Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment (HARMONY)
Um estudo de fase 3, tratamento de grupos paralelos, cego, randomizado e controlado por placebo para avaliar a eficácia e segurança da pegtibatinase administrada por via subcutânea, além do tratamento padrão em participantes com homocistinúria clássica devido à deficiência de cistationina beta sintase (HARMONIA)
Researchers are looking for a better way to treat people living with classical homocystinuria (HCU), a rare inherited condition. It is caused by changes in the cystathionine beta-synthase (or "CBS") gene and prevents an enzyme from working correctly in the body. This enzyme helps break down homocysteine, which is produced when the body processes methionine from protein-containing foods. This helps keep homocysteine and methionine at healthy levels. When this enzyme is not working, homocysteine and methionine build up in the blood and then spread into different tissues of the body and stop these body tissues from working normally.
People living with HCU can experience problems with their vision, bones, blood vessels, thinking, learning, and memory. Available treatments for HCU include a low-methionine diet (typically achieved by limiting protein-containing foods), a methionine-free protein supplement to help meet daily protein needs, and betaine (Cystadane®). These treatments are either not sufficient or are hard to take for many patients.
Pegtibatinase was designed by researchers to act like the CBS enzyme, which is missing or not working properly in people living with HCU. Researchers are studying whether adding pegtibatinase to standard treatment can lower homocysteine levels.
Researchers want to learn how safe and effective pegtibatinase is, how it moves through and affects the body, and how it may affect the daily lives of people with HCU.
The study plans to enroll participants from the US, Australia, Belgium, France, Germany, Ireland, Italy, Poland, Portugal, Qatar, Saudi Arabia, Spain, Turkey, and the United Kingdom. Many study visits may happen at home, depending on where you live and local regulations. Some visits may include a home nurse and telemedicine appointments with the study doctor.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Primary Objective:
Researchers want to learn more about how pegtibatinase will affect homocysteine and methionine levels when it is injected under the skin in participants already receiving standard treatment.
Blood tests will be used to measure changes in these levels during the study.
Secondary Objectives:
Researchers also want to learn:
- Is pegtibatinase safe and tolerable (how does it make participants feel)?
- How does pegtibatinase move throughout the body?
- Does pegtibatinase produce antibodies (proteins the body makes that may stop pegtibatinase from working or cause side effects)?
- How does pegtibatinase affect daily lives of participants with HCU? Researchers will use blood tests, urine tests, physical examinations, and questionnaires to answer these questions.
Study Population and Treatments:
This is a global study will include children and adults from 12 to 65 years old. Participants in the study will take their standard of care treatment. Participants will be put into 1 of 2 groups at random (like the flip of a coin) to take either:
- pegtibatinase, or
- an injection that does not have any medicine in it (or "placebo"). These are given as injections under the skin 2 times a week for up to 24 weeks. Neither the researchers nor the participant knows which treatment they are getting until the study is complete.
Study Duration and Visits:
Participants may be in the study for up to 38 weeks, including the screening period of up to 4 weeks, a pre-treatment period of up to 6 weeks where the participants will discuss their current diet with a dietitian (a health professional specialized in nutrition), a blinded treatment period of up to 24 weeks, and a safety follow-up visit completed 4 weeks after the last dose of study medication. Participants who complete the blinded treatment period may qualify to join the ENSEMBLE study before finishing the safety follow-up visit.
Participants who meet all study requirements may have up to 58 study visits. Visits may take place at a study center, at home, or by telemedicine.
These visits can include:
- Blood and urine tests
- Physical examinations
- Questionnaires
- Injections
- Questions about how they are feeling or any problems they are having
Safety / Adverse Events:
Researchers will monitor participants for any medical problems that occur during the study. Participants will have regular laboratory tests, health checkups, and study visits to monitor their health and safety.
Benefit-risk Conclusion:
Researchers have worked to reduce risks to participants in this study. They believe the risks of taking pegtibatinase in this study are justified by the potential benefits that they think pegtibatinase may have for people with HCU.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 3
Contactos e Locais
Contato de estudo
- Nome: Travere Call Center
- Número de telefone: 1-877-659-5518
- E-mail: medinfo@travere.com
Locais de estudo
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Hamburg, Alemanha
- Ainda não está recrutando
- Universitätsklinikum Hamburg-Eppendorf
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Leipzig, Alemanha
- Ainda não está recrutando
- Universitätsklinikum Leipzig
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Münster, Alemanha
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- Universitätsklinikum Münster
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Riyadh, Arábia Saudita
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- King Abdullah International Medical Research Center
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Riyadh, Arábia Saudita
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- King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
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Adelaide, Austrália
- Recrutamento
- Royal Adelaide Hospital
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Parkville, Austrália
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- Royal Children's Hospital Melbourne
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Westmead, Austrália
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- Westmead Hospital
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Brussels, Bélgica
- Recrutamento
- Cliniques Universitaires Saint-Luc
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Edegem, Bélgica
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- Universitair Ziekenhuis Antwerpen (UZA)
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Doha, Catar
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- Hamad General Hospital
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Doha, Catar
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- Sidra Hospital
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Barcelona, Espanha
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- Hospital Sant Joan de Déu
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Madrid, Espanha
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- Hospital Universitario 12 de Octubre
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Madrid, Espanha
- Recrutamento
- Hospital Universitario Ramón y Cajal
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Santiago de Compostela, Espanha
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- Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
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Seville, Espanha
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- Hospital Universitario Virgen del Rocío
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Arizona
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Phoenix, Arizona, Estados Unidos, 85006
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- Phoenix Children's Hospital
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06519
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- Yale University School of Medicine
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Recrutamento
- Emory University
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Recrutamento
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Maine
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Portland, Maine, Estados Unidos, 04102
- Recrutamento
- Maine Health - Maine Medical Center
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Maryland
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Chevy Chase, Maryland, Estados Unidos, 20815
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- Uncommon Cures
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New York
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New York, New York, Estados Unidos, 10029
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- The Mount Sinai Hospital
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North Carolina
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Morrisville, North Carolina, Estados Unidos, 27560
- Recrutamento
- Science 37 - Virtual Site
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Oregon
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Portland, Oregon, Estados Unidos, 97239
- Ainda não está recrutando
- Oregon Health and Science University
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
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- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Estados Unidos, 15224
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- University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
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Texas
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Dallas, Texas, Estados Unidos, 75390
- Recrutamento
- University of Texas Southwestern Medical Center
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Utah
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Salt Lake City, Utah, Estados Unidos, 84113
- Recrutamento
- Utah Health - The University of Utah Primary Children's Hospital
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Paris, França
- Recrutamento
- Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
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Tours, França
- Recrutamento
- CHRU Hôpitaux de Tours - Hôpital Bretonneau
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Vandœuvre-lès-Nancy, França
- Recrutamento
- Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
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Dublin, Irlanda
- Recrutamento
- Children's Health Ireland (CHI) at Temple Street
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Bari, Itália
- Ainda não está recrutando
- Ospedale Pediatrico Giovanni XXIII
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Genova, Itália
- Ainda não está recrutando
- IRCCS Istituto Giannina Gaslini
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Milan, Itália
- Ainda não está recrutando
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
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Monza, Itália
- Ainda não está recrutando
- Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
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Padova, Itália
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- Azienda Ospedaliera di Padova
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Krakow, Polônia
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- SP ZOZ Szpital Uniwersytecki w Krakowie
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Warsaw, Polônia
- Recrutamento
- Instytut Pomnik-Centrum Zdrowia Dziecka
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Warsaw, Polônia
- Ainda não está recrutando
- Instytut Matki i Dziecka
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Coimbra, Portugal
- Recrutamento
- Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
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Lisbon, Portugal
- Recrutamento
- Unidade Local de Saúde de Santa Maria, EPE - Hospital de Santa Maria
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Porto, Portugal
- Ainda não está recrutando
- Unidade Local de Saúde de São João, EPE - Hospital São João
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Birmingham, Reino Unido
- Recrutamento
- Birmingham Women's and Children's NHS Foundation Trust
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Birmingham, Reino Unido
- Recrutamento
- University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
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London, Reino Unido
- Ainda não está recrutando
- University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
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Salford, Reino Unido
- Recrutamento
- Salford Royal NHS Foundation Trust - Salford Royal Hospital
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Ankara, Turquia (Türkiye)
- Recrutamento
- Gazi University Hospital
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Bornova, Turquia (Türkiye)
- Ainda não está recrutando
- Ege Üniversitesi Hastanesi Bornova
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Istanbul, Turquia (Türkiye)
- Ainda não está recrutando
- Istanbul University Cerrahpasa Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Must be ≥12 to ≤65 years of age, at the time of signing the informed consent
- Must have a diagnosis of classical HCU based on clinical, biochemical, and/or molecular genetic testing
- Plasma tHcy ≥80 µM at Screening visit, with allowance for up to 18 participants who may be enrolled with a Screening plasma tHcy ≥50 to <80 µM
- Participants who can become pregnant must have a negative pregnancy test before starting the study and must use a highly effective form of birth control (less than 1% risk of pregnancy per year) during the study and for at least 4 weeks after the last dose.
- Willing to maintain a generally stable diet for the duration of the study (unless changes are required based on medical/safety reasons)
- Willing to maintain generally stable intake and doses of betaine, pyridoxine, and medical food for the duration of the study (unless changes are required based on medical/safety reasons)
Exclusion Criteria:
- Diagnosis of Marfan syndrome, methylenetetrahydrofolate reductase (MTHFR) deficiency, or disorder of cobalamin metabolism
- Concurrent disease or condition (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease) that would interfere with study participation or safety (excluding complications of HCU).
- History of major thrombotic event (eg, cerebrovascular accident, myocardial infarction, pulmonary embolism) in the previous 6 months.
- Body weight ≥160 kg.
- Use or planned use of any injectable drugs containing PEG (excluding PEG-containing vaccines)
- Any previous exposure to pegtibatinase and/or previous participation in a clinical study that included administration of pegtibatinase or pegtarviliase
- Prior severe immune reaction to a PEG-containing product
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Comparador de Placebo: placebo
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volume-matched saline SC BIW |
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Experimental: pegtibatinase
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Pegtibatinase BIW
Outros nomes:
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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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Change from baseline in plasma tHcy levels - Weeks 6 to 12
Prazo: Weeks 6 - 12
|
Change between baseline and average of 6 to 12 week (6, 8, 10, and 12 week) plasma tHcy levels in participants receiving pegtibatinase vs. placebo. Baseline tHcy level defined as average of Week -3, Week -1, and Day 1 pre-dose plasma tHcy |
Weeks 6 - 12
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change from baseline in plasma tHcy levels - Weeks 16 to 24
Prazo: Weeks 16 - 24
|
Change between baseline and average of 16 to 24 week (16, 20, and 24 week) plasma tHcy levels in participants receiving pegtibatinase vs. placebo. Baseline tHcy level defined as average of Week -3, Week -1, and Day 1 pre-dose plasma tHcy |
Weeks 16 - 24
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Michael Imperiale, MD, Travere Therapeutics, Inc.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças Cerebrais
- Doenças do Sistema Nervoso Central
- Doenças do Sistema Nervoso
- Metabolismo, Erros Inatos
- Doenças Genéticas, Congênitas
- Doenças Metabólicas
- Doenças do Tecido Conjuntivo
- Doenças Cerebrais Metabólicas Inatas
- Doenças Cerebrais Metabólicas
- Metabolismo de Aminoácidos, Erros Inatos
- Hiper-homocisteinemia
- Doenças e Anormalidades Congênitas, Hereditárias e Neonatais
- Doenças Nutricionais e Metabólicas
- Doenças da Pele e do Tecido Conjuntivo
- Homocistinúria
Outros números de identificação do estudo
- TVTX-TVT058-301
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Requests for clinical trial data, including language stating its intended use, should be directed to datarequest@travere.com. If approved, the requested information will be provided to the requestor after signing a data access agreement. Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication. Travere reserves the right to decline or recommend modifications to a request if it does not comply with the data sharing policy or if it is determined that the request is made by a biased source.
Prazo de Compartilhamento de IPD
Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication.
Critérios de acesso de compartilhamento IPD
Requires submission and approval of intended use and a data sharing agreement.
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