Contact information
Type
Scientific
Primary contact
Dr Francis H Glorieux
ORCID ID
Contact details
Shriners Hospitals for Children
1529 Cedar Avenue
Montreal
H3G 1A6
Canada
-
ncyr@shriners.mcgill.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00982124
Protocol/serial number
SCH-INFOI
Study information
Scientific title
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
Acronym
Study hypothesis
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.
Ethics approval
Faculty of Medicine, McGill University Institutional Review Board, 08/06/2009, ref: A06-M73-06A
Study design
International multicentre open-label efficacy and safety trial
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Osteogenesis imperfecta
Intervention
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.
Intervention type
Drug
Phase
Phase II
Drug names
Zoledronic acid
Primary outcome measures
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.
Secondary outcome measures
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.
Overall trial start date
01/10/2009
Overall trial end date
31/12/2012
Reason abandoned
Eligibility
Participant inclusion criteria
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.
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
20
Participant exclusion criteria
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
Recruitment start date
01/10/2009
Recruitment end date
31/12/2012
Locations
Countries of recruitment
Australia, Belgium, Brazil, Canada, Finland, France, South Africa, United Kingdom, United States of America
Trial participating centre
Shriners Hospitals for Children
Montreal
H3G 1A6
Canada
Sponsor information
Organisation
Novartis Pharmaceuticals (Canada)
Sponsor details
385
Boul. Bouchard
Dorval
Québec
Montreal
H9S 1A9
Canada
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Novartis Pharmaceuticals (Canada)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary