- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01417091
Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
A Randomized, Open Label Intra-patient Dose Escalation Study With an Untreated Reference Group to Evaluate Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Infusions of BPS804 in Adults With Moderate Osteogenesis Imperfecta
This is a randomized, open label intra-patient dose escalation study to evaluate safety and tolerability, pharmacokinetics, and pharmacodynamics of BPS804 in adults with osteogenesis imperfecta (OI).
Pharmacodynamic effect will be determined by serological biomarkers and radiologic assessments. In addition, tolerability and pharmacokinetics (PK) will be evaluated.
Studieoversigt
Detaljeret beskrivelse
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Bruxelles, Belgien, 1200
- Novartis Investigative Site
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Gent, Belgien, 9000
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canada, H3GIA6
- Novartis Investigative Site
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California
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Anaheim, California, Forenede Stater, 92801
- Novartis Investigative Site
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Florida
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Miramar, Florida, Forenede Stater, 33025
- Novartis Investigative Site
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Wuerzburg, Tyskland, 97074
- Novartis Investigative Site
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Osteogenesis imperfecta
- Two or more previous fractures
- Bone mineral density Z-score of ≤ -1.0 and > -4.0
Exclusion Criteria:
- Open epiphyses
- Fracture within last 2 weeks
- Treatment with bisphosphonates/teriparatide (last 6 months)
- Surgery within last year
Other protocol-defined inclusion/exclusion criteria may apply
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Behandlingsgruppe
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Ingen indgriben: Untreated reference group
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events)
Tidsramme: Day 1 through 141
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The assessment of safety will be based on primarily on the frequency of adverse events, laboratory abnormalities, and serious adverse events suspected by the investigators to be related to study treatments.
The AE collection period extends from the time of first study drug administration drug until study completion.
The intensity of each AE will be characterized and classified into 1 of the 3 generic categories (mild, moderate, or severe).
The number and percentage of patients with adverse events will be tabulated by treatment group, body system and preferred term.
The periods for adverse event tabulation will be from dose administration up to next dose administration if a further dose is given, and from dose administration to EOS for the last dose administration of a patient.
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Day 1 through 141
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Determination of pharmacodynamic effect by means of biomarkers
Tidsramme: Day 1 and Day 43
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Biomarker data from serum bone formation biomarkers: procollagen type I N-terminal propeptide, procollagen type I C-terminal propeptide, osteocalcin, and bone-specific alkaline phosphatase, and from serum bone resporption mbiomarkers: C-telopeptides of type I collagen cross-links, and N-telopeptides of type I collagen cross-links will be reported as concentration results, measured using a specific assay with a working range defined by the Lower limit of quantification and Upper limit of quantification.
It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05)
increase versus baseline in the BPS804 group on day 43.
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Day 1 and Day 43
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Change in Z-score from baseline to Day 141
Tidsramme: Day 1 and Day 141
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Bone mineral density will be assessed by dual-energy X-ray absorptiometry of the lumbar spine.
Analysis will include four vertebral levels from L1 to L4.
Individual vertebral levels may be excluded due to artifact.
Bone mineral density Z-scores will be used as these are a comparison of a patient's BMD to that of a patient of the same age, sex, and ethnicity.
The comparison of change from baseline with the matching change in the reference group will be done by 2-sample t-tests (1-sided).
It will be considered a sign for efficacy, if any of the above show significant (2-sided, alpha=0.05)
increase versus baseline in the BPS804 group on day 141.
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Day 1 and Day 141
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Determination of the serum concentration-time profiles of BPS804
Tidsramme: Day 1 (prior to administration and 3x after administration) and Days 2, 8, 15 (2x), 16, 29 (4x), 30, 36, 43, 57, 85, 113,141
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Individual and overlaying individual serum concentration-time profiles of BPS804 will be constructed from the serial sampling on Day 1 (prior to administration and 3x after administration) and Days 2, 8, 15 (2x), 16, 29 (4x), 30, 36, 43, 57, 85, 113,141.
In addition arithmetic and geometric mean serum concentration-time profiles of BPS804 will be constructed from the above data points.
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Day 1 (prior to administration and 3x after administration) and Days 2, 8, 15 (2x), 16, 29 (4x), 30, 36, 43, 57, 85, 113,141
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Determination of the area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the first dose
Tidsramme: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
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The area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the first dose will be derived using using non-compartmental methods from data collected on Day 1 (4x) and Days 2, and 8.
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Day 1 (prior to administration and 3x after administration) and Days 2, and 8
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Determination of the maximal concentration after the first dose
Tidsramme: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
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The maximal concentration after the first dose will be derived using using non-compartmental methods from data collected Day 1 (4x) and Days 2, and 8.
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Day 1 (prior to administration and 3x after administration) and Days 2, and 8
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Determination of the time of maximal concentration after the first dose
Tidsramme: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
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The time of maximal concentration after the first dose will be derived using using non-compartmental methods from data collected Day 1 (4x) and Days 2, and 8.
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Day 1 (prior to administration and 3x after administration) and Days 2, and 8
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Determination of the maximal concentration after the second dose
Tidsramme: Day 15 (prior to administration and 1x after administration) and Day 16
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The maximal concentration after the second dose will be derived using using non-compartmental methods from data collected from days 15 (2x) and 16.
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Day 15 (prior to administration and 1x after administration) and Day 16
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Determination of the time of maximal concentration after the second dose
Tidsramme: Day 15 (prior to administration and 1x after administration) and Day 16
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The time of maximal concentration after the second dose will be derived using using non-compartmental methods from data collected from days 15 (2x) and 16.
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Day 15 (prior to administration and 1x after administration) and Day 16
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Determination of the area under the serum concentration-time curve from time zero to infinity after the third dose
Tidsramme: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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The area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose will be derived using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
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Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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Determination of the area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration after the third dose
Tidsramme: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration after the third dose will be derived using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
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Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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Determination of the area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose
Tidsramme: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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The area under the serum concentration-time curve from time zero to the end of the dosing interval tau after the third dose will be derived using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
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Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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Determination of the maximal serum concentration after the third dose
Tidsramme: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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The maximal serum concentration after the third dose will be derived using using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
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Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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Determination of the time of maximal concentration after the third dose
Tidsramme: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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The time of maximal concentration after the third dose will be derived using using non-compartmental methods from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141.
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Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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Determination of the terminal elimination half-life after the third dose
Tidsramme: Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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The terminal elimination half-life after the third dose will be derived from data collected on Days 29 (4x), 30, 36, 43, 57, 85, 113, and 141 using a compound-specific modeling approach.
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Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
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Determination of the concentration of total sclerostin in serum
Tidsramme: Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141
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The function of sclerostin is described as an endogenous negative regulator of bone formation.
Total serum sclerostin will be measured from samples collected at screening and on days 1, 8, 15, 29, 36, 43, 57, 85, 113, and 141
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Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141
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Immunogenicity evaluation in serum
Tidsramme: Days 1, 29, 85, and 141
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Immunogenicity will only be assessed in patients randomized to the treatment group.
Anti-BPS804 antibodies will be measured in human serum on Days 1, 29, 85, and 141 An immunogenicity positive patient at end of study will be followed up until anti-BPS804 antibody levels are back to levels measured on Day 1.
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Days 1, 29, 85, and 141
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Samarbejdspartnere og efterforskere
Sponsor
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- CBPS804A2201
- 2011-001465-41 (EudraCT nummer)
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
produkt fremstillet i og eksporteret fra U.S.A.
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Kliniske forsøg med Osteogenesis Imperfecta
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Ultragenyx Pharmaceutical IncMereo BioPharmaAfsluttetOsteogenesis Imperfecta Type III | Osteogenesis Imperfecta Type IV | Osteogenesis Imperfecta, Type IForenede Stater, Canada, Danmark, Frankrig, Det Forenede Kongerige
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Nationwide Children's HospitalAfsluttetOsteogenesis Imperfecta Type III | Osteogenesis Imperfecta Type IIForenede Stater
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Emory UniversityIkke rekrutterer endnuOsteogenesis Imperfecta | Osteogenesis Imperfecta Type III
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Novartis PharmaceuticalsAfsluttetOsteogenesis ImperfectaForenede Stater
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Shriners Hospitals for ChildrenNovartisAfsluttet
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AmgenAfsluttetOsteogenesis Imperfecta (OI)Canada, Tjekkiet, Spanien, Det Forenede Kongerige, Forenede Stater, Italien, Ungarn, Australien, Belgien, Frankrig, Tyskland, Polen
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Angitia Incorporated LimitedRekrutteringOsteogenesis ImperfectaForenede Stater
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AmgenRekrutteringOsteogenesis ImperfectaForenede Stater, Det Forenede Kongerige, Kalkun, Ungarn, Tyskland, Schweiz, Spanien, Japan, Frankrig, Canada, Belgien, Polen, Australien, Østrig, Slovakiet
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Orthofix s.r.l.Ikke rekrutterer endnuOsteogenesis ImperfectaFrankrig
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Assiut UniversityRekruttering
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Ultragenyx Pharmaceutical IncNovartis; Mereo BioPharmaAfsluttet
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Ultragenyx Pharmaceutical IncMereo BioPharmaTrukket tilbageOsteogenesis ImperfectaForenede Stater
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Ultragenyx Pharmaceutical IncMereo BioPharmaAfsluttetOsteogenesis ImperfectaForenede Stater
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Ultragenyx Pharmaceutical IncNovartis; Mereo BioPharmaAfsluttetOsteoporose | OsteopeniForenede Stater
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Ultragenyx Pharmaceutical IncAktiv, ikke rekrutterendeOsteogenesis ImperfectaForenede Stater, Italien, Brasilien, Frankrig, Canada, Tyskland, Holland, Polen
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Ultragenyx Pharmaceutical IncMereo BioPharmaAktiv, ikke rekrutterendeOsteogenesis ImperfectaForenede Stater, Kalkun, Tyskland, Det Forenede Kongerige, Italien, Portugal, Canada, Australien, Argentina, Frankrig, Holland, Polen
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Ultragenyx Pharmaceutical IncMereo BioPharmaAfsluttetOsteogenesis Imperfecta Type III | Osteogenesis Imperfecta Type IV | Osteogenesis Imperfecta, Type IForenede Stater, Canada, Danmark, Frankrig, Det Forenede Kongerige
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ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)AfsluttetMavekræftForenede Stater