A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care Treatment (HARMONY)

A Phase 3, Parallel-Group Treatment, Blinded, Randomized, Placebo-Controlled Study To Assess The Efficacy And Safety Of Pegtibatinase Administered Subcutaneously In Addition To Standard Of Care In Participants With Classical Homocystinuria Due To Cystathionine Beta Synthase Deficiency (HARMONY)

The purpose of this study is to measure efficacy and safety of pegtibatinase treatment compared with placebo in participants with classical HCU receiving standard of care. Study details include:

• Total Study duration: up to 38 weeks

• Screening:

  • Initial Screening duration: up to 4 weeks
  • Pre-treatment Diet Standardization Period duration: up to 6 weeks

• Blinded Treatment Duration: 24 weeks

  • 2-week blinded dose titration period
  • 22-week blinded assessment period
• Safety Follow-Up: 4 weeks after last dose (as applicable for those not enrolling in the long term extension study, ENSEMBLE)

Study Overview

• Status: Recruiting
• Conditions: Homocystinuria
• Intervention / Treatment: Other: Placebo; Drug: Pegtibatinase

Detailed Description

Overall Design:

This global Phase 3 multi-center, multi-national, randomized, blinded, placebo-controlled study will be conducted in participants with classical CBS deficient HCU receiving standard of care who continue to have tHcy levels ≥50 μM. The total study duration will be up to 38 weeks. Approximately 70 participants (35 per arm) will be randomized to receive active drug or placebo (1:1 allocation).

Screening:

Participants will enter into a 2-phase Screening period of up to 10 weeks:

1. Initial Screening: up to 4-week period during which participants will be assessed for eligibility
2. Pre-treatment Diet Standardization Period (DSP): After meeting initial eligibility criteria, participants will begin a pre treatment DSP of up to 6 weeks. The DSP is intended to help minimize variability in protein intake and supplements throughout the randomized portion of the study.

The baseline diet and compliance with HCU-related treatments will be recorded by the dietitian using the HCU-specific diet monitoring tool, called SING (Simplified Ingested Nutrients Guide). The baseline diet and treatment compliance will be used as a reference for future evaluation of daily intact protein intake (DIPI) and HCU treatments.

Blinded Treatment Period:

During the 24-week blinded treatment period, study visits will occur at regular intervals including home visits for study drug administration. Some study visits may be conducted remotely. Dietary protein intake and compliance with HCU treatments will continue to be monitored and recorded to ensure a stable diet and HCU treatment compliance.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Travere Call Center; Phone Number: 1-877-659-5518; Email: medinfo@travere.com

Study Locations

• Australia
  • Adelaide, Australia
    • Not yet recruiting
    • Royal Adelaide Hospital
  • Parkville, Australia
    • Not yet recruiting
    • Royal Children's Hospital Melbourne
  • Westmead, Australia
    • Not yet recruiting
    • Westmead Hospital
• Belgium
  • Brussels, Belgium
    • Not yet recruiting
    • Cliniques Universitaires Saint-luc
  • Edegem, Belgium
    • Not yet recruiting
    • Universitair Ziekenhuis Antwerpen (UZA)
• France
  • Paris, France
    • Not yet recruiting
    • Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
  • Tours, France
    • Not yet recruiting
    • CHRU Hôpitaux de Tours - Hôpital Bretonneau
  • Vandœuvre-lès-Nancy, France
    • Not yet recruiting
    • Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
• Germany
  • Hamburg, Germany
    • Not yet recruiting
    • Universitatsklinikum Hamburg-Eppendorf
  • Leipzig, Germany
    • Not yet recruiting
    • Universitätsklinikum Leipzig
  • Münster, Germany
    • Not yet recruiting
    • Universitatsklinikum Munster
• Ireland
  • Dublin, Ireland
    • Not yet recruiting
    • Children's Health Ireland (CHI) at Temple Street
• Italy
  • Bari, Italy
    • Not yet recruiting
    • Ospedale Pediatrico Giovanni XXIII
  • Genova, Italy
    • Not yet recruiting
    • IRCCS Istituto Giannina Gaslini
  • Milan, Italy
    • Not yet recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
  • Monza, Italy
    • Not yet recruiting
    • Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
  • Padova, Italy
    • Not yet recruiting
    • Azienda Ospedaliera di Padova
• Poland
  • Krakow, Poland
    • Not yet recruiting
    • SP ZOZ Szpital Uniwersytecki w Krakowie
  • Warsaw, Poland
    • Not yet recruiting
    • Instytut Matki i Dziecka
  • Warsaw, Poland
    • Not yet recruiting
    • Instytut Pomnik-Centrum Zdrowia Dziecka
• Portugal
  • Coimbra, Portugal
    • Not yet recruiting
    • Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
  • Lisbon, Portugal
    • Not yet recruiting
    • Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria
  • Porto, Portugal
    • Not yet recruiting
    • Unidade Local de Saúde de São João, EPE - Hospital São João
• Qatar
  • Doha, Qatar
    • Not yet recruiting
    • Hamad General Hospital
  • Doha, Qatar
    • Not yet recruiting
    • Sidra Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • Not yet recruiting
    • King Abdullah International Medical Research Center
  • Riyadh, Saudi Arabia
    • Not yet recruiting
    • King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
• Spain
  • Barcelona, Spain
    • Not yet recruiting
    • Hospital Sant Joan de Déu
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario Ramon y Cajal
  • Santiago de Compostela, Spain
    • Not yet recruiting
    • Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
  • Seville, Spain
    • Not yet recruiting
    • Hospital Universitario Virgen del Rocio
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye)
    • Not yet recruiting
    • Gazi University Hospital
  • Bornova, Turkey (Türkiye)
    • Not yet recruiting
    • Ege Üniversitesi Hastanesi Bornova
  • Istanbul, Turkey (Türkiye)
    • Not yet recruiting
    • Istanbul University Cerrahpasa Hospital
• United Kingdom
  • Birmingham, United Kingdom
    • Not yet recruiting
    • Birmingham Women's and Children's NHS Foundation Trust
  • Birmingham, United Kingdom
    • Not yet recruiting
    • University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
  • London, United Kingdom
    • Not yet recruiting
    • University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
  • Salford, United Kingdom
    • Not yet recruiting
    • Salford Royal NHS Foundation Trust - Salford Royal Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Not yet recruiting
      • Phoenix Children's Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale University School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Maine
    • Portland, Maine, United States, 04102
      • Recruiting
      • Maine Health - Maine Medical Center
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Recruiting
      • Uncommon Cures
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • The Mount Sinai Hospital
  • North Carolina
    • Morrisville, North Carolina, United States, 27560
      • Recruiting
      • Science 37 - Virtual Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Not yet recruiting
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Not yet recruiting
      • Utah Health - The University of Utah Primary Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Other: Placebo; volume-matched saline SC BIW
Experimental: pegtibatinase	Drug: Pegtibatinase; Pegtibatinase BIW; Other Names: TVT-058; OT-058

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in plasma tHcy levels - Weeks 6 to 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in plasma tHcy levels - Weeks 16 to 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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HCU; cystathionine beta synthase deficiency; Classical Homocystinuria
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Connective Tissue Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Hyperhomocysteinemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Homocystinuria
• Other Study ID Numbers: TVTX-TVT058-301

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