Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment (HARMONY)

November 5, 2026 updated by: Travere Therapeutics, Inc.

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
      • Adelaide, Australia
        • Recruiting
        • Royal Adelaide Hospital
      • Parkville, Australia
        • Recruiting
        • Royal Children's Hospital Melbourne
      • Westmead, Australia
        • Recruiting
        • Westmead Hospital
  • Belgium
      • Brussels, Belgium
        • Recruiting
        • Cliniques Universitaires Saint-Luc
      • Edegem, Belgium
        • Recruiting
        • Universitair Ziekenhuis Antwerpen (UZA)
  • France
      • Paris, France
        • Recruiting
        • Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
      • Tours, France
        • Recruiting
        • CHRU Hôpitaux de Tours - Hôpital Bretonneau
      • Vandœuvre-lès-Nancy, France
        • Recruiting
        • Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
  • Germany
      • Hamburg, Germany
        • Not yet recruiting
        • Universitätsklinikum Hamburg-Eppendorf
      • Leipzig, Germany
        • Not yet recruiting
        • Universitätsklinikum Leipzig
      • Münster, Germany
        • Not yet recruiting
        • Universitätsklinikum Münster
  • Ireland
      • Dublin, Ireland
        • 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
        • Recruiting
        • Instytut Pomnik-Centrum Zdrowia Dziecka
      • Warsaw, Poland
        • Not yet recruiting
        • Instytut Matki i Dziecka
  • Portugal
      • Coimbra, Portugal
        • Recruiting
        • Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
      • Lisbon, Portugal
        • Recruiting
        • Unidade Local de Saúde 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
        • Recruiting
        • Hamad General Hospital
      • Doha, Qatar
        • Recruiting
        • Sidra Hospital
  • Saudi Arabia
      • Riyadh, Saudi Arabia
        • Recruiting
        • King Abdullah International Medical Research Center
      • Riyadh, Saudi Arabia
        • Recruiting
        • King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Sant Joan de Déu
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario Ramón y Cajal
      • Santiago de Compostela, Spain
        • Recruiting
        • Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
      • Seville, Spain
        • Recruiting
        • Hospital Universitario Virgen del Rocío
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye)
        • 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
        • Recruiting
        • Birmingham Women's and Children's NHS Foundation Trust
      • Birmingham, United Kingdom
        • 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
        • Recruiting
        • Salford Royal NHS Foundation Trust - Salford Royal Hospital
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • 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
        • 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
        • Recruiting
        • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from baseline in plasma tHcy levels - Weeks 6 to 12
Time Frame: Weeks 6 - 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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline in plasma tHcy levels - Weeks 16 to 24
Time Frame: 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

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Travere Therapeutics, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 28, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 30, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 30, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 7, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 9, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

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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