Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment (HARMONY)
En fase 3, parallellgruppebehandling, blindet, randomisert, placebokontrollert studie for å vurdere effektiviteten og sikkerheten til pegtibatinase administrert subkutant i tillegg til standardbehandling hos deltakere med klassisk homocystinuri på grunn av cystationin betasyntase-mangel (HMONY)
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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Antatt)
Fase
- Fase 3
Kontakter og plasseringer
Studiekontakt
- Navn: Travere Call Center
- Telefonnummer: 1-877-659-5518
- E-post: medinfo@travere.com
Studiesteder
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Adelaide, Australia
- Rekruttering
- Royal Adelaide Hospital
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Parkville, Australia
- Rekruttering
- Royal Children's Hospital Melbourne
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Westmead, Australia
- Rekruttering
- Westmead Hospital
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Brussels, Belgia
- Rekruttering
- Cliniques Universitaires Saint-Luc
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Edegem, Belgia
- Rekruttering
- Universitair Ziekenhuis Antwerpen (UZA)
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Arizona
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Phoenix, Arizona, Forente stater, 85006
- Rekruttering
- Phoenix Children's Hospital
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Connecticut
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New Haven, Connecticut, Forente stater, 06519
- Rekruttering
- Yale University School of Medicine
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Rekruttering
- Emory University
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Illinois
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Chicago, Illinois, Forente stater, 60611
- Rekruttering
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Maine
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Portland, Maine, Forente stater, 04102
- Rekruttering
- Maine Health - Maine Medical Center
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Maryland
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Chevy Chase, Maryland, Forente stater, 20815
- Rekruttering
- Uncommon Cures
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New York
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New York, New York, Forente stater, 10029
- Rekruttering
- The Mount Sinai Hospital
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North Carolina
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Morrisville, North Carolina, Forente stater, 27560
- Rekruttering
- Science 37 - Virtual Site
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Oregon
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Portland, Oregon, Forente stater, 97239
- Har ikke rekruttert ennå
- Oregon Health and Science University
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19104
- Rekruttering
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Forente stater, 15224
- Rekruttering
- University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
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Texas
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Dallas, Texas, Forente stater, 75390
- Rekruttering
- University of Texas Southwestern Medical Center
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Utah
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Salt Lake City, Utah, Forente stater, 84113
- Rekruttering
- Utah Health - The University of Utah Primary Children's Hospital
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Paris, Frankrike
- Har ikke rekruttert ennå
- Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
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Tours, Frankrike
- Har ikke rekruttert ennå
- CHRU Hôpitaux de Tours - Hôpital Bretonneau
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Vandœuvre-lès-Nancy, Frankrike
- Har ikke rekruttert ennå
- Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
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Dublin, Irland
- Har ikke rekruttert ennå
- Children's Health Ireland (CHI) at Temple Street
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Bari, Italia
- Har ikke rekruttert ennå
- Ospedale Pediatrico Giovanni XXIII
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Genova, Italia
- Har ikke rekruttert ennå
- IRCCS Istituto Giannina Gaslini
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Milan, Italia
- Har ikke rekruttert ennå
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
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Monza, Italia
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- Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
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Padova, Italia
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- Azienda Ospedaliera di Padova
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Krakow, Polen
- Har ikke rekruttert ennå
- SP ZOZ Szpital Uniwersytecki w Krakowie
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Warsaw, Polen
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- Instytut Matki i Dziecka
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Warsaw, Polen
- Har ikke rekruttert ennå
- Instytut Pomnik-Centrum Zdrowia Dziecka
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Coimbra, Portugal
- Har ikke rekruttert ennå
- Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
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Lisbon, Portugal
- Har ikke rekruttert ennå
- Unidade Local de Saúde de Santa Maria, EPE - Hospital de Santa Maria
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Porto, Portugal
- Har ikke rekruttert ennå
- Unidade Local de Saúde de São João, EPE - Hospital São João
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Doha, Qatar
- Rekruttering
- Hamad General Hospital
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Doha, Qatar
- Rekruttering
- Sidra Hospital
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Riyadh, Saudi-Arabia
- Rekruttering
- King Abdullah International Medical Research Center
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Riyadh, Saudi-Arabia
- Rekruttering
- King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
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Barcelona, Spania
- Rekruttering
- Hospital Sant Joan de Déu
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Madrid, Spania
- Har ikke rekruttert ennå
- Hospital Universitario 12 de Octubre
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Madrid, Spania
- Rekruttering
- Hospital Universitario Ramón y Cajal
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Santiago de Compostela, Spania
- Rekruttering
- Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
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Seville, Spania
- Rekruttering
- Hospital Universitario Virgen del Rocío
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Birmingham, Storbritannia
- Rekruttering
- Birmingham Women's and Children's NHS Foundation Trust
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Birmingham, Storbritannia
- Har ikke rekruttert ennå
- University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
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London, Storbritannia
- Har ikke rekruttert ennå
- University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
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Salford, Storbritannia
- Har ikke rekruttert ennå
- Salford Royal NHS Foundation Trust - Salford Royal Hospital
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Ankara, Tyrkia (Türkiye)
- Har ikke rekruttert ennå
- Gazi University Hospital
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Bornova, Tyrkia (Türkiye)
- Har ikke rekruttert ennå
- Ege Üniversitesi Hastanesi Bornova
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Istanbul, Tyrkia (Türkiye)
- Har ikke rekruttert ennå
- Istanbul University Cerrahpasa Hospital
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Hamburg, Tyskland
- Har ikke rekruttert ennå
- Universitätsklinikum Hamburg-Eppendorf
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Leipzig, Tyskland
- Har ikke rekruttert ennå
- Universitätsklinikum Leipzig
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Münster, Tyskland
- Har ikke rekruttert ennå
- Universitätsklinikum Münster
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Placebo komparator: placebo
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volume-matched saline SC BIW |
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Eksperimentell: pegtibatinase
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Pegtibatinase BIW
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Change from baseline in plasma tHcy levels - Weeks 6 to 12
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Change from baseline in plasma tHcy levels - Weeks 16 to 24
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studieleder: Michael Imperiale, MD, Travere Therapeutics, Inc.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Hjernesykdommer
- Sykdommer i sentralnervesystemet
- Sykdommer i nervesystemet
- Metabolisme, medfødte feil
- Genetiske sykdommer, medfødte
- Metabolske sykdommer
- Bindevevssykdommer
- Hjernesykdommer, metabolske, medfødte
- Hjernesykdommer, metabolske
- Aminosyremetabolisme, medfødte feil
- Hyperhomocysteinemi
- Medfødte, arvelige og neonatale sykdommer og abnormiteter
- Ernæringsmessige og metabolske sykdommer
- Hud- og bindevevssykdommer
- Homocystinuri
Andre studie-ID-numre
- TVTX-TVT058-301
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
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-delingstidsramme
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.
Tilgangskriterier for IPD-deling
Requires submission and approval of intended use and a data sharing agreement.
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