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

NCT01197300 | Completed Phase 3 Results DMC

• 2 other identifiers: CZOL446H2337E12010-020399-41
• Study Type: interventional
• Target: 25
• Locations: 6 countries
• Sites: 10

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.

Conditions

Osteoporosis

Keywords

Osteoporosis, children and adolescents, zoledronic acid, chronic inflammation, Duchenne muscular dystrophy, glucocorticoids, chronic inflammatory conditions

Outcome Measures

Primary Outcomes (1)

• Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids.

  Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) 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 through the monitoring of relevant clinical and laboratory safety parameters.

  Baseline 1 (Visit 1 of the Core Study) through Month 24 (Visit 15/Final Extension Visit)

Secondary Outcomes (11)

• 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.

  Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

• 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.

  Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

• Mean Change From Baseline 1 (Visit 1 of the Core Study) in Total Body BMC at Month 18 and 24 by Core Treatment Group.

  Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

• Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum P1NP at Month 18 and 24 by Core Treatment Group.

  Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

• Mean Change From Baseline 1 (Visit 1 of the Core Study) in BSAP at Month 18 and 24 by Core Treatment Group.

  Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

Study Arms (1)

Zoledronic acid

EXPERIMENTAL

Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid

Drug: Zoledronic acid

Interventions

Zoledronic acid DRUG

intravenous infusion

Zoledronic acid

Eligibility Criteria

• Age: 5 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written informed consent before any study-related procedure.
• Group 1:
• Patient must be enrolled into the extension at Visit 9 up to 10 months after Visit 5 (month 6) of the Core study.
• Patients who followed the regimen of calcium and vitamin D intake as required in the Core study through diet or supplementation.
• Group 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)
• LS-BMD Z-score of -0.5 or worse confirmed by the central imaging vendor
• 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).

You may not qualify if:

• Major protocol violation in the Core Study (Group 1 only).
• Prior use of bisphosphonates (Group 2 only) or sodium fluoride (doses for osteoporosis not for dental hygiene).
• Hypocalcemia and hypophosphatemia: any value (age-matched) below the normal range at Visit 8 or 8A.
• 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).
• 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.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Vancouver, British Columbia, V6H 3V4, Canada

Location

Novartis Investigative Site

Ottawa, Ontario, K1H 8L1, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3H 1P3, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1C5, Canada

Location

Novartis Investigative Site

Budapest, 1085, Hungary

Location

Novartis Investigative Site

Moscow, 119991, Russia

Location

Novartis Investigative Site

Saint Petersburg, 195067, Russia

Location

Novartis Investigative Site

Soweto, Gauteng, 2013, South Africa

Location

Novartis Investigative Site

West Midlands, Birmingham, B4 6NH, United Kingdom

Location

Related Publications (5)

• Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22. doi: 10.1056/NEJMoa067312.

  PMID: 17476007 BACKGROUND

• 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.

  PMID: 9753709 BACKGROUND

• 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.

  PMID: 10562298 BACKGROUND

• 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.

  PMID: 11870242 BACKGROUND

• 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.

  PMID: 17943849 BACKGROUND

MeSH Terms

Conditions

Osteoporosis; Muscular Dystrophy, Duchenne

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2010
• First Posted: September 9, 2010
• Study Start: October 25, 2010
• Primary Completion: February 27, 2019
• Study Completion: February 27, 2019
• Last Updated: September 20, 2019
• Results First Posted: September 20, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

HU (1); AU (1); ZA (1); RU (2); GB (1); CA (4)