HomocystinuriaPhase 3ENSEMBLENCT06431893
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)
A Phase 3 study testing Pegtibatinase in people with Homocystinuria, run by Travere Therapeutics, Inc. at 52 sites in 14 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 5 to 65 years
- Conditions the study is for
- Homocystinuria
- What is being tested?
- Pegtibatinase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 52 sitesin 14 countries
- Study dates
- 30 Apr 2024to Aug 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 5 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Participant permanently discontinued from study intervention treatment in a previous pegtibatinase study due to serious AE (SAE) or intolerance
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
Emory University
Atlanta, Georgia, 30322
Uncommon Cures
Chevy Chase, Maryland, 20815
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Science 37 - Virtual Site
Morrisville, North Carolina, 27560
Yale University School of Medicine
New Haven, Connecticut, 06519
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85006
University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Maine Health Pediatric Specialty Care
Portland, Maine, 04012
Oregon Health and Science University
Portland, Oregon, 97239
Utah Health - The University of Utah Primary Children's Hospital
Salt Lake City, Utah, 84113
Italy5 sites
Ospedale Pediatrico Giovanni XXIII
Bari
IRCCS Istituto Giannina Gaslini
Genova
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
Milan
Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
Monza
Azienda Ospedaliera di Padova
Padova
Spain5 sites
Hospital Sant Joan de Déu
Barcelona
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario Ramón y Cajal
Madrid
Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
Santiago de Compostela
Hospital Universitario Virgen del Rocío
Seville
United Kingdom4 sites
Birmingham Women's and Children's NHS Foundation Trust
Birmingham
University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
Birmingham
University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
London
Salford Royal NHS Foundation Trust - Salford Royal Hospital
Salford
Australia3 sites
Royal Adelaide Hospital
Adelaide
Royal Children's Hospital Melbourne
Parkville
Westmead Hospital
Westmead
France3 sites
Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
Paris
CHRU Hôpitaux de Tours - Hôpital Bretonneau
Tours
Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
Vandœuvre-lès-Nancy
Germany3 sites
Universitätsklinikum Hamburg-Eppendorf
Hamburg
Universitätsklinikum Leipzig
Leipzig
Universitätsklinikum Münster
Münster
Poland3 sites
SP ZOZ Szpital Uniwersytecki w Krakowie
Krakow
Instytut Matki i Dziecka
Warsaw
Instytut Pomnik-Centrum Zdrowia Dziecka
Warsaw
Portugal3 sites
Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
Coimbra
Unidade Local de Saúde de Santa Maria, EPE - Hospital de Santa Maria
Lisbon
Unidade Local de Saúde de São João, EPE - Hospital São João
Porto
Turkey (Türkiye)3 sites
Gazi University Hospital
Ankara
Ege Üniversitesi Hastanesi Bornova
Bornova
Istanbul University Cerrahpasa Hospital
Istanbul
Belgium2 sites
Cliniques Universitaires Saint-Luc
Brussels
Universitair Ziekenhuis Antwerpen (UZA)
Edegem
Saudi Arabia2 sites
King Abdullah International Medical Research Center
Riyadh
King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
Riyadh
About this study
Official title: 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
Read the 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.
- Conditions
- Homocystinuria
- Being tested
- Pegtibatinase
- Keywords
- Classical homocystinuria, HCU, Cystathionine Beta Synthase Deficiency
- 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-58, TVT-058
Pegtibatinase BIW
| Study group | Role | What they receive |
|---|---|---|
| pegtibatinase | Experimental | Not described Receives: Drug: Pegtibatinase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-emergent AEs
Incidence of treatment-emergent AEs
Measured: Week 1 - Week 108
Hypermethioninemia
Incidence of hypermethioninemia
Measured: Week 1 - Week 108
Hypomethioninemia
Incidence of hypomethioninemia
Measured: Week 1 - Week 108
Dietary Protein Rescue
Proportion of participants requiring dietary protein rescue for participants with hypomethioninemia
Measured: Week 1 - Week 108
Secondary outcomes (3)
Maximum Drug Concentration
Pegtibatinase pharmacokinetic parameters at steady state - maximum drug concentration [Cmax]
Measured: Pharmacokinetic Assessment Period - 4 weeks & 8 weeks
Area under the Curve within the Dosing Interval
Pegtibatinase pharmacokinetic parameters at steady state within the - area under the curve within the dosing interval [AUC0-tau]
Measured: Pharmacokinetic Assessment Period - 4 weeks & 8 weeks
Total Homocysteine (tHcy) Levels
Relative and absolute changes from baseline in tHcy levels
Measured: Week 1 - Week 108
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2024
- Study start30 Apr 2024
- Primary completionAug 2030 (estimated)
- Study completionAug 2030 (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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 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
- NCT06431893
- Sponsor's protocol ID
- TVTX-TVT058-302
- Acronym
- ENSEMBLE
- Status last verified
- May 2026
- First submitted
- 8 May 2024
- Last updated
- 28 May 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.
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06431893
- Acronym / sponsor ID
- ENSEMBLE / TVTX-TVT058-302
- Conditions
- Homocystinuria
- Keywords
- Classical homocystinuria, HCU, Cystathionine Beta Synthase Deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Travere Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Apr 2024 (actual)
- Primary completion
- Aug 2030 (estimated)
- Study completion
- Aug 2030 (estimated)
- First posted
- 29 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| pegtibatinase | Experimental | Drug: Pegtibatinase |
Who may qualify
- Ages
- 5 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- Participant permanently discontinued from study intervention treatment in a previous pegtibatinase study due to serious AE (SAE) or intolerance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PegtibatinaseAlso: OT-58, TVT-058Pegtibatinase BIW | Drug | pegtibatinase |
Primary outcome
Treatment-emergent AEs
Time frame: Week 1 - Week 108
Incidence of treatment-emergent AEs
Hypermethioninemia
Time frame: Week 1 - Week 108
Incidence of hypermethioninemia
Hypomethioninemia
Time frame: Week 1 - Week 108
Incidence of hypomethioninemia
Dietary Protein Rescue
Time frame: Week 1 - Week 108
Proportion of participants requiring dietary protein rescue for participants with hypomethioninemia
3 secondary outcomes
Maximum Drug Concentration
Time frame: Pharmacokinetic Assessment Period - 4 weeks & 8 weeks
Area under the Curve within the Dosing Interval
Time frame: Pharmacokinetic Assessment Period - 4 weeks & 8 weeks
Total Homocysteine (tHcy) Levels
Time frame: Week 1 - Week 108
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Imperiale, MD study director
Travere Therapeutics, Inc.
52 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pegtibatinase in people with Homocystinuria, run by Travere Therapeutics, Inc. at 52 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 52 sites in United States, Italy, Spain, United Kingdom, Australia and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-emergent AEs (time frame: Week 1 - Week 108). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026; AzTrials last refreshed its copy on 30 Oct 2026.