Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
6 de maio de 2021 atualizado por: 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.
Visão geral do estudo
Descrição detalhada
This study was previously posted by Mereo BioPharma and was transferred to Ultragenyx in February 2021.
Tipo de estudo
Intervencional
Inscrição (Real)
10
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Wuerzburg, Alemanha, 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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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos a 75 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Grupo de tratamento
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Sem intervenção: Untreated reference group
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Safety and tolerability (composite outcome: standard laboratory, (serious) adverse events)
Prazo: 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
Prazo: 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
Prazo: 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 resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Determination of the serum concentration-time profiles of BPS804
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
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Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de junho de 2011
Conclusão Primária (Real)
1 de dezembro de 2012
Conclusão do estudo (Real)
1 de dezembro de 2012
Datas de inscrição no estudo
Enviado pela primeira vez
4 de agosto de 2011
Enviado pela primeira vez que atendeu aos critérios de CQ
12 de agosto de 2011
Primeira postagem (Estimativa)
16 de agosto de 2011
Atualizações de registro de estudo
Última Atualização Postada (Real)
11 de maio de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
6 de maio de 2021
Última verificação
1 de maio de 2021
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- CBPS804A2201
- 2011-001465-41 (Número EudraCT)
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Não
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
produto fabricado e exportado dos EUA
Não
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