| DEC-NET Serial number GB387 |
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| Published online | 11/04/2005 12.51.00 |
| Last updated | 10/04/2006 10.07.46 |
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| Other protocol ID number | CZOL446H2202 |
| This trial has been approved by an ethics committee |
| Current trial status | Open (actively recruiting new participants) |
Target N. of subjects
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132
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Major Disease
(ICD9 class) | OSTEOGENESIS IMPERFECTA |
| Experimental drug |
Zoledronic acid
Treatment regimen (dosage and duration)
0.05mg/kg |
| Control drug |
Pamidronate
Treatment regimen (dosage and duration)
1.0mg/kg/day or 3.0mg/kg |
| Gender | Both |
| Age (range) | 3-17 |
Eligibility criteria |
| Inclusion criteria |
| Any child with phenotypic OI type III or IV.
All patients must have completed two weeks of treatment with vitamin D 800 IU daily and elemental calcium 500mg (or equivalent described in Protocol) daily (pre-study and/or within the screening period) prior to the first administration of zoledronic acid or pamidronate
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| Exclusion criteria |
| Treatment with any investigational drug within the past 30 days
Female patients of child bearing potential are eligible only if they are: not pregnant/non lactating, are sexually abstinent or are surgically sterile
History of noncompliance to medical regimens and patients who are considered potentially unreliable
Any disease or planned therapy which will interfere with the procedures or data collection of this trial
Any surgical bone-lengthening procedure, e.g. Ilizerove procedure planned/scheduled to occur during trial
History of allergic reaction or hypersensitivity to bisphosphonates
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Trial design/methodology |
| Phase | 2 |
| Kind of study | Efficacy
Safety
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| Design | Controlled
Randomised
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| Purpose of study |
| To investigate whether zoledronic acid is comparable to pamidronate in children in respect to therapeutic efficacy and safety when assessing the percentage change in bone mineral density in children with severe osteogenesis imperfecta |
| Primary outcomes |
| Percentage change in bone mineral density after 12 months therapy. |
| Secondary outcomes |
| Change in bone mineral density z-score and the incidence of fractures, assessed radiologically in each group |
| Summary of study design, objectives, and ongoing research findings |
| This will be an international, multicentre, randomised, open-label, parallel group efficacy and safety trial that will evaluate the percentage change in lumbar spine bone mineral density at month 12 relative to baseline using 0.05 mg/kg of intravenous zoledronic acid compared to 3.0 mg/kg of intravenous pamidronate in children with severe osteogenesis imperfecta. The percentage change in lumbar spine bone mineral density will aslo be compared between the zoledronic acid treated and pamidronate treated patients at 6 months as an exploratory objective. The patients will be randomised to either zoledronic acid or pamidronate in a 1:1 ratio. The study is designed to show that zoledronic acid is no worse than pamidronate within the margin of 13%. The duration of the study is 13 months; the actual study period is 12 months which is preceded by a 4 week screening period. Patients will return for four doses of drug every three months. After every IV administration, they will also return for visits nine to eleven days after their IV dose to have serum electrolytes (including total serum calcium, phosphorus, magnesium and albumin) checked, as well as their serum creatinine and a urine dipstick assessment for protein. There will be a total of 10 visits over the 13 month period of time.
Since the pamidronate IV infusion must occur over three days, patients randomised to the pamidronate treatment arm will be hospitalised for 3 days at every IV dose administration.
Sites will call all patients at scheduled monthly visits for completion of the Wong-Baker FACES Pain rating scale thoughout the study, except for those months where there is a scheduled on-site visit.
Grip strength will be assessed (in patients who are willing and able to cooperate) with the dominant hand using a hand dynamometer every three months. If the dominant hand cannot be used at any visit because of a fracture, risk of fracture or pain, then the assessment will not be made and this will be documented appropriately.
DEXA measurements of the lumbar spine and total body and X-rays of the hand will be done at randomisation, Visit 6 (Day 182) and final visit. X-ray of the vertebral spine will be done at randomisation and final visit.
One hundred and thirty-two patients will be randomised (66 patients per treatment group). Enrollment will be competitive and will stop when the target number of patients is reached.
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