Condition category
Not Applicable
Date applied
23/09/2009
Date assigned
04/01/2010
Last edited
26/05/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.novartis.ca/

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

Publication citations

Additional files

Editorial Notes