Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment (HARMONY)
Studio di fase 3, trattamento a gruppi paralleli, in cieco, randomizzato, controllato con placebo per valutare l'efficacia e la sicurezza della pegtibatinasi somministrata per via sottocutanea in aggiunta allo standard di cura in partecipanti con omocistinuria classica dovuta a deficit di cistationina beta sintasi (HARMONY)
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.
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Tipo di studio
Iscrizione (Stimato)
Iscrizione
Fase
Fase
- Fase 3
Contatti e Sedi
Contatto studio
Contatto studio
- Nome: Travere Call Center
- Numero di telefono: 1-877-659-5518
- Email: medinfo@travere.com
Luoghi di studio
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Riyadh, Arabia Saudita
- Reclutamento
- King Abdullah International Medical Research Center
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Riyadh, Arabia Saudita
- Reclutamento
- King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
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Adelaide, Australia
- Reclutamento
- Royal Adelaide Hospital
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Parkville, Australia
- Reclutamento
- Royal Children's Hospital Melbourne
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Westmead, Australia
- Reclutamento
- Westmead Hospital
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Brussels, Belgio
- Reclutamento
- Cliniques Universitaires Saint-Luc
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Edegem, Belgio
- Reclutamento
- Universitair Ziekenhuis Antwerpen (UZA)
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Paris, Francia
- Reclutamento
- Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
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Tours, Francia
- Reclutamento
- CHRU Hôpitaux de Tours - Hôpital Bretonneau
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Vandœuvre-lès-Nancy, Francia
- Reclutamento
- Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
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Hamburg, Germania
- Non ancora reclutamento
- Universitätsklinikum Hamburg-Eppendorf
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Leipzig, Germania
- Non ancora reclutamento
- Universitätsklinikum Leipzig
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Münster, Germania
- Non ancora reclutamento
- Universitätsklinikum Münster
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Dublin, Irlanda
- Reclutamento
- Children's Health Ireland (CHI) at Temple Street
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Bari, Italia
- Non ancora reclutamento
- Ospedale Pediatrico Giovanni XXIII
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Genova, Italia
- Non ancora reclutamento
- IRCCS Istituto Giannina Gaslini
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Milan, Italia
- Non ancora reclutamento
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
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Monza, Italia
- Non ancora reclutamento
- Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
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Padova, Italia
- Non ancora reclutamento
- Azienda Ospedaliera di Padova
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Krakow, Polonia
- Non ancora reclutamento
- SP ZOZ Szpital Uniwersytecki w Krakowie
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Warsaw, Polonia
- Reclutamento
- Instytut Pomnik-Centrum Zdrowia Dziecka
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Warsaw, Polonia
- Non ancora reclutamento
- Instytut Matki i Dziecka
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Coimbra, Portogallo
- Reclutamento
- Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
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Lisbon, Portogallo
- Reclutamento
- Unidade Local de Saúde de Santa Maria, EPE - Hospital de Santa Maria
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Porto, Portogallo
- Non ancora reclutamento
- Unidade Local de Saúde de São João, EPE - Hospital São João
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Doha, Qatar
- Reclutamento
- Hamad General Hospital
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Doha, Qatar
- Reclutamento
- Sidra Hospital
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Birmingham, Regno Unito
- Reclutamento
- Birmingham Women's and Children's NHS Foundation Trust
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Birmingham, Regno Unito
- Reclutamento
- University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
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London, Regno Unito
- Non ancora reclutamento
- University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
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Salford, Regno Unito
- Reclutamento
- Salford Royal NHS Foundation Trust - Salford Royal Hospital
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Barcelona, Spagna
- Reclutamento
- Hospital Sant Joan de Déu
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Madrid, Spagna
- Reclutamento
- Hospital Universitario 12 de Octubre
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Madrid, Spagna
- Reclutamento
- Hospital Universitario Ramón y Cajal
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Santiago de Compostela, Spagna
- Reclutamento
- Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
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Seville, Spagna
- Reclutamento
- Hospital Universitario Virgen del Rocío
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Arizona
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Phoenix, Arizona, Stati Uniti, 85006
- Reclutamento
- Phoenix Children's Hospital
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Connecticut
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New Haven, Connecticut, Stati Uniti, 06519
- Reclutamento
- Yale University School of Medicine
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Georgia
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Atlanta, Georgia, Stati Uniti, 30322
- Reclutamento
- Emory University
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Illinois
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Chicago, Illinois, Stati Uniti, 60611
- Reclutamento
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Maine
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Portland, Maine, Stati Uniti, 04102
- Reclutamento
- Maine Health - Maine Medical Center
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Maryland
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Chevy Chase, Maryland, Stati Uniti, 20815
- Reclutamento
- Uncommon Cures
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New York
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New York, New York, Stati Uniti, 10029
- Reclutamento
- The Mount Sinai Hospital
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North Carolina
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Morrisville, North Carolina, Stati Uniti, 27560
- Reclutamento
- Science 37 - Virtual Site
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Oregon
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Portland, Oregon, Stati Uniti, 97239
- Non ancora reclutamento
- Oregon Health and Science University
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti, 19104
- Reclutamento
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Stati Uniti, 15224
- Reclutamento
- University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
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Texas
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Dallas, Texas, Stati Uniti, 75390
- Reclutamento
- University of Texas Southwestern Medical Center
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Utah
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Salt Lake City, Utah, Stati Uniti, 84113
- Reclutamento
- Utah Health - The University of Utah Primary Children's Hospital
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Ankara, Turchia (Türkiye)
- Reclutamento
- Gazi University Hospital
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Bornova, Turchia (Türkiye)
- Non ancora reclutamento
- Ege Üniversitesi Hastanesi Bornova
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Istanbul, Turchia (Türkiye)
- Non ancora reclutamento
- Istanbul University Cerrahpasa Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
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Comparatore placebo: placebo
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volume-matched saline SC BIW |
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Sperimentale: pegtibatinasi
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Pegtibatinase BIW
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Change from baseline in plasma tHcy levels - Weeks 6 to 12
Lasso di tempo: Weeks 6 - 12
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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
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Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Change from baseline in plasma tHcy levels - Weeks 16 to 24
Lasso di tempo: 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
|
Collaboratori e investigatori
Sponsor
Sponsor
Investigatori
Investigatori
- Direttore dello studio: Michael Imperiale, MD, Travere Therapeutics, Inc.
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Inizio studio
Completamento primario (Stimato)
Completamento primario
Completamento dello studio (Stimato)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie del cervello
- Malattie del sistema nervoso centrale
- Malattie del sistema nervoso
- Metabolismo, errori congeniti
- Malattie genetiche, congenite
- Malattie metaboliche
- Malattie del tessuto connettivo
- Malattie cerebrali, metaboliche, congenite
- Malattie cerebrali, metaboliche
- Metabolismo degli aminoacidi, errori congeniti
- Iperomocisteinemia
- Malattie e anomalie congenite, ereditarie e neonatali
- Malattie nutrizionali e metaboliche
- Malattie della pelle e del tessuto connettivo
- Omocistinuria
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- TVTX-TVT058-301
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano 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.
Periodo di condivisione 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.
Criteri di accesso alla condivisione IPD
Requires submission and approval of intended use and a data sharing agreement.
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
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