An international, multicenter, randomized, open-label, safety and efficacy trial of intravenous zoledronic acid administered either once or twice yearly in children with severe osteogenesis imperfecta, a 1-year extension to CZOL446H2202 - 2202E

• Register: EUCTR
• Last refreshed on: 1 May 2012
• Main ID: EUCTR2004-001666-40-HU
• Date of registration: 25/11/2004
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: An international, multicenter, randomized, open-label, safety and efficacy trial of intravenous zoledronic acid administered either once or twice yearly in children with severe osteogenesis imperfecta, a 1-year extension to CZOL446H2202 - 2202E
• Scientific title: An international, multicenter, randomized, open-label, safety and efficacy trial of intravenous zoledronic acid administered either once or twice yearly in children with severe osteogenesis imperfecta, a 1-year extension to CZOL446H2202 - 2202E
• Date of first enrolment: 01/02/2005
• Target sample size: 130
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-001666-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Hungary, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Children, male or female, between 1 year and 17 years of age at visit 1 of the extension, all inclusive, who have completed 1 year treatment of zoledronic acid or pamidronate in CZOL446H2202 trial.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Any disease or planned therapy which will interfere with the procedures or data collection of this trial.
• Any disease or abnormality that would prevent accurate bone-mineral density measurements of the lumbar spine (e.g., intra-abdominal calcification that may prohibit accurate data collection/interpretation; severe scoliosis, kyphosis, or metal implants, etc.)
• Any surgical bone-lengthening procedure, e.g. Ilizarov procedure planned/scheduled to occur during the trial.
• Female patients of child-bearing potential are eligible only if they are: not pregnant (serum ß-hCG pregnancy-test negative)/non-lactating; are sexually abstinent or are surgically sterile (tubal ligation or hysterectomy): and if sexually active, must be practicing a medically acceptable form of birth control, defined as the use of an IUD, a barrier method with spermicide, condoms, subdermal implant or oral contraceptives. Females of child-bearing potential who are sexually active must agree to continue to practice their birth control during the trial and at least 1 year after completing the trial and must consent to a pregnancy test prior to every dose administration.
• Renal abnormality (please see section 7.5.1): defined as a serum-creatinine value above the upper limit of normal (age- and sex-matched) or a urine dipstick greater than 2 + protein.
• Hypocalcemia: any value (age-matched) below the normal range.
• History or evidence of an intestinal malabsorption syndrome.
• Patients with a significant drug-related adverse event in the original protocol.
• Patients who discontinued treatment in the original protocol ZOL446H2202.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Osteogenesis Imperfecta

Intervention(s)

Product Name: zoledronic acid
Product Code: ZOL446
Pharmaceutical Form: Solution for infusion

Primary Outcome(s)

Primary end point(s): • Bone-mineral density (BMD) measurements (lumbar spine and total body) by dual energy absorptiometry (DEXA)
• X-rays of the vertebral spine and the left hand: to determine vertebral spine length, bone cortical thickness and number of clinical fractures.
• Specialized serum tests to evaluate bone resorption and formation will be performed for C-telopeptide (CTX), N-terminal propeptide of type I collagen (P1NP), parathyroid hormone (PTH) and bone specific alkaline phosphatase (SAP).
• Bone Pain Assessment using the pediatric Wong-Baker FACES Pain Rating Scale.
• Grip Strength using dynamometry
• Clinical fractures
• Height using stadiometer
• Incidence of patients who need treatment before scheduled dosing visit.

Main Objective: to examine the long-term safety of two different dosage regiments of zoledronic acid over an additional 12 months in pediatric patients who have completed one-year of treatment of zoledronic acid in the core CZOL446H2202 study, with focus on general safety and renal safety.

Secondary Objective: to assess continued efficacy, compared to baseline (visit 1 of core) :
• % change in lumbar spine bone mineral density at mo 18 & 24
• change in Z score of lumbar spine at mo18 & 24
• # clinical fractures per patient over 12-mo ext & 24-mo total
• change in bone resorption / formation markers at mo15, 18, 21 & 24
• change in supine length/height at mo 15, 18, 21 & 24
• change in bone pain
• change in bone mineral content of total body at mo 18 & 24
• change in cortical bone thickness at mo 24
• change in vertebral spine length at mo 24
• change in grip strength at mo 15, 18, 21 & 24
• % of patients need treatment before scheduled dosing visits during the extension

Secondary ID(s)

CZOL446H2202E1