Study of Resmetirom in Children and Adolescents With MASH
A Phase 2a, Multicenter, Open-label, Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Resmetirom in Pediatric Subjects Ages 6-17 Years With MASH With Fibrosis Stage F1-F3
Visão geral do estudo
Status
Status
Condições
Condições
Intervenção / Tratamento
Intervenção / Tratamento
Tipo de estudo
Tipo de estudo
Inscrição (Estimado)
Inscrição
Estágio
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
Contato de estudo
- Nome: Tom Hare
- Número de telefone: 267-406-0611
- E-mail: info@madrigalpharma.com
Locais de estudo
-
-
Indiana
-
Indianapolis, Indiana, Estados Unidos, 46402
- Recrutamento
- Riley Hospital for Children at IU Health
-
-
Critérios de participação
Critérios de elegibilidade
Critérios de elegibilidade
Idades elegíveis para estudo
- Filho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Male or female participants 6 to 17 years of age, inclusive.
- Parent(s) or legal guardian(s) able to provide written informed consent (as required by local regulations), with participant assent obtained as applicable.
- Diagnose of MASH with fibrosis stage F1-F3 based on a liver biopsy obtained within 24 months before Screening.
- Hepatic fat fraction ≥8% by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) obtained during the Screening period.
- Able to swallow study tablets.
- Females of childbearing potential must have a negative pregnancy test at screening, must not be pregnant or breastfeeding, and must agree to use a highly effective method of contraception during the study and for at least 30 days after the last dose of study drug. Premenarchal participants and those not of childbearing potential are eligible without contraception.
Exclusion Criteria:
- Previous exposure to resmetirom.
- Clinically significant liver disease other than MASH or evidence of cirrhosis (F4), decompensated liver disease, or other hepatic conditions that may interfere with study participation or interpretation of results.
- Clinically significant thyroid disease or use of thyroid replacement therapy, triiodothyronine, thyroxine, or other prohibited thyroid medications.
- Use of prohibited concomitant medications, including medications known to affect hepatic steatosis or liver function, lipid-lowering therapies, CYP2C8 inhibitors, OATP1B1/OATP1B3/BCRP inhibitors, protease inhibitors, St. John's Wort, or other medications prohibited by the protocol.
- Use of glucagon-like peptide-1 (GLP-1) receptor agonists unless on a stable dose for at least 24 weeks before screening.
- Clinically significant alcohol or substance abuse, or regular use of tobacco/nicotine products within 6 months before screening.
- Active or clinically significant infection, including chronic hepatitis B or hepatitis C infection, HIV infection, or other immunocompromising conditions.
- History or presence of clinically significant cardiovascular, pulmonary, renal, gastrointestinal, neurologic, hematologic, endocrine, psychiatric, or other medical conditions that, in the opinion of the Investigator, could interfere with study participation or interpretation of study results.
- History of malignancy within the past 5 years (except adequately treated non-melanoma skin cancer or other protocol-permitted exceptions).
- History of organ transplantation or known immunocompromised status.
- Participation in another investigational study within 60 days or 5 half-lives (whichever is longer) before screening, unless permitted by the protocol.
- Major surgery within 6 weeks before screening.
- Known hypersensitivity to resmetirom or any excipient.
- Females who are pregnant or breastfeeding.
- Any condition that, in the opinion of the Investigator, would compromise participant safety, compliance, or the integrity of the study.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Número de braços
Armas e Intervenções
Grupo de Participantes / BraçoGrupo de Participantes / Braço |
Intervenção / TratamentoIntervenção / Tratamento |
|---|---|
|
Experimental: Adolescent Dose-Escalation Cohort 1
Adolescents participants 12 to 17 years of age receive the first planned dose level of oral resmetirom once daily for approximately 14 days
|
Resmetirom (MGL-3196) : Oral resmetirom administered once daily.
Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design.
Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
|
|
Experimental: Adolescent Dose-Escalation Cohort 2
Adolescent participants 12 to 17 years of age receive the second planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
|
Resmetirom (MGL-3196) : Oral resmetirom administered once daily.
Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design.
Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
|
|
Experimental: Adolescent Dose-Escalation Cohort 3
Adolescent participants 12 to 17 years of age receive the third planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
|
Resmetirom (MGL-3196) : Oral resmetirom administered once daily.
Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design.
Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
|
|
Experimental: Adolescent Dose-Escalation Cohort 4
Adolescent participants 12 to 17 years of age receive the fourth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
|
Resmetirom (MGL-3196) : Oral resmetirom administered once daily.
Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design.
Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
|
|
Experimental: Adolescent Dose-Escalation Cohort 5
Adolescent participants 12 to 17 years of age receive the fifth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
|
Resmetirom (MGL-3196) : Oral resmetirom administered once daily.
Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design.
Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
|
|
Experimental: Child Dose-Escalation Cohort 6
Children participants 6 to 11 years of age receive the first planned dose level of oral resmetirom once daily for approximately 14 days.
|
Resmetirom (MGL-3196) : Oral resmetirom administered once daily.
Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design.
Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
|
|
Experimental: Child Dose-Escalation Cohort 7
Children participants 6 to 11 years of age receive the second planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
|
Resmetirom (MGL-3196) : Oral resmetirom administered once daily.
Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design.
Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
|
|
Experimental: Child Dose-Escalation Cohort 8
Children participants 6 to 11 years of age receive the third planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
|
Resmetirom (MGL-3196) : Oral resmetirom administered once daily.
Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design.
Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
|
|
Experimental: Child Dose-Escalation Cohort 9
Children participants 6 to 11 years of age receive the fourth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
|
Resmetirom (MGL-3196) : Oral resmetirom administered once daily.
Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design.
Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
|
O que o estudo está medindo?
Medidas de resultados primários
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Safety and tolerability of multiple ascending doses of resmetirom
Prazo: Baseline through approximately Day 21 (or the protocol-defined safety follow-up period)
|
Safety and tolerability will be assessed by the incidence and severity of adverse events, serious adverse events, clinical laboratory evaluations, vital signs, 12-lead electrocardiograms, physical examinations, and other protocol-defined safety assessments.
|
Baseline through approximately Day 21 (or the protocol-defined safety follow-up period)
|
Medidas de resultados secundários
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Pharmacokinetic parameters of resmetirom (MGL-3196) and its metabolite (MGL-3623)
Prazo: Day 1 through Day 14
|
Pharmacokinetic parameters of resmetirom and MGL-3623 following single and repeated dosing, including CL/F (parent only), Vz/F (parent only), Cmax, AUC0-24, and AUC0-∞ after the first dose, and CL/F (parent only), Cmax, and AUC0-24 following repeated dosing, as applicable.
|
Day 1 through Day 14
|
|
Pharmacodynamic biomarkers associated with resmetirom exposure
Prazo: Baseline through Day 21
|
Changes in pharmacodynamic biomarkers, including thyroid axis markers, sex hormone-binding globulin, and lipid parameters and their relationship to dose and/or plasma concentrations of resmetirom.
|
Baseline through Day 21
|
Colaboradores e Investigadores
Patrocinador
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Início do estudo
Conclusão Primária (Estimado)
Conclusão Primária
Conclusão do estudo (Estimado)
Conclusão do estudo
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Primeira postagem
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última Atualização Postada
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
Outros números de identificação do estudo
- MGL-3196-29
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .