Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
6. května 2021 aktualizováno: Ultragenyx Pharmaceutical Inc
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.
Přehled studie
Detailní popis
This study was previously posted by Mereo BioPharma and was transferred to Ultragenyx in February 2021.
Typ studie
Intervenční
Zápis (Aktuální)
10
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Bruxelles, Belgie, 1200
- Novartis Investigative Site
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Gent, Belgie, 9000
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Kanada, H3GIA6
- Novartis Investigative Site
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Wuerzburg, Německo, 97074
- Novartis Investigative Site
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California
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Anaheim, California, Spojené státy, 92801
- Novartis Investigative Site
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Florida
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Miramar, Florida, Spojené státy, 33025
- Novartis Investigative Site
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let až 75 let (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Léčebná skupina
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Žádný zásah: Untreated reference group
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events)
Časové okno: 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
Časové okno: 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
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Determination of the serum concentration-time profiles of BPS804
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. června 2011
Primární dokončení (Aktuální)
1. prosince 2012
Dokončení studie (Aktuální)
1. prosince 2012
Termíny zápisu do studia
První předloženo
4. srpna 2011
První předloženo, které splnilo kritéria kontroly kvality
12. srpna 2011
První zveřejněno (Odhad)
16. srpna 2011
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
11. května 2021
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
6. května 2021
Naposledy ověřeno
1. května 2021
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- CBPS804A2201
- 2011-001465-41 (Číslo EudraCT)
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ne
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
produkt vyrobený a vyvážený z USA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .