A Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥5 to ≤65 Years of Age With Classical Homocystinuria (HCU) (ENSEMBLE) (ENSEMBLE)

May 27, 2026 updated by: Travere Therapeutics, Inc.

An Open-Label, Phase 3 Long-Term Extension (LTE) Study To Assess The Safety, Tolerability, And Efficacy Of Treatment With Pegtibatinase In Participants With Classical Homocystinuria (HCU) Due To Cystathionine Beta Synthase Deficiency (ENSEMBLE)

The goal of this long-term extension (LTE) study is to evaluate the safety and efficacy of pegtibatinase in patients with classical homocystinuria (HCU). Patients who are active in the Phase 1/2 COMPOSE study or those who complete the 24 weeks of blinded treatment in the Phase 3 HARMONY are eligible to participate.

Participants will be in this clinical study for a minimum of 108 weeks including:

  • a treatment period of up to 104 weeks
  • a 4-week safety follow-up period

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Overall Design:

This is a global, multicenter, single-arm, open-label study. Participants who meet all eligibility criteria may transition from other pegtibatinase studies and enroll into this LTE study for long-term safety, efficacy, and clinical assessments of pegtibatinase treatment.

All participants will follow a protocol of self-administration of pegtibatinase unless exempted. During the study, pegtibatinase pharmacokinetic assessments will be conducted. An optional protein tolerance modification (PTM) sub-study will also be conducted for eligible participants.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia
        • Royal Adelaide Hospital
      • Parkville, Australia
        • Royal Children's Hospital Melbourne
      • Westmead, Australia
        • Westmead Hospital
  • Belgium
      • Brussels, Belgium
        • Cliniques Universitaires Saint-Luc
      • Edegem, Belgium
        • Universitair Ziekenhuis Antwerpen (UZA)
  • France
      • Paris, France
        • Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
      • Tours, France
        • CHRU Hôpitaux de Tours - Hôpital Bretonneau
      • Vandœuvre-lès-Nancy, France
        • Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
  • Germany
      • Hamburg, Germany
        • Universitätsklinikum Hamburg-Eppendorf
      • Leipzig, Germany
        • Universitätsklinikum Leipzig
      • Münster, Germany
        • Universitätsklinikum Münster
  • Ireland
      • Dublin, Ireland
        • Children's Health Ireland (CHI) at Temple Street
  • Italy
      • Bari, Italy
        • Ospedale Pediatrico Giovanni XXIII
      • Genova, Italy
        • IRCCS Istituto Giannina Gaslini
      • Milan, Italy
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
      • Monza, Italy
        • Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
      • Padova, Italy
        • Azienda Ospedaliera Di Padova
  • Poland
      • Krakow, Poland
        • SP ZOZ Szpital Uniwersytecki w Krakowie
      • Warsaw, Poland
        • Instytut Matki i Dziecka
      • Warsaw, Poland
        • Instytut Pomnik-Centrum Zdrowia Dziecka
  • Portugal
      • Coimbra, Portugal
        • Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
      • Lisbon, Portugal
        • Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria
      • Porto, Portugal
        • Unidade Local de Saúde de São João, EPE - Hospital São João
  • Qatar
      • Doha, Qatar
        • Hamad General Hospital
      • Doha, Qatar
        • Sidra Hospital
  • Saudi Arabia
      • Riyadh, Saudi Arabia
        • King Abdullah International Medical Research Center
      • Riyadh, Saudi Arabia
        • King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
  • Spain
      • Barcelona, Spain
        • Hospital Sant Joan de Deu
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain
        • Hospital Universitario Ramon y Cajal
      • Santiago de Compostela, Spain
        • Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
      • Seville, Spain
        • Hospital Universitario Virgen Del Rocio
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye)
        • Gazi University Hospital
      • Bornova, Turkey (Türkiye)
        • Ege Üniversitesi Hastanesi Bornova
      • Istanbul, Turkey (Türkiye)
        • Istanbul University Cerrahpasa Hospital
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Women's and Children's NHS Foundation Trust
      • Birmingham, United Kingdom
        • University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
      • London, United Kingdom
        • University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
      • Salford, United Kingdom
        • Salford Royal NHS Foundation Trust - Salford Royal Hospital
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Phoenix Children's Hospital
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale University School of Medicine
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Maine
      • Portland, Maine, United States, 04012
        • Maine Health Pediatric Specialty Care
    • Maryland
      • Chevy Chase, Maryland, United States, 20815
        • Uncommon Cures
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai
    • North Carolina
      • Morrisville, North Carolina, United States, 27560
        • Science 37 - Virtual Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Utah Health - The University of Utah Primary Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants active in the COMPOSE study or who completed the 24-week blinded period on study intervention (pegtibatinase or placebo) in the Phase 3 HARMONY study

Exclusion Criteria:

  • Participant permanently discontinued from study intervention treatment in a previous pegtibatinase study due to serious AE (SAE) or intolerance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: pegtibatinase
Drug: Pegtibatinase
Pegtibatinase BIW
Other Names:
  • TVT-058
  • OT-58

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment-emergent AEs
Time Frame: Week 1 - Week 108
Incidence of treatment-emergent AEs
Week 1 - Week 108
Hypermethioninemia
Time Frame: Week 1 - Week 108
Incidence of hypermethioninemia
Week 1 - Week 108
Hypomethioninemia
Time Frame: Week 1 - Week 108
Incidence of hypomethioninemia
Week 1 - Week 108
Dietary Protein Rescue
Time Frame: Week 1 - Week 108
Proportion of participants requiring dietary protein rescue for participants with hypomethioninemia
Week 1 - Week 108

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Homocysteine (tHcy) Levels
Time Frame: Week 1 - Week 108
Relative and absolute changes from baseline in tHcy levels
Week 1 - Week 108
Maximum Drug Concentration
Time Frame: Pharmacokinetic Assessment Period - 4 weeks & 8 weeks
Pegtibatinase pharmacokinetic parameters at steady state - maximum drug concentration [Cmax]
Pharmacokinetic Assessment Period - 4 weeks & 8 weeks
Area under the Curve within the Dosing Interval
Time Frame: Pharmacokinetic Assessment Period - 4 weeks & 8 weeks
Pegtibatinase pharmacokinetic parameters at steady state within the - area under the curve within the dosing interval [AUC0-tau]
Pharmacokinetic Assessment Period - 4 weeks & 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Travere Therapeutics, Inc.

Investigators

  • Study Director: Michael Imperiale, MD, Travere Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2024

Primary Completion (Estimated)

August 1, 2030

Study Completion (Estimated)

August 1, 2030

Study Registration Dates

First Submitted

May 8, 2024

First Submitted That Met QC Criteria

May 21, 2024

First Posted (Actual)

May 29, 2024

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 27, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TVTX-TVT058-302

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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 Time Frame

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 Access Criteria

Requires submission and approval of intended use and a data sharing agreement.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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