- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico 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.
Descripción general del estudio
Descripción detallada
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Wuerzburg, Alemania, 97074
- Novartis Investigative Site
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Bruxelles, Bélgica, 1200
- Novartis Investigative Site
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Gent, Bélgica, 9000
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canadá, H3GIA6
- Novartis Investigative Site
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California
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Anaheim, California, Estados Unidos, 92801
- Novartis Investigative Site
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Florida
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Miramar, Florida, Estados Unidos, 33025
- Novartis Investigative Site
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Grupo de tratamiento
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Sin intervención: Untreated reference group
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Determination of the serum concentration-time profiles of BPS804
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- CBPS804A2201
- 2011-001465-41 (Número EudraCT)
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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