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1 Year Open-label Extension to CZOL446H2337 Safety and Efficacy Trial of Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01197300
First received: September 7, 2010
Last updated: June 10, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Osteoporosis
Drug: zoledronic acid
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Safety of zoledronic acid for the treatment of osteoporotic children treated with glucocorticoids. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To demonstrate that zoledronic acid given long-term, over an additional 12 months from the Core study (CZOL446H2337), is safe for the treatment of osteoporotic children treated with glucocorticoids (Group 1 only)


Secondary Outcome Measures:
  • Change from baseline (Visit 1 of the Core study) in LS BMD Z-score at Month 18 and 24 by core treatment group [ Time Frame: Month 18 & 24 ] [ Designated as safety issue: No ]
  • Change from baseline 1 (Visit 1 of the Core study) in LS and total body BMC at Month 18 and 24 by core treatment group. [ Time Frame: Month 18 & 24 ] [ Designated as safety issue: No ]
  • Change from baseline 1 in serum N-terminal propeptide type I collagen (P1NP), cross linked N-telopeptide (NTX), bone specific alkaline phosphatase (BSAP) and tartrate-resistant acid phosphatase isoform 5b (TRAP-5b) by core treatment group. [ Time Frame: Month 18 & 24 ] [ Designated as safety issue: No ]
  • Proportion of patients with new clinical vertebral fractures during the 12 month extension period by core treatment group. [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  • Proportion of patients with new morphometric vertebral fracture during the 12 month extension period by core treatment group. [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  • Change from baseline 1 (Visit 1 of the Core study) in pain using the Faces Pain Scale-Revised (FPS-R) at Month 15, 18, 21 and 24 by core treatment group. [ Time Frame: Month 15, 18, 21 and 24 ] [ Designated as safety issue: Yes ]
  • Change from baseline 1 (Visit 1 of the Core study) in 2nd metacarpal cortical width at month 24 by core treatment group. [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
  • Change from baseline 1(Visit 1 of the Core study) in bone age and 2nd metacarpal cortical width at month 24 by core treatment group. [ Time Frame: Month 24 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change from (Extension) baseline 2 (Visit 8A) in LS-BMD Z-score at Month 6 and 12. [ Time Frame: Month 6 and 12 ] [ Designated as safety issue: No ]
  • Change from (Extension) baseline 2 (Visit 8A) in LS and total body BMC at Month 6 and 12. [ Time Frame: Month 6 and 12 ] [ Designated as safety issue: No ]
  • Relative change from (Extension) Baseline 2 in serum N-terminal propeptide type I collagen (P1NP), cross linked N-telopeptide (NTX), bone specific alkaline phosphatase (BSAP) and tartrate-resistant acid phosphatase isoform 5b (TRAP-5b) at Month 6 and 12. [ Time Frame: Month 6 and 12 ] [ Designated as safety issue: No ]
  • Proportion of patients with new clinical vertebral fractures during the 12 month period. [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  • Proportion of patients with new morphometric vertebral fracture during the 12 month period. [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  • Change from (Extension) baseline 2 in pain using the Faces Pain Scale-Revised (FPS-R) at Month 3, 6, 9 and 12. [ Time Frame: Month 3, 6, 9 and 12 ] [ Designated as safety issue: Yes ]
  • Change from (Extension) baseline 2 in bone age and 2nd metacarpal cortical width at Month 12. [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • To demonstrate that zoledronic acid is safe for the treatment of osteoporotic children (with symptomatic vertebral fracture) treated with glucocorticoids, through the monitoring of relevant clinical and laboratory safety parameters. [ Time Frame: Until 30 days after the patient has stopped study participation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: October 2010
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: zoledronic acid
zoledronic acid
Drug: zoledronic acid

  Eligibility

Ages Eligible for Study:   5 Years to 19 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01197300

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Australia, New South Wales
Novartis Investigative Site Recruiting
Westmead, New South Wales, Australia, 2145
Canada, British Columbia
Novartis Investigative Site Completed
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
Novartis Investigative Site Recruiting
Ottawa, Ontario, Canada, K1H 8L1
Canada, Quebec
Novartis Investigative Site Recruiting
Montreal, Quebec, Canada, H3T 1C5
South Africa
Novartis Investigative Site Recruiting
Soweto, Gauteng, South Africa, 2013
Turkey
Novartis Investigative Site Recruiting
Izmir, Turkey, 35040
Novartis Investigative Site Recruiting
Pendik / Istanbul, Turkey, 1330
United Kingdom
Novartis Investigative Site Recruiting
West Midlands, Birmingham, United Kingdom, B4 6NH
Novartis Investigative Site Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Novartis Investigative Site Recruiting
Manchester, United Kingdom, M14 0JH
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications:
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01197300     History of Changes
Other Study ID Numbers: CZOL446H2337E1  2010-020399-41 
Study First Received: September 7, 2010
Last Updated: June 10, 2016
Health Authority: European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Canadian Institutes of Health Research
Belgium: Ministry of Social Affairs, Public Health and the Environment
United Kingdom: Department of Health
Poland: Ministry of Health
Romania: Ministry of Public Health
Turkey: Ministry of Health
South Africa: Department of Health
Russia: Ministry of Health of the Russian Federation
Hungary: Research Ethics Medical Committee

Keywords provided by Novartis:
Osteoporosis, children and adolescents, zoledronic acid, chronic inflammation, Duchenne muscular dystrophy, glucocorticoids

Additional relevant MeSH terms:
Glucocorticoids
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on December 07, 2016