An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta (INFOI)

An International, Multicenter, Open-label, Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta

The investigators have currently finished conducting an international multi-center trial that compares the efficacy and safety of pamidronate and zoledronate in the treatment of moderate to severe forms of Osteogenesis Imperfecta (OI). This trial has included only children above one year of age. The aim of the current study is to extend the observations of that currently finished study to infants below 1 year of age. Moreover, it is possible to administer zoledronate in a single short infusion instead of the three-day cycles with Pamidronate, therefore decreasing patient and family burdens with shorter stays in the hospital.

Study Overview

• Status: Completed
• Conditions: Osteogenesis Imperfecta
• Intervention / Treatment: Drug: Zoledronic Acid

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A0A9
      • Shriners Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children, male or female 2 weeks to < 12 months of age, at least at 38 weeks gestational age.
• Any child with phenotypic OI type II, III or IV.
• Any child classified as OI type I, V-VIII that has had at least two or more previous fractures of long bone, or vertebral compression fractures, and a low bone mineral density.
• No previous treatment with bisphosphonates.
• Negative urine protein as measured by dipstick. One repeat assessment of the urine protein will be allowed.

Exclusion Criteria:

• Blood oxygen saturation of less than 90% in room air.
• Serum creatinine level greater than 56 µmol/L.
• Any clinically significant clinical laboratory abnormalities at screening.
• Treatment with any investigational drug within the past 30 days.
• Patients who are unlikely to be able to complete the study or comply with the visit schedule.
• Any disease or planned therapy which will interfere with the procedures or data collection of this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm (only); Zoledronic acid infusion	Drug: Zoledronic Acid; Each patient is to receive an initial dose of zoledronic acid of 0.0125 mg per kg body weight, then subsequent doses of zoledronic acid at a dose of 0.025 mg per kg body weight once every 12 to 13 weeks for 104 weeks (total of 8 doses).; Other Names: Aclasta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary objective of this trial is to assess the change in lumbar spine bone mineral density Z-score at month 24 relative to baseline in zoledronic acid treated infants compared to historical controls.	3 times during 10 visits within 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the effect of zoledronic acid on the number of clinical fractures &/or vertebral compressions that occur over a two year period compared to untreated historical controls in infants.	3 times during 10 visits within 2 years

Collaborators and Investigators

• Sponsor: Shriners Hospitals for Children
• Collaborators: Novartis
• Investigators: Principal Investigator: Francis H. Glorieux, MD, PhD, McGill University

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: September 21, 2009
• First Submitted That Met QC Criteria: September 21, 2009
• First Posted (Estimate): September 22, 2009

Study Record Updates

• Last Update Posted (Estimate): April 19, 2016
• Last Update Submitted That Met QC Criteria: April 18, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Osteogenesis Imperfecta; Infants with moderate to severe Osteogenesis Imperfecta
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Bone Diseases, Developmental; Osteochondrodysplasias; Collagen Diseases; Osteogenesis Imperfecta; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: SHC-INFOI; IRB - A06-M73-06A; Health Canada - 9427-S1926-24C