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An international, multicentre, open-label, efficacy and safety trial of intravenous zoledronic acid in infants less than one year of age, with severe osteogenesis imperfecta
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Acronym
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N/A
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Serial number at source
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SCH-INFOI
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Study hypothesis
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This is an international, multicentre, open-label efficacy and safety trial. The primary objective is to evaluate the change in lumbar spine bone mineral density Z-score at month 24 relative to baseline using intravenous zoledronic acid compared to untreated historical controls in infants with severe osteogenensis imperfecta, who are between 2 weeks and 1 year of age, all inclusive. The dose is weight dependent, which is described in detail below. All patients will receive an initial infusion of zoledronic acid at 0.0125 mg per kg body weight, followed by infusions of zoledronic acid given every three months at a dose of 0.025 mg per kg body weight, administered as a 30 to 45-minute infusion. There will be a total of 10 visits over the 24 month period of time for all patients. The total number of doses is 8. All zoledronic acid patients will be hospitalised for 48 hours at the first administration of zoledronic acid to monitor for drug reactions. Ionised calcium will be measured pre-dose, 12 hours, 24, 36 and 48 hours post-dose during the hospitalisation period. Sites will call all patients at scheduled monthly visits for determination of adverse events and concomitant medications throughout the study, except for those months where there is a scheduled on-site visit. Dual energy x-ray absorptiometry (DXA) measurements of the lumbar spine and total body and radiological skeletal survey will be done at screening or at first administration of zoledronic acid, the 12 month visit (visit 6) and final visit (visit 10). Twenty infants will be enrolled; enrolment will be competitive.
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Lay summary
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Ethics approval
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Faculty of Medicine, McGill University Institutional Review Board approved on the 8th June 2009 (ref: A06-M73-06A)
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Study design
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International multicentre open-label efficacy and safety trial
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Countries of recruitment
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Australia, Belgium, Brazil, Canada, Finland, France, South Africa, United Kingdom, United States of America
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Disease/condition/study domain
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Osteogenesis imperfecta
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Participants - inclusion criteria
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1. Children, male or female, 2 weeks to less than 12 months of age, at least at 38 weeks gestational age
2. Any child with phenotypic OI type II, III or IV
3. No previous treatment with bisphosphonates
4. Negative urine protein as measured by dipstick. One repeat assessment of the urine protein will be allowed. The assessment will be make 2 weeks after the first assessment and the sample must be a urine collection after a 4-hour fast.
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Participants - exclusion criteria
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1. Blood oxygen saturation of less than 90% in room air
2. Serum creatinine level greater than 56 µmol/L
3. Any clinically significant clinical laboratory abnormalities at screening
4. Treatment with any investigational drug within the past 30 days
5. Patients who are unlikely to be able to complete the study or comply with the visit schedule
6. Any disease or planned therapy which will interfere with the procedures or data collection of this trial
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Anticipated start date
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01/10/2009
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Anticipated end date
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31/12/2012
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Status of trial
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Ongoing |
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Patient information material
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Not available in web format, please use the contact details below to request a patient information sheet
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Target number of participants
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20
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Interventions
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All patients will receive an initial infusion of zoledronic acid at 0.0125 mg per kg body weight, followed by infusions of zoledronic acid given every three months at a dose of 0.025 mg per kg body weight, administered as a 30 to 45-minute infusion. There will be a total of 10 visits over the 24 month period of time for all patients. The total number of doses is 8. All zoledronic acid patients will be hospitalised for 48 hours at the first administration of zoledronic acid to monitor for drug reactions. Ionised calcium will be measure pre-dose, 12 hours, 24, 36 and 48 hours post-dose during the hospitalisation period. Sites will call all patients at scheduled monthly visits for determination of adverse events and concomitant medications throughout the study, except for those months where there is a scheduled on-site visit. DXA measurements of the lumbar spine and total body and radiological skeletal survey will be done at screening or at first administration of zoledronic acid, the 12 month visit (visit 6) and final visit (visit 10). Twenty infants will be enrolled.
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Primary outcome measure(s)
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Change in lumbar spine bone mineral density Z-score at month 24 relative to baseline in zoledronic acid treated infants with severe osteogenesis imperfecta aged between 2 weeks to 1 year of age at entry, compared to historical controls. The efficacy of zoledronic acid will be demonstrated if it is shown to be a gain in Z-score of at least 1.
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Secondary outcome measure(s)
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Effect of zoledronic acid on the change in whole body bone mineral content after 12 and 24 months of treatment relative to baseline compared to historical controls in infants 2 weeks to 1 year of age.
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Sources of funding
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Novartis Pharmaceuticals (Canada)
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Trial website
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Publications
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Contact name
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Dr
Francis H
Glorieux
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Address
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1529 Cedar Avenue
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City/town
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Montreal
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Zip/Postcode
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H3G 1A6
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Country
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Canada
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Email
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ncyr@shriners.mcgill.ca
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Sponsor
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Novartis Pharmaceuticals (Canada)
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Address
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385, Boul. Bouchard
Dorval, Québec
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City/town
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Montreal
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Zip/Postcode
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H9S 1A9
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Country
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Canada
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Sponsor website:
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http://www.novartis.ca/
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Date applied
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23/09/2009
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Last edited
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04/01/2010
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Date ISRCTN assigned
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04/01/2010
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