Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment (HARMONY)
Eine verblindete, randomisierte, placebokontrollierte Parallelgruppenbehandlung der Phase 3 zur Bewertung der Wirksamkeit und Sicherheit von subkutan verabreichter Pegtibatinase zusätzlich zur Standardbehandlung bei Teilnehmern mit klassischer Homocystinurie aufgrund eines Cystathionin-Beta-Synthase-Mangels (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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 3
Kontakte und Standorte
Studienkontakt
- Name: Travere Call Center
- Telefonnummer: 1-877-659-5518
- E-Mail: medinfo@travere.com
Studienorte
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Adelaide, Australien
- Rekrutierung
- Royal Adelaide Hospital
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Parkville, Australien
- Rekrutierung
- Royal Children's Hospital Melbourne
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Westmead, Australien
- Rekrutierung
- Westmead Hospital
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Brussels, Belgien
- Rekrutierung
- Cliniques Universitaires Saint-Luc
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Edegem, Belgien
- Rekrutierung
- Universitair Ziekenhuis Antwerpen (UZA)
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Hamburg, Deutschland
- Noch keine Rekrutierung
- Universitätsklinikum Hamburg-Eppendorf
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Leipzig, Deutschland
- Noch keine Rekrutierung
- Universitätsklinikum Leipzig
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Münster, Deutschland
- Noch keine Rekrutierung
- Universitätsklinikum Münster
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Paris, Frankreich
- Noch keine Rekrutierung
- Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
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Tours, Frankreich
- Noch keine Rekrutierung
- CHRU Hôpitaux de Tours - Hôpital Bretonneau
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Vandœuvre-lès-Nancy, Frankreich
- Noch keine Rekrutierung
- Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
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Dublin, Irland
- Noch keine Rekrutierung
- Children's Health Ireland (CHI) at Temple Street
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Bari, Italien
- Noch keine Rekrutierung
- Ospedale Pediatrico Giovanni XXIII
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Genova, Italien
- Noch keine Rekrutierung
- IRCCS Istituto Giannina Gaslini
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Milan, Italien
- Noch keine Rekrutierung
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
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Monza, Italien
- Noch keine Rekrutierung
- Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
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Padova, Italien
- Noch keine Rekrutierung
- Azienda Ospedaliera di Padova
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Doha, Katar
- Rekrutierung
- Hamad General Hospital
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Doha, Katar
- Rekrutierung
- Sidra Hospital
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Krakow, Polen
- Noch keine Rekrutierung
- SP ZOZ Szpital Uniwersytecki w Krakowie
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Warsaw, Polen
- Noch keine Rekrutierung
- Instytut Matki i Dziecka
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Warsaw, Polen
- Noch keine Rekrutierung
- Instytut Pomnik-Centrum Zdrowia Dziecka
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Coimbra, Portugal
- Noch keine Rekrutierung
- Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
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Lisbon, Portugal
- Noch keine Rekrutierung
- Unidade Local de Saúde de Santa Maria, EPE - Hospital de Santa Maria
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Porto, Portugal
- Noch keine Rekrutierung
- Unidade Local de Saúde de São João, EPE - Hospital São João
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Riyadh, Saudi-Arabien
- Rekrutierung
- King Abdullah International Medical Research Center
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Riyadh, Saudi-Arabien
- Rekrutierung
- King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
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Barcelona, Spanien
- Rekrutierung
- Hospital Sant Joan de Déu
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Madrid, Spanien
- Noch keine Rekrutierung
- Hospital Universitario 12 de Octubre
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Madrid, Spanien
- Rekrutierung
- Hospital Universitario Ramón y Cajal
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Santiago de Compostela, Spanien
- Rekrutierung
- Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
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Seville, Spanien
- Rekrutierung
- Hospital Universitario Virgen del Rocío
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Ankara, Türkei (türkiye)
- Noch keine Rekrutierung
- Gazi University Hospital
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Bornova, Türkei (türkiye)
- Noch keine Rekrutierung
- Ege Üniversitesi Hastanesi Bornova
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Istanbul, Türkei (türkiye)
- Noch keine Rekrutierung
- Istanbul University Cerrahpasa Hospital
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Arizona
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Phoenix, Arizona, Vereinigte Staaten, 85006
- Rekrutierung
- Phoenix Children's Hospital
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Connecticut
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New Haven, Connecticut, Vereinigte Staaten, 06519
- Rekrutierung
- Yale University School of Medicine
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Georgia
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Atlanta, Georgia, Vereinigte Staaten, 30322
- Rekrutierung
- Emory University
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Illinois
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Chicago, Illinois, Vereinigte Staaten, 60611
- Rekrutierung
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Maine
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Portland, Maine, Vereinigte Staaten, 04102
- Rekrutierung
- Maine Health - Maine Medical Center
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Maryland
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Chevy Chase, Maryland, Vereinigte Staaten, 20815
- Rekrutierung
- Uncommon Cures
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New York
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New York, New York, Vereinigte Staaten, 10029
- Rekrutierung
- The Mount Sinai Hospital
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North Carolina
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Morrisville, North Carolina, Vereinigte Staaten, 27560
- Rekrutierung
- Science 37 - Virtual Site
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Oregon
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Portland, Oregon, Vereinigte Staaten, 97239
- Noch keine Rekrutierung
- Oregon Health and Science University
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Pennsylvania
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Philadelphia, Pennsylvania, Vereinigte Staaten, 19104
- Rekrutierung
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Vereinigte Staaten, 15224
- Rekrutierung
- University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
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Texas
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Dallas, Texas, Vereinigte Staaten, 75390
- Rekrutierung
- University of Texas Southwestern Medical Center
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Utah
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Salt Lake City, Utah, Vereinigte Staaten, 84113
- Rekrutierung
- Utah Health - The University of Utah Primary Children's Hospital
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Birmingham, Vereinigtes Königreich
- Rekrutierung
- Birmingham Women's and Children's NHS Foundation Trust
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Birmingham, Vereinigtes Königreich
- Noch keine Rekrutierung
- University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
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London, Vereinigtes Königreich
- Noch keine Rekrutierung
- University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
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Salford, Vereinigtes Königreich
- Noch keine Rekrutierung
- Salford Royal NHS Foundation Trust - Salford Royal Hospital
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Placebo-Komparator: Placebo
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volume-matched saline SC BIW |
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Experimental: Pegtibatinase
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Pegtibatinase BIW
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Change from baseline in plasma tHcy levels - Weeks 6 to 12
Zeitfenster: 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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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Change from baseline in plasma tHcy levels - Weeks 16 to 24
Zeitfenster: 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
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Studienleiter: Michael Imperiale, MD, Travere Therapeutics, Inc.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Gehirns
- Erkrankungen des zentralen Nervensystems
- Erkrankungen des Nervensystems
- Stoffwechsel, angeborene Fehler
- Genetische Krankheiten, angeboren
- Stoffwechselerkrankungen
- Bindegewebserkrankungen
- Gehirnerkrankungen, Stoffwechselerkrankungen, angeboren
- Gehirnerkrankungen, Stoffwechsel
- Aminosäurestoffwechsel, angeborene Fehler
- Hyperhomocysteinämie
- Angeborene, erbliche und neonatale Krankheiten und Anomalien
- Ernährungs- und Stoffwechselerkrankungen
- Haut- und Bindegewebserkrankungen
- Homocystinurie
Andere Studien-ID-Nummern
- TVTX-TVT058-301
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
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.
IPD-Sharing-Zeitrahmen
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.
IPD-Sharing-Zugriffskriterien
Requires submission and approval of intended use and a data sharing agreement.
Arzneimittel- und Geräteinformationen, Studienunterlagen
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Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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