HomocystinuriaPhase 3HARMONYNCT06247085
Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment
A Phase 3 study testing Pegtibatinase in people with Homocystinuria, run by Travere Therapeutics, Inc. at 52 sites in 14 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Homocystinuria
- What is being tested?
- Pegtibatinase
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 52 sitesin 14 countries
- Study dates
- 28 Dec 2023to Sep 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
52 sites in 14 countries. Contact the study team or a site near you to ask about taking part.
52 sites in 14 countries
United States13 sites, 13 recruiting
- Recruiting
Emory University
Atlanta, Georgia, 30322
- Recruiting
Uncommon Cures
Chevy Chase, Maryland, 20815
- Recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
- Recruiting
Science 37 - Virtual Site
Morrisville, North Carolina, 27560
- Recruiting
Yale University School of Medicine
New Haven, Connecticut, 06519
- Recruiting
The Mount Sinai Hospital
New York, New York, 10029
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
- Recruiting
Phoenix Children's Hospital
Phoenix, Arizona, 85006
- Recruiting
University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
- Recruiting
Maine Health - Maine Medical Center
Portland, Maine, 04102
- Not yet recruiting
Oregon Health and Science University
Portland, Oregon, 97239
- Recruiting
Utah Health - The University of Utah Primary Children's Hospital
Salt Lake City, Utah, 84113
Italy5 sites, 5 recruiting
- Not yet recruiting
Ospedale Pediatrico Giovanni XXIII
Bari
- Not yet recruiting
IRCCS Istituto Giannina Gaslini
Genova
- Not yet recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
Milan
- Not yet recruiting
Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
Monza
- Not yet recruiting
Azienda Ospedaliera di Padova
Padova
Spain5 sites, 5 recruiting
- Recruiting
Hospital Sant Joan de Déu
Barcelona
- Not yet recruiting
Hospital Universitario 12 de Octubre
Madrid
- Recruiting
Hospital Universitario Ramón y Cajal
Madrid
- Recruiting
Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
Santiago de Compostela
- Recruiting
Hospital Universitario Virgen del Rocío
Seville
United Kingdom4 sites, 4 recruiting
- Recruiting
Birmingham Women's and Children's NHS Foundation Trust
Birmingham
- Not yet recruiting
University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
Birmingham
- Not yet recruiting
University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
London
- Not yet recruiting
Salford Royal NHS Foundation Trust - Salford Royal Hospital
Salford
Australia3 sites, 3 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide
- Recruiting
Royal Children's Hospital Melbourne
Parkville
- Recruiting
Westmead Hospital
Westmead
France3 sites, 3 recruiting
- Not yet recruiting
Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
Paris
- Not yet recruiting
CHRU Hôpitaux de Tours - Hôpital Bretonneau
Tours
- Not yet recruiting
Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
Vandœuvre-lès-Nancy
Germany3 sites, 3 recruiting
- Not yet recruiting
Universitätsklinikum Hamburg-Eppendorf
Hamburg
- Not yet recruiting
Universitätsklinikum Leipzig
Leipzig
- Not yet recruiting
Universitätsklinikum Münster
Münster
Poland3 sites, 3 recruiting
- Not yet recruiting
SP ZOZ Szpital Uniwersytecki w Krakowie
Krakow
- Not yet recruiting
Instytut Matki i Dziecka
Warsaw
- Not yet recruiting
Instytut Pomnik-Centrum Zdrowia Dziecka
Warsaw
Portugal3 sites, 3 recruiting
- Not yet recruiting
Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
Coimbra
- Not yet recruiting
Unidade Local de Saúde de Santa Maria, EPE - Hospital de Santa Maria
Lisbon
- Not yet recruiting
Unidade Local de Saúde de São João, EPE - Hospital São João
Porto
Turkey (Türkiye)3 sites, 3 recruiting
- Not yet recruiting
Gazi University Hospital
Ankara
- Not yet recruiting
Ege Üniversitesi Hastanesi Bornova
Bornova
- Not yet recruiting
Istanbul University Cerrahpasa Hospital
Istanbul
Belgium2 sites, 2 recruiting
- Recruiting
Cliniques Universitaires Saint-Luc
Brussels
- Recruiting
Universitair Ziekenhuis Antwerpen (UZA)
Edegem
Qatar2 sites, 2 recruiting
- Recruiting
Hamad General Hospital
Doha
- Recruiting
Sidra Hospital
Doha
Saudi Arabia2 sites, 2 recruiting
- Recruiting
King Abdullah International Medical Research Center
Riyadh
- Recruiting
King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
Riyadh
Ireland1 site, 1 recruiting
- Not yet recruiting
Children's Health Ireland (CHI) at Temple Street
Dublin
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Homocystinuria
- Being tested
- Pegtibatinase, Placebo
- Keywords
- HCU, cystathionine beta synthase deficiency, Classical Homocystinuria
- Medical subject headings
- Homocystinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegtibatinaseDrug
Also called OT-058, TVT-058
Pegtibatinase BIW
PlaceboOther
volume-matched saline SC BIW
| Study group | Role | What they receive |
|---|---|---|
| pegtibatinase | Experimental | Not described Receives: Drug: Pegtibatinase |
| placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Weeks 6 - 12
Secondary outcomes (1)
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
Measured: Weeks 16 - 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2024
- Study start28 Dec 2023
- Primary completionAug 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HomocystinuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Travere Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Imperiale, MD, Study director, Travere Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06247085
- Sponsor's protocol ID
- TVTX-TVT058-301
- Acronym
- HARMONY
- Status last verified
- Oct 2026
- First submitted
- 30 Jan 2024
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.