Clinical trial NCT01197300: 1 Year Open-label Extension to CZOL446H2337 Safety and Efficacy Trial of Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids
Official title: A 1-year, Multicenter, Open-label Extension to CZOL446H2337 to Evaluate Safety and Efficacy of Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis
Keywords: Osteoporosis, children and adolescents, zoledronic acid, chronic inflammation, Duchenne muscular dystrophy, glucocorticoids, chronic inflammatory conditions
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-09-09
Enrollment: 25
Sex: ALL
Minimum age (years): 5
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This 1-year open-label extension to CZOL446H2337 is designed to evaluate the safety and efficacy of zoledronic acid twice yearly in osteoporotic children treated with glucocorticoids.


Eligibility criteria: Key Inclusion criteria:

Written informed consent before any study-related procedure.

Group 1:

1. Children and adolescents, male or female, 6-19 years old, who met the inclusion criteria for entry into the Core study and who took at least one dose of study drug and have completed Visit 8 of the CZOL446H2337 Core study.
2. Patient must be enrolled into the extension at Visit 9 up to 10 months after Visit 5 (month 6) of the Core study.
3. Patients who followed the regimen of calcium and vitamin D intake as required in the Core study through diet or supplementation.

Group 2:

1. Children and adolescents, male or female, 5 - 17 years old who met the inclusion criteria for entry into the Core study but were not enrolled because of clinically significant back pain from vertebral fracture and the preexisting clinical care at the Investigator site is to treat this type of patient with a bisphosphonate.
2. Confirmed diagnosis of non-malignant conditions (including but not limited to rheumatic conditions, inflammatory bowel disease, Duchenne muscular dystrophy, nephrotic syndrome), treated with systemic glucocorticoids (i.v. or oral) within the 12 months preceding enrollment in the study (any duration)
3. LS-BMD Z-score of -0.5 or worse confirmed by the central imaging vendor
4. Evidence of at least 1 vertebral compression fracture (at least Genant Grade 1 vertebral compression or radiographic signs of vertebral compression) confirmed by central reading OR At least one lower OR 2 upper extremity long-bone, low-trauma, fracture which occurred sometime within the 2 years or preceding enrollment in the study, confirmed by radiological report. (\*Low trauma fracture is defined as falling from standing height or less).

Key Exclusion criteria:

1. Major protocol violation in the Core Study (Group 1 only).
2. Prior use of bisphosphonates (Group 2 only) or sodium fluoride (doses for osteoporosis not for dental hygiene).
3. Hypocalcemia and hypophosphatemia: any value (age-matched) below the normal range at Visit 8 or 8A.
4. Vitamin D deficiency (serum 25-hydroxy vitamin D concentrations of \< 20 ng/mL or \< 50 nmol/L) at Visit 8 (Group 1) or Visit 8A (Group 2).
5. Renal impairment defined as an estimated glomerular filtration rate (GFR) \< 60 mL/min/1.73 m2 at screening based on the Schwartz formula at Visit 8 or 8 A; a serum creatinine above the normal range at Visit 9 (Group 1) or an increase between Visit 8A and Visit 9 greater than 0.5 mg/dL (44.2 μmol/L) for Group 2.
6. Female patients of child bearing potential are eligible only if they are not pregnant/non-lactating. Females of child bearing potential must be practicing a medically acceptable form of birth control for greater than 2 months prior to screening visit and consent to pregnancy tests during the study.

Primary outcomes:
measure: Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids.
timeFrame: Baseline 1 (Visit 1 of the Core Study) through Month 24 (Visit 15/Final Extension Visit)
Secondary outcomes:
measure: Mean Change From Baseline 1 (Visit 1 of the Core Study) in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 18 and 24 by Core Treatment Group.
timeFrame: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
measure: Mean Change From Baseline 1 (Visit 1 of the Core Study) in Lumbar Spine Bone Mineral Content (BMC) at Month 18 and 24 by Core Treatment Group.
timeFrame: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
measure: Mean Change From Baseline 1 (Visit 1 of the Core Study) in Total Body BMC at Month 18 and 24 by Core Treatment Group.
timeFrame: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
measure: Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum P1NP at Month 18 and 24 by Core Treatment Group.
timeFrame: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
measure: Mean Change From Baseline 1 (Visit 1 of the Core Study) in BSAP at Month 18 and 24 by Core Treatment Group.
timeFrame: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
measure: Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum NTX at Month 18 and 24 by Core Treatment Group.
timeFrame: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
measure: Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum TRAP-5b at Month 18 and 24 by Core Treatment Group.
timeFrame: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
measure: Number of Participants With New Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group.
timeFrame: Month 24 (Visit 15/Final Extension Visit)
measure: Number of Participants With New Morphometric Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group.
timeFrame: Month 24 (Visit 15/Final Extension Visit)
measure: Percentage of Patients With Reduction in Pain From Baseline 1 (Visit 1 of the Core Study) at Month 15, 18, 21 and 24 by Core Treatment Group.
timeFrame: Month 15, Month 18, Month 21, Month 24
measure: Mean Change From Baseline (Core and Extension) in 2nd Metacarpal Cortical Width at Month 24 by Core Treatment Group.
timeFrame: Baseline 1 (Visit 1 of the Core Study) and Baseline 2 (Visit 9 of the Extension Study) through Month 24 (Visit 15/Final Extension Visit)
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Soweto
country: South Africa
facility: Novartis Investigative Site
state: Gauteng
city: West Midlands
country: United Kingdom
facility: Novartis Investigative Site
state: Birmingham
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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citation: Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998 Oct 1;339(14):947-52. doi: 10.1056/NEJM199810013391402.
citation: Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest. 1999 Nov;104(10):1363-74. doi: 10.1172/JCI6800.
citation: Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002 Feb 28;346(9):653-61. doi: 10.1056/NEJMoa011807.
citation: Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, Rauch F, Tugwell P, Moher D. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev. 2007 Oct 17;2007(4):CD005324. doi: 10.1002/14651858.CD005324.pub2.