A one year extension study to CZOL446H2337, multi-center, to evaluate safety and efficacy of zoledronic acid given to all patients every six months in children with weakened bone treated with steroids

• Register: EUCTR
• Last refreshed on: 20 July 2020
• Main ID: EUCTR2010-020399-41-GB
• Date of registration: 24/01/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A one year extension study to CZOL446H2337, multi-center, to evaluate safety and efficacy of zoledronic acid given to all patients every six months in children with weakened bone treated with steroids
• Scientific 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
• Date of first enrolment: 25/03/2013
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020399-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Germany, Hungary, Italy, Poland, Russian Federation, South Africa, Turkey, United Kingdom

Contacts

• Name: TBI
• Affiliation: TBI

• Name: TBI
• Affiliation: TBI

Key inclusion & exclusion criteria

Inclusion criteria:
Signed consent/assent to study participation.
Group 1:
•Children and adolescents, male or female, between 6 to 19 years of age who met the inclusion criteria for entry into the Core study and who took at least one dose of study drug in and have completed Visit 8 of the CZOL446H2337 Core study.
• Patient must be enrolled into the extension at visit 9 up to 10 months after at Visit 5 of the Core study.
• Patients who followed the regimen of calcium and vitamin D intake as required in the Core study
Group 2 :
• Children and adolescents, male or female, between 5 to 17 years of age 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 Investigator’s site is to treat this type of patient with a bisphosphonate.
• 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)
• Lumbar Spine-BMD Z-score of - 0.5 or worse confirmed by the central imaging
• Evidence of at least 1 vertebral compression fracture (at least Genant Grade 1 vertebral compression or radiographic signs of vertebral compression*) seen on X-ray within 1 month of or at screening visit confirmed by central reading.
*Radiographic signs of vertebral compression fracture include loss of endplate parallelism, vertebral buckling and endplate interruption.
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Patients who demonstrated a 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)
• Vitamin D deficiency (serum 25-hydroxy vitamin D concentration of <20 ng/ml or <50 nmol/L) at Visit 8 (Group 1) or Visit 8A (Group 2)
• Hypocalcaemia and hypophosphatemia: any value (age-matched) below the normal range 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 based on the Schwartz formula at Visit 8 (Group 1) or Visit 8A (Group 2). 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.



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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Treatment of osteoporosis in a paediatric population (aged 5 to 19 years old) treated with systemic glucocorticoids (i.v. or oral)
MedDRA version: 20.0 Level: PT Classification code 10031282 Term: Osteoporosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Aclasta®
Product Name: Aclasta®
Product Code: ZOL446
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ZOLEDRONIC ACID
CAS Number: 118072-93-8
Current Sponsor code: ZOL446
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Main Objective: 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.

Primary end point(s): Safety assessments will consist of:
• monitoring and recording of all adverse events and serious adverse events,
• the performance of physical examinations including oral examinations for exposed bone.
• the regular laboratory monitoring of hematology, blood chemistry and urinalysis, regular measurement of vital signs, and
• renal function (serum creatinine & GFR).

Secondary Objective: To evaluate
Group 1
•change from baseline1(Core study) in LS areal BMD Z-score, LS and total body BMC at Month 18 & 24
• the change from baseline1 in serum P1NP, NTX, BSAP and TRAP-5b at Month 18 & 24
•change from baseline1 in pain using FPS-R at Month 15, 18, 21 & 24
•change from baseline1 in bone age & 2nd metacarpal cortical width at month 24
Group 2:
•change from baseline2 (Extension study) in LS areal BMD Z-score, LS and total body BMC at Month 6 & 12
•change from baseline2 in serum P1NP, NTX, BSAP and TRAP-5b) at Month 6 & 12
•change from baseline2 in pain using FPS-R at Month 3, 6, 9 & 12
•change from baseline2 in bone age and 2nd metacarpal cortical width at month 12
Both groups:
•proportion of patients with new clinical vertebral fractures and new morphometric vertebral fracture during 12 month period.
To demonstrate zoledronic acid is safe for treatment of osteoporotic children treated with glucocorticoids

Timepoint(s) of evaluation of this end point: • Monitoring and recording of all adverse events and serious adverse events:
At each visit during the study
• Physical examination including oral examination:
At visits 9, 12 and Visit 15
• Vital signs:
Blood pressure and pulse rate: Visits 8 (Group 1 only), 8A (Group 2 only), Visits 9, 12 and 15
• Sitting and standing height and weight measurements: Visits 8 (Group 1 only), 8A (Group 2 only), Visits 9, 12 and 15
• Laboratory evaluations:
Central laboratory test (hematology, biochemistry and urinalysis): Visits 8A (Group 2 only), Visits 9, 12 and 15.
Additional lab test for renal monitoring: Visits 9, 10, 12, 13 and 15.

Secondary Outcome(s)

Secondary end point(s): The efficacy variables will be measured using the following techniques:
• vertebral morphometric fractures
• clinical fractures
• DXA measurements
• bone marker analysis
• height measurements
• bone age and metacarpal cortical width assessment
• pain assessment

Timepoint(s) of evaluation of this end point: •Vertebral morphometric fractures:
At final visit of Core study (Group1) or Visit 8A (Group2) and Visit 15
•Clinical fractures:
At final visit of the Core study (Group 1) or Visit 8A (Group2) and at each Visits
•DXA measurements:
At final visit of Core study (Group 1) or Visit 8A (for Group 2), Visit 9 and 15.
•Bone marker Analysis:
At final visit of Core study (Group 1) or Visit 9 (Group 2), Visit 12 and 15
•Height measurements:
At final visit of Core study (Group 1) or Visit 8A/or 9 (Group 2), Visit 12 and 15
•Bone age and metacarpal carpal cortical width assessment:
At final visit of Core study (Group 1) or Visit 8A (Group 2) and Visit 15.
•Pain Assessment:
At final visit of Core study (Group 1) and Visit 9, 11, 12, 14 and 15.

Secondary ID(s)

CZOL446H2337E1

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 25/03/2013
Contact:

Results

• Results available: Yes
• Date Posted: 04/09/2019
• Date Completed: 27/02/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-020399-41/results