An Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids
1. september 2020 oppdatert av: Novartis Pharmaceuticals
A Multicenter, Randomized, Double-blind, Placebo Controlled Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly Compared to Placebo in Osteoporotic Children Treated With Glucocorticoids.
This study was designed to evaluate the efficacy and safety of zoledronic acid compared to placebo in osteoporotic children treated with glucocorticoids
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
In March 2017, Novartis stopped enrollment as the study was not feasible to be conducted due to low enrollment and other recruitment challenges.
Patients receiving the treatment continued to receive the treatment per protocol.
Studietype
Intervensjonell
Registrering (Faktiske)
34
Fase
- Fase 3
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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New South Wales
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Westmead, New South Wales, Australia, 2145
- Novartis Investigative Site
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British Columbia
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Vancouver, British Columbia, Canada, V6H 3V4
- Novartis Investigative Site
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Manitoba
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Winnipeg, Manitoba, Canada, R3E 0Z2
- Novartis Investigative Site
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Ontario
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Ottawa, Ontario, Canada, K1H 8L1
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canada, H3T 1C5
- Novartis Investigative Site
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Montreal, Quebec, Canada, H3H 1P3
- Novartis Investigative Site
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Moscow, Den russiske føderasjonen, 119991
- Novartis Investigative Site
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Saint Petersburg, Den russiske føderasjonen, 195067
- Novartis Investigative Site
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Manchester, Storbritannia, M14 0JH
- Novartis Investigative Site
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Birmingham
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West Midlands, Birmingham, Storbritannia, B4 6NH
- Novartis Investigative Site
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Gauteng
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Soweto, Gauteng, Sør-Afrika, 2013
- Novartis Investigative Site
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Budapest, Ungarn, 1085
- Novartis Investigative Site
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
5 år til 17 år (Barn)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Key Inclusion Criteria:
- A diagnosis of chronic rheumatologic conditions or inflammatory bowel disease or Duchenne muscular dystrophy requiring systemic glucocorticoids (i.v. or oral) within 12 months prior to screening
- Lumbar Spine BMDZ-score of -0.5 or worse
- Evidence of at least at least 1 vertebral compression fracture of Genant Grade 1 or higher (or radiographic signs of vertebral fracture) within 1 month from Screening visit OR One or more, low-trauma, lower extremity long-bone fracture which occurred sometime within the 2 years PRECEDING enrollment in the study OR Two or more, low-trauma, upper extremity long-bone fractures which occurred sometime within the 2 years PRECEDING enrollment in the study
- Consent/assent to study participation
Key Exclusion Criteria:
- History of primary bone disease (OI, Idiopathic Juvenile Osteoporosis, Rickets/Osteomalacia)
- Any medical condition that might have interfered with the evaluation of lumbar spine BMD, such as severe scoliosis or spinal fusion. Patients with less than 3 evaluable vertebrae by Dual Energy X-ray Absorptiometry (DXA) evaluation in the region of interest lumbar 1 (L1) to lumbar 4 (L4),
- Hypocalcemia and hypophosphatemia
- Serum 25-hydroxy vitamin D concentrations of <20 ng/mL or <50 nmol/L
- estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m2
- serum creatinine increase between Visit 1 and Visit 2 >0.5 mg/dL (44.2 μmol/L)
- Uncontrolled symptoms of cardiac failure or arrhythmia
- Any prior use of bisphosphonates, or high dose sodium fluoride
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: Zoledronsyre
To ganger årlig 0,05 mg/kg (maks 5 mg) i.v infusjon (minst 30 minutter) av zoledronsyre
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intravenøs infusjon
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Placebo komparator: Placebo
Twice yearly i.v of infusion of Placebo (similar dosing as active drug)
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intravenøs infusjon
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 12
Tidsramme: Month 12
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Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 12.
The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor.
Positive changes from baseline indicated an improvement in condition.
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Month 12
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 6
Tidsramme: Month 6
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Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 6.
The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor.
Positive changes from baseline indicated an improvement in condition.
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Month 6
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Mean Change From Baseline in Lumbar Spine BMC at Month 6 and 12
Tidsramme: Month 6, Month 12
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Lumbar Spine BMC was determined by the central imaging vendor before first treatment and at Months 6 and 12.
The methods to be used to measure BMC were described in the respective DXA Manuals.
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Month 6, Month 12
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Mean Change From Baseline in Total Body BMC at Month 6 and 12
Tidsramme: Month 6, Month 12
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Total body BMC was all determined by the central imaging vendor before first treatment and at Months 6 and 12.
The methods to be used to measure BMC were described in the respective DXA Manuals.
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Month 6, Month 12
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Mean Change From Baseline in Serum P1NP at Months 6 and 12
Tidsramme: Month 6, Month 12
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Serum Procollagen type 1 amino-terminal propeptide (P1NP) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual.
The samples were analyzed in batches at the laboratory.
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Month 6, Month 12
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Mean Change From Baseline in BSAP at Months 6 and 12
Tidsramme: Month 6, Month 12
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Bone specific alkaline phosphatase (BSAP) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual.
The samples were analyzed in batches at the laboratory.
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Month 6, Month 12
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Mean Change From Baseline in Serum NTX at Months 6 and 12
Tidsramme: Month 6, Month 12
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Serum Cross linked N-telopeptide (NTX) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual.
The samples were analyzed in batches at the laboratory.
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Month 6, Month 12
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Mean Change From Baseline in Serum TRAP-5b at Months 6 and 12
Tidsramme: Month 6, Month 12
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Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual.
The samples were analyzed in batches at the laboratory.
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Month 6, Month 12
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Number of Participants With New Vertebral Fractures at Month 12
Tidsramme: Month 12
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New vertebral fractures were defined as fractures of Genant Grade 1 or higher that occurred at lumbar or thoracic spine from first dose infusion to the end of the study.
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Month 12
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Mean Change From Baseline in Vertebral Morphometry at Month 12
Tidsramme: Month 12
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Vertebral morphometry (or concave index) was calculated using the average ratio between mid-height and posterior height from L1 to L4 and performed by a central reader.
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Month 12
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Percentage of Patients With Reduction in Pain at Months 3, 6, 9 and 12
Tidsramme: Month 3, Month 6, Month 9 and Month 12
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Pain was evaluated at each visit (in office and telephone visit) at randomization, Months 3, 6, 9 and 12 using the Faces Pain Scale-Revised (FPS-R).
Children were selecting the face that best fits their pain.
The pain score ranged from 0 (No Pain) to 10 (Very Much Pain).
The reduction in pain from baseline by visit was evaluated based on whether or not patients had a decrease in their FPS-R from baseline.
If pain remained the same or worsened from baseline a patient was classified as '0' and if the pain scale decreased then the patient was classified as '1'.
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Month 3, Month 6, Month 9 and Month 12
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Mean Change From Baseline in 2nd Metacarpal Cortical Width at Month 12
Tidsramme: Month 12
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Left posteroanterior (PA) hand/wrist X-ray were taken at Visit 1 and at the Month 12 visit to assess bone age and the between-treatment differences for change in 2nd metacarpal cortical width at Month 12 relative to baseline.
If a fracture of the left upper extremity precluded radiographic imaging, then the right hand was evaluated for this purpose.
In this case, the right hand was be imaged at both Visit 1 and at Month 12.
The information was used in the assessment of bone density.
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Month 12
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Urinary Concentration of Zoledronic Acid at Month 12
Tidsramme: Month 12
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Urine was collected overnight or for at least 4 waking hours from all patients able to provide specimens, to measure urinary concentration of zoledronic acid at Month 12.
Only descriptive analysis done.
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Month 12
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Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids
Tidsramme: Baseline through Month 12
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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 is safe for the treatment of osteoporotic children treated with glucocorticoids through the monitoring of relevant clinical and laboratory safety parameters.
Only descriptive analysis done.
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Baseline through Month 12
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Samarbeidspartnere og etterforskere
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Sponsor
Publikasjoner og nyttige lenker
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Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
4. desember 2008
Primær fullføring (Faktiske)
5. mars 2018
Studiet fullført (Faktiske)
5. mars 2018
Datoer for studieregistrering
Først innsendt
26. november 2008
Først innsendt som oppfylte QC-kriteriene
26. november 2008
Først lagt ut (Anslag)
27. november 2008
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
2. september 2020
Siste oppdatering sendt inn som oppfylte QC-kriteriene
1. september 2020
Sist bekreftet
1. september 2020
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- CZOL446H2337
- 2008-001252-52 (EudraCT-nummer)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
UBESLUTTE
IPD-planbeskrivelse
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .