Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
6. mai 2021 oppdatert av: 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.
Studieoversikt
Detaljert beskrivelse
This study was previously posted by Mereo BioPharma and was transferred to Ultragenyx in February 2021.
Studietype
Intervensjonell
Registrering (Faktiske)
10
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
-
Bruxelles, Belgia, 1200
- Novartis Investigative Site
-
Gent, Belgia, 9000
- Novartis Investigative Site
-
-
-
-
Quebec
-
Montreal, Quebec, Canada, H3GIA6
- Novartis Investigative Site
-
-
-
-
California
-
Anaheim, California, Forente stater, 92801
- Novartis Investigative Site
-
-
Florida
-
Miramar, Florida, Forente stater, 33025
- Novartis Investigative Site
-
-
-
-
-
Wuerzburg, Tyskland, 97074
- Novartis Investigative Site
-
-
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
18 år til 75 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
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
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: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Behandlingsgruppe
|
|
|
Ingen inngripen: Untreated reference group
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events)
Tidsramme: Day 1 through 141
|
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.
|
Day 1 through 141
|
|
Determination of pharmacodynamic effect by means of biomarkers
Tidsramme: Day 1 and Day 43
|
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.
|
Day 1 and Day 43
|
|
Change in Z-score from baseline to Day 141
Tidsramme: Day 1 and Day 141
|
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.
|
Day 1 and Day 141
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
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
|
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.
|
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
|
|
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
|
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.
|
Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
|
Determination of the maximal concentration after the first dose
Tidsramme: Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
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.
|
Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
|
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
|
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.
|
Day 1 (prior to administration and 3x after administration) and Days 2, and 8
|
|
Determination of the maximal concentration after the second dose
Tidsramme: Day 15 (prior to administration and 1x after administration) and Day 16
|
The maximal concentration after the second dose will be derived using using non-compartmental methods from data collected from days 15 (2x) and 16.
|
Day 15 (prior to administration and 1x after administration) and Day 16
|
|
Determination of the time of maximal concentration after the second dose
Tidsramme: Day 15 (prior to administration and 1x after administration) and Day 16
|
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.
|
Day 15 (prior to administration and 1x after administration) and Day 16
|
|
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
|
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.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
|
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
|
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.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
|
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
|
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.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
|
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
|
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.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
|
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
|
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.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
|
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
|
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.
|
Days 29 (prior to administration and 3x after administration) and 30, 36, 43, 57, 85, 113, and 141
|
|
Determination of the concentration of total sclerostin in serum
Tidsramme: Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141
|
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
|
Screening, Days 1, 8, 15, 29, 36, 43, 57, 85, 113, 141
|
|
Immunogenicity evaluation in serum
Tidsramme: Days 1, 29, 85, and 141
|
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.
|
Days 1, 29, 85, and 141
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
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
1. juni 2011
Primær fullføring (Faktiske)
1. desember 2012
Studiet fullført (Faktiske)
1. desember 2012
Datoer for studieregistrering
Først innsendt
4. august 2011
Først innsendt som oppfylte QC-kriteriene
12. august 2011
Først lagt ut (Anslag)
16. august 2011
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
11. mai 2021
Siste oppdatering sendt inn som oppfylte QC-kriteriene
6. mai 2021
Sist bekreftet
1. mai 2021
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- CBPS804A2201
- 2011-001465-41 (EudraCT-nummer)
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
produkt produsert i og eksportert fra USA
Nei
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. .