An efficacy and safety trial of intravenous zoledronic acid in infants less than one year of age, with severe osteogenesis imperfecta

ISRCTN	ISRCTN95879580
DOI	https://doi.org/10.1186/ISRCTN95879580
ClinicalTrials.gov number	NCT00982124
Secondary identifying numbers	SCH-INFOI

Submission date: 23/09/2009
Registration date: 04/01/2010
Last edited: 10/05/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Other

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Francis H Glorieux
Scientific

Shriners Hospitals for Children
1529 Cedar Avenue
Montreal
H3G 1A6
Canada

Email	ncyr@shriners.mcgill.ca

Study information

Study design	International multicentre open-label efficacy and safety trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
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
Study objectives	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.
Ethics approval(s)	Faculty of Medicine, McGill University Institutional Review Board, 08/06/2009, ref: A06-M73-06A
Health condition(s) or problem(s) studied	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. 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.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Zoledronic acid
Primary outcome measure	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 study start date	01/10/2009
Completion date	31/12/2012

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	2 Weeks
Upper age limit	12 Months
Sex	Both
Target number of participants	20
Key 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
Key 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
Date of first enrolment	01/10/2009
Date of final enrolment	31/12/2012

Locations

Countries of recruitment

Australia
Belgium
Brazil
Canada
Finland
France
South Africa
United Kingdom
United States of America

Study participating centre

Shriners Hospitals for Children

Montreal
H3G 1A6
Canada

Sponsor information

Novartis Pharmaceuticals (Canada)
Industry

385, Boul. Bouchard
Dorval, Québec
Montreal
H9S 1A9
Canada

Website	http://www.novartis.ca/
"ROR"	https://ror.org/05afs3z13

Funders

Funder type

Industry

Novartis Pharmaceuticals Canada
Private sector organisation / For-profit companies (industry)

Alternative name(s): Novartis Canada
Location: Canada

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

10/05/2019: No publications found. Verifying results with principal investigator.
02/10/2017: No publications found, verifying study status with principal investigator.