HomocystinuriaPhase 1/2NCT03406611
Pegtibatinase as a Treatment for Patients With Classical Homocystinuria (HCU) (Also Known as the COMPOSE Study)
A Phase 1/2 study testing Pegtibatinase in people with Homocystinuria, run by Travere Therapeutics, Inc. at 12 sites in 3 countries.
Trial summary
Researchers are looking for a better way to treat people who have classical homocystinuria (HCU), a rare condition that is passed down by parents (or "genetic 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 5 to 65 years
- Conditions the study is for
- Homocystinuria
- What is being tested?
- Pegtibatinase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 22 Jan 2019to Jul 2027
- Phase
- Phase 1/2
- 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
- Age
- Cohort 7 (currently enrolling): ≥5 to <12 years of age.
- Completed Cohorts 1-6: ≥12 to 65 years of age.
- Diagnosis of classical homocystinuria (HCU)
- Cohort 7 (currently enrolling): Diagnosis based on clinical, biochemical, and/or molecular genetic testing.
- Completed Cohorts 1-6: Genetically confirmed cystathionine beta-synthase (CBS)-deficient HCU.
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- Plasma total homocysteine (tHcy)
- Cohort 7 (currently enrolling): Plasma tHcy ≥50 μM at Screening.
- Completed Cohorts 1-6: Plasma tHcy ≥50 μM at Screening and documented historical plasma tHcy ≥80 μM.
- Willing and able (or parent/legal guardian willing and able) to provide informed consent/assent and comply with study procedures.
- Willing to maintain a generally stable standard-of-care treatment regimen, including dietary management and HCU-related therapies, unless changes are medically necessary.
- Participants of childbearing potential must have a negative pregnancy test before study treatment and agree to use protocol-specified contraception, if applicable.
Who cannot join
- Cohort 7 only:
- Diagnosis of Marfan syndrome, methylenetetrahydrofolate reductase (MTHFR) deficiency, or a disorder of cobalamin metabolism.
- History of a major thrombotic event within the previous 6 months.
- Body weight <15 kg.
- All Cohorts:
- Previous treatment with pegtibatinase or pegtarviliase)
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- Participation in a pegtibatinase clinical study.
- Receipt of another investigational drug or investigational medical device within 30 days before Screening or planned use during study participation.
- Use of injectable polyethylene glycol (PEG)-containing medications (other than pegtibatinase or PEG-containing vaccines) within 3 months before Screening or during study participation.
- Known hypersensitivity to pegtibatinase or a history of severe hypersensitivity to a PEG-containing product.
- Active HIV, hepatitis B, or hepatitis C infection.
- History of organ transplantation or immunosuppressive therapy.
- Clinically significant medical conditions that could interfere with study participation or participant safety.
- Pregnant or breastfeeding, or planning to become pregnant during study participation.
- Major surgery planned during the study period.
- Any condition that could prevent the participant from complying with study procedures or completing the study.
Trial locations and contacts
12 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
12 sites in 3 countries
United States10 sites, 3 recruiting
- Completed
Travere Investigational Site
Aurora, Colorado, 80045
- Completed
Travere Investigational Site
Boston, Massachusetts, 02115
- Not yet recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
- Completed
Travere Investigational Site
Indianapolis, Indiana, 46202
- Completed
Travere Investigational Site
Miami, Florida, 33136
- Recruiting
Science 37 - Virtual Site
Morrisville, North Carolina, 27560
- Not yet recruiting
The Mount Sinai Hospital
New York, New York, 10029
- Completed
Travere Investigational Site
New York, New York, 10029
- Completed
Travere Investigational Site
Philadelphia, Pennsylvania, 19104
- Completed
Travere Investigational Site
Portland, Maine, 04102
France1 site, 1 recruiting
- Not yet recruiting
Hospital Necker-Enfants Malades, Neurologie Pediatrique
Paris, 75015
About this study
Official title: A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Effects on Clinical Outcomes of Pegtibatinase (TVT-058) Administered Subcutaneously in Subjects With Cystathionine Beta Synthase-Deficient Homocystinuria (COMPOSE)
Researchers are looking for a better way to treat people who have classical homocystinuria (HCU), a rare condition that is passed down by parents (or "genetic 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 breaks down a substance called homocysteine (from dietary methionine found in protein) and keeps both homocysteine and methionine at normal levels. When this enzyme is not working, homocysteine and methionine build up in the blood, which spreads into different tissues of the body and stops these body tissues from working normally.
People with HCU can experience problems with vision, bones, blood vessels, and cognitive function (the ability to think, learn, and remember). Treatments available for HCU, such as a low protein diet and betaine (Cystadane®), help reduce homocysteine levels. The diet is a low methionine diet and a methionine-free protein supplement (a product that provides extra protein to help meet daily protein needs). These treatments are either not sufficient or are hard to take for many patients.
Read more
Pegtibatinase was developed by scientists to be a version of the CBS enzyme that can be given to people with HCU. Researchers believe that giving pegtibatinase to people with HCU already getting medical treatment (or "standard of care") may reduce their homocysteine levels.
This study is split into 7 different groups getting different amounts of drug. The first 6 groups have already finished the study.
Group 7 plans to enroll participants from the US (virtual and in-person), France, and Qatar.
Read the detailed description
Primary Objective - Cohorts 1-6
Researchers are performing this study to learn if pegtibatinase is safe and tolerable (how it makes participants feel).
Researchers will use medical examination, blood tests, and urine tests to measure side effects (unwanted health problems that may or may not be related to the study treatment), changes in laboratory tests and in the electrical activity of the heart (as measured by electrocardiogram or "ECG"), and if the body makes antibodies to fight against pegtibatinase. Antibodies are proteins that the body makes that may stop pegtibatinase from working or may cause side effects.
Secondary Objectives - Cohorts 1-6
Researchers also want to learn about:
- What are the levels of pegtibatinase in the body after single and repeated doses?
- How does pegtibatinase affect levels of certain substances that are produced when the body breaks down and creates homocysteine?
- What are the effects of pegtibatinase on the eyes, bones, mental health, and cognitive function? Researchers will use blood tests, physical examinations, and questionnaires to answer these questions.
Cohort 7 Objectives
Group 7 is open to children aged 5 to 11 years old (or "pediatric participants") who meet the requirements for the study.
Researchers are performing this part of the study with Group 7 to learn if pegtibatinase is safe and tolerable (how it makes participants feel) and if it increases antibody levels when it is given to children with HCU.
Researchers will use blood tests and physical examinations to measure side effects that happen during the study, changes in laboratory tests, electrical activity of the heart, antibody levels, vital signs, and the number of pediatric participants that have too high or too low levels of methionine. Researchers will use questionnaires to measure the number of pediatric participants that need more protein in their diet.
Researchers are performing this part of the study with Group 7 because they also want to learn about:
- What are the levels of pegtibatinase in the pediatric participant's body after single and repeated doses?
- How does pegtibatinase affect levels of total homocysteine and methionine in the pediatric participant's body? Researchers will use blood tests to answer these questions.
Study Population and Treatments
This study will include children and adults from 5 to 65 years old with HCU. Participants in Groups 1 to 6 were aged 12 to 65 years old, and Group 7 participants will be aged 5 to 11 years old. Participants in the study will take their standard of care treatment.
Groups 1 to 6 have completed this study already. For these groups, 24 participants aged 12 to 65 years old who met the requirements of the study were split into 1 of the 6 groups. For each group, 3 participants were chosen to take pegtibatinase for every 1 participant chosen to take an injection that does not have any medicine in it (or "placebo"). Participants were assigned to pegtibatinase or placebo by chance, like the flip of a coin. This is called "randomization". Neither the researchers nor the participants knew which treatment they were getting until the study was completed. This is known as a "double-blind" approach.
Group 7 is open and will be conducted globally. It will include 10 to 15 pediatric participants aged 5 to 11 years old who meet the requirements of the study. All participants in this group will receive pegtibatinase. All participants will know that this is the treatment that they receive. This is called an "open label" approach. The treatment period will be separated into 3 parts: Part A, Part B, and Part C. Each part will test a different dose of pegtibatinase. After each part, pediatric participants who meet specific requirements will move to the next part. If the pediatric participants do not meet specific requirements to move to the next part, they will have the option to join the ENSEMBLE study (NCT06431893) and continue taking that same dose.
Pegtibatinase or placebo will be given as an injection under the skin (or "subcutaneous injection"). Doses for each group are shown below.
- Group 1: 0.33 mg/kg pegtibatinase or placebo 1 time a week.
- Group 2: 0.66 mg/kg pegtibatinase or placebo 1 time a week.
- Group 3: 1.0 mg/kg pegtibatinase or placebo 1 time a week.
- Group 4: 1.0 mg/kg pegtibatinase or placebo 2 times a week.
- Group 5: 1.5 mg/kg pegtibatinase or placebo 2 times a week.
- Group 6: 2.5 mg/kg pegtibatinase or placebo 2 times a week.
- Group 7:
- Part A: 1.0 mg/kg pegtibatinase 2 times a week for 8 weeks;
- Part B: 1.5 mg/kg pegtibatinase 2 times a week for 8 weeks;
- Part C: 2.5 mg/kg pegtibatinase 2 times a week for 4 weeks.
Study Duration and Visits
Participants in Groups 1 to 6 were in the study for up to 158 weeks, including the screening period of up to 8 weeks, a double-blind treatment period of up to 12 weeks, and an extension period of up to 138 weeks. A continuation study called ENSEMBLE was available to participants. Participants were offered to join the ENSEMBLE study before they finished the extension period of the COMPOSE study.
Pediatric participants in Group 7 may be in the study for up to 42 weeks, including the screening period of up to 10 weeks, open-label treatment period of up to 20 weeks, and up to 12 weeks of additional treatment at the same dose if the ENSEMBLE study is not yet open.
If participants in Group 7 meet all the requirements of the study, they will have up to 53 visits to a study center or at home. If the ENSEMBLE study is not yet open at their site, they can have up to 23 more visits to continue treatment.
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 keep track of any medical problems that a participant has during a study (or "adverse event"). All participants in this study will have regular laboratory tests, health checkups, and site visits to watch for health risks and measure 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
- 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 TVT-058, OT-58, PEG modified CBS, PEG htCBS C15S, htCBS C15S ME-200GS
Pegtibatinase sterile solution for subcutaneous injection
PlaceboDrug
Normal saline for subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Pegtibatinase (Cohort 1-6) | Active comparator | Double-Blind Treatment Cohorts (≥12 to ≤65 years) Receives: Drug: Pegtibatinase |
| Placebo (Cohort 1-6) | Placebo comparator | Double-Blind Treatment Cohorts (≥12 to ≤65 years) Receives: Drug: Placebo |
| Pegtibatinase (Cohort 7) | Experimental | Pediatric Open-label Treatment Cohort (≥5 to <12 years) Receives: Drug: Pegtibatinase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of AEs
Incidence of AEs (by type, severity and relationship to study drug)
Measured: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Anti-pegtibatinase antibodies
Presence and levels of anti-pegtibatinase antibodies in plasma as measured by antibody titers
Measured: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Anti-PEG antibodies
Presence and levels of anti-PEG antibodies in plasma as measured by antibody titers
Measured: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Incidence of hypermethioninemia (Cohort 7 only)
The number and percentage of participants who develop hypermethioninemia during treatment, based on plasma methionine concentrations exceeding the protocol-defined threshold. Participants meeting the protocol-defined threshold may undergo dietary management or study treatment modifications, as appropriate.
Measured: First dose through End of Treatment (up to Week 32)
Incidence of hypomethioninemia (Cohort 7 only)
The number and percentage of participants who develop hypomethioninemia during treatment, based on plasma methionine concentrations below the protocol-defined threshold. Participants meeting the protocol-defined threshold may receive dietary protein supplementation or study treatment modifications, as appropriate.
Measured: First dose through End of Treatment (up to Week 32)
The proportion of participants requiring dietary protein rescue (Cohort 7 only)
The proportion of participants who require initiation of dietary protein supplementation during study treatment to manage protocol-defined low plasma methionine concentrations.
Measured: First dose through End of Treatment (up to Week 32)
Secondary outcomes (12)
Changes in pegtibatinase levels
Changes in pegtibatinase levels following single and repeat administration at specified timepoints
Measured: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Changes in Met cycle metabolites levels - tHcy
Changes in total homocysteine levels in micromoles
Measured: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Changes in Met cycle metabolites levels - total Cys (Cohorts 1-6 Only)
Changes in total cysteine levels in micromoles
Measured: Through double-blind study completion, approximately 10 months per patient
Changes in Met cycle metabolites levels - Me (Cohorts 1-6 Only)
Changes in methionine levels in micromoles
Measured: Through double-blind study completion, approximately 10 months per patient
Changes in Met cycle metabolites levels - Cth (Cohorts 1-6 Only)
Changes in cystathionine levels in micromoles
Measured: Through double-blind study completion, approximately 10 months per patient
Changes in Met cycle metabolites levels - Phe (Cohorts 1-6 Only)
Changes in phenylalanine levels in micromoles
Measured: Through double-blind study completion, approximately 10 months per patient
Descriptive ophthalmology examination findings (Cohorts 1-6 Only)
Comprehensive ophthalmological examination (for each eye: visual acuity [myopia, hyperopia, exotropia], slit lamp examination [ectopic lentis, cataracts, corneal abrasion, and uveitis], retinal examination [retinal degeneration, retinal detachment, retinitis pigmentosa, uveitis)]). Assessment of presence and severity of findings.
Measured: Through double-blind study completion, approximately 10 months per patient
Bone densitometry using dual-energy X-ray absorptionmetry (DEXA) scans (Cohorts 1-6 Only)
Measured: Through double-blind study completion, approximately 10 months per patient
Cognitive assessments using the National Institutes of Health Toolbox Cognition Battery score (Cohorts 1-6 Only)
Measured: Through double-blind study completion, approximately 10 months per patient
Patient Reported Outcome (PRO): Quality of Life in Neurological Disorders [Neuro-QoL] (Cohorts 1-6 Only)
The Quality of Life in Neurological Disorders [Neuro-QoL] includes Anxiety Short Form, Depression Short Form, Satisfaction with Social Roles Short Form, Cognition Function Short Form for 18+ years of age; Anxiety Short Form, Depression Short Form, Social Relations - Interaction with Peers Short Form, and Cognitive Function Short Form for Ages 12 to 17 years old
Measured: Through double-blind study completion, approximately 10 months per patient
Patient Reported Outcome (PRO): Quality of Life by 36-Item Short Form Survey [SF-36] (Cohorts 1-6 Only)
Measured: Through double-blind study completion, approximately 10 months per patient
Patient Reported Outcome (PRO): Quality of Life by EuroQol 5-Dimentional Instrument [EQ 5D] (Cohorts 1-6 Only)
Measured: Through double-blind study completion, approximately 10 months per patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start22 Jan 2019
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Cohorts 1-6 (completed) used a randomized, double-blind, placebo-controlled, parallel-group dose-escalation design. Cohort 7 (recruiting) is an open-label, single-arm pediatric cohort with intra-participant sequential dose escalation from 1.0 mg/kg to 2.5 mg/kg administered twice weekly. Participants who meet protocol-defined criteria progress to the next dose level. Participants who complete treatment or do not meet dose-escalation criteria may transition to the ENSEMBLE long-term extension study or continue treatment until ENSEMBLE is available at their highest tolerated dose.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 39 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
- NCT03406611
- Sponsor's protocol ID
- CBS-HCY-CT-01
- Status last verified
- Jul 2026
- First submitted
- 5 Dec 2017
- Last updated
- 10 Aug 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.
Publications
Ficicioglu C, Thomas JA, Ganesh J, Kudrow D, Lah M, Smith WE, Guner J, McDermott S, Vaidya SA, Wilkening L, Levy HL. Safety and efficacy of pegtibatinase enzyme replacement therapy in adults with classical homocystinuria in the COMPOSE phase 1/2 randomized trial. Genet Med. 2025 Aug;27(8):101456. doi: 10.1016/j.gim.2025.101456. Epub 2025 May 14.
PubMed 40382700
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Effects on Clinical Outcomes of Pegtibatinase (TVT-058) Administered Subcutaneously in Subjects With Cystathionine Beta Synthase-Deficient Homocystinuria (COMPOSE)
- ClinicalTrials.gov ID
- NCT03406611
- Acronym / sponsor ID
- CBS-HCY-CT-01
- Conditions
- Homocystinuria
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- Travere Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Jan 2019 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 23 Jan 2018 (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.
Researchers are looking for a better way to treat people who have classical homocystinuria (HCU), a rare condition that is passed down by parents (or "genetic 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 breaks down a substance called homocysteine (from dietary methionine found in protein) and keeps both homocysteine and methionine at normal levels. When this enzyme is not working, homocysteine and methionine build up in the blood, which spreads into different tissues of the body and stops these body tissues from working normally.
People with HCU can experience problems with vision, bones, blood vessels, and cognitive function (the ability to think, learn, and remember). Treatments available for HCU, such as a low protein diet and betaine (Cystadane®), help reduce homocysteine levels. The diet is a low methionine diet and a methionine-free protein supplement (a product that provides extra protein to help meet daily protein needs). These treatments are either not sufficient or are hard to take for many patients.
Pegtibatinase was developed by scientists to be a version of the CBS enzyme that can be given to people with HCU. Researchers believe that giving pegtibatinase to people with HCU already getting medical treatment (or "standard of care") may reduce their homocysteine levels.
This study is split into 7 different groups getting different amounts of drug. The first 6 groups have already finished the study.
Group 7 plans to enroll participants from the US (virtual and in-person), France, and Qatar.
Detailed description
Primary Objective - Cohorts 1-6
Researchers are performing this study to learn if pegtibatinase is safe and tolerable (how it makes participants feel).
Researchers will use medical examination, blood tests, and urine tests to measure side effects (unwanted health problems that may or may not be related to the study treatment), changes in laboratory tests and in the electrical activity of the heart (as measured by electrocardiogram or "ECG"), and if the body makes antibodies to fight against pegtibatinase. Antibodies are proteins that the body makes that may stop pegtibatinase from working or may cause side effects.
Secondary Objectives - Cohorts 1-6
Researchers also want to learn about:
- What are the levels of pegtibatinase in the body after single and repeated doses?
- How does pegtibatinase affect levels of certain substances that are produced when the body breaks down and creates homocysteine?
- What are the effects of pegtibatinase on the eyes, bones, mental health, and cognitive function? Researchers will use blood tests, physical examinations, and questionnaires to answer these questions.
Cohort 7 Objectives
Group 7 is open to children aged 5 to 11 years old (or "pediatric participants") who meet the requirements for the study.
Researchers are performing this part of the study with Group 7 to learn if pegtibatinase is safe and tolerable (how it makes participants feel) and if it increases antibody levels when it is given to children with HCU.
Researchers will use blood tests and physical examinations to measure side effects that happen during the study, changes in laboratory tests, electrical activity of the heart, antibody levels, vital signs, and the number of pediatric participants that have too high or too low levels of methionine. Researchers will use questionnaires to measure the number of pediatric participants that need more protein in their diet.
Researchers are performing this part of the study with Group 7 because they also want to learn about:
- What are the levels of pegtibatinase in the pediatric participant's body after single and repeated doses?
- How does pegtibatinase affect levels of total homocysteine and methionine in the pediatric participant's body? Researchers will use blood tests to answer these questions.
Study Population and Treatments
This study will include children and adults from 5 to 65 years old with HCU. Participants in Groups 1 to 6 were aged 12 to 65 years old, and Group 7 participants will be aged 5 to 11 years old. Participants in the study will take their standard of care treatment.
Groups 1 to 6 have completed this study already. For these groups, 24 participants aged 12 to 65 years old who met the requirements of the study were split into 1 of the 6 groups. For each group, 3 participants were chosen to take pegtibatinase for every 1 participant chosen to take an injection that does not have any medicine in it (or "placebo"). Participants were assigned to pegtibatinase or placebo by chance, like the flip of a coin. This is called "randomization". Neither the researchers nor the participants knew which treatment they were getting until the study was completed. This is known as a "double-blind" approach.
Group 7 is open and will be conducted globally. It will include 10 to 15 pediatric participants aged 5 to 11 years old who meet the requirements of the study. All participants in this group will receive pegtibatinase. All participants will know that this is the treatment that they receive. This is called an "open label" approach. The treatment period will be separated into 3 parts: Part A, Part B, and Part C. Each part will test a different dose of pegtibatinase. After each part, pediatric participants who meet specific requirements will move to the next part. If the pediatric participants do not meet specific requirements to move to the next part, they will have the option to join the ENSEMBLE study (NCT06431893) and continue taking that same dose.
Pegtibatinase or placebo will be given as an injection under the skin (or "subcutaneous injection"). Doses for each group are shown below.
- Group 1: 0.33 mg/kg pegtibatinase or placebo 1 time a week.
- Group 2: 0.66 mg/kg pegtibatinase or placebo 1 time a week.
- Group 3: 1.0 mg/kg pegtibatinase or placebo 1 time a week.
- Group 4: 1.0 mg/kg pegtibatinase or placebo 2 times a week.
- Group 5: 1.5 mg/kg pegtibatinase or placebo 2 times a week.
- Group 6: 2.5 mg/kg pegtibatinase or placebo 2 times a week.
- Group 7:
- Part A: 1.0 mg/kg pegtibatinase 2 times a week for 8 weeks;
- Part B: 1.5 mg/kg pegtibatinase 2 times a week for 8 weeks;
- Part C: 2.5 mg/kg pegtibatinase 2 times a week for 4 weeks.
Study Duration and Visits
Participants in Groups 1 to 6 were in the study for up to 158 weeks, including the screening period of up to 8 weeks, a double-blind treatment period of up to 12 weeks, and an extension period of up to 138 weeks. A continuation study called ENSEMBLE was available to participants. Participants were offered to join the ENSEMBLE study before they finished the extension period of the COMPOSE study.
Pediatric participants in Group 7 may be in the study for up to 42 weeks, including the screening period of up to 10 weeks, open-label treatment period of up to 20 weeks, and up to 12 weeks of additional treatment at the same dose if the ENSEMBLE study is not yet open.
If participants in Group 7 meet all the requirements of the study, they will have up to 53 visits to a study center or at home. If the ENSEMBLE study is not yet open at their site, they can have up to 23 more visits to continue treatment.
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 keep track of any medical problems that a participant has during a study (or "adverse event"). All participants in this study will have regular laboratory tests, health checkups, and site visits to watch for health risks and measure 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Cohorts 1-6 (completed) used a randomized, double-blind, placebo-controlled, parallel-group dose-escalation design. Cohort 7 (recruiting) is an open-label, single-arm pediatric cohort with intra-participant sequential dose escalation from 1.0 mg/kg to 2.5 mg/kg administered twice weekly. Participants who meet protocol-defined criteria progress to the next dose level. Participants who complete treatment or do not meet dose-escalation criteria may transition to the ENSEMBLE long-term extension study or continue treatment until ENSEMBLE is available at their highest tolerated dose.
| Arm | Type | Receives |
|---|---|---|
| Pegtibatinase (Cohort 1-6) | Active comparator | Drug: PegtibatinaseDouble-Blind Treatment Cohorts (≥12 to ≤65 years) |
| Placebo (Cohort 1-6) | Placebo comparator | Drug: PlaceboDouble-Blind Treatment Cohorts (≥12 to ≤65 years) |
| Pegtibatinase (Cohort 7) | Experimental | Drug: PegtibatinasePediatric Open-label Treatment Cohort (≥5 to <12 years) |
Who may qualify
- Ages
- 5 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Age
- Diagnosis of classical homocystinuria (HCU)
- Plasma total homocysteine (tHcy)
- Willing and able (or parent/legal guardian willing and able) to provide informed consent/assent and comply with study procedures.
- Willing to maintain a generally stable standard-of-care treatment regimen, including dietary management and HCU-related therapies, unless changes are medically necessary.
Key exclusion criteria (16 listed)
- Diagnosis of Marfan syndrome, methylenetetrahydrofolate reductase (MTHFR) deficiency, or a disorder of cobalamin metabolism.
- History of a major thrombotic event within the previous 6 months.
- Body weight <15 kg.
- Previous treatment with pegtibatinase or pegtarviliase)
- Participation in a pegtibatinase clinical study.
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: TVT-058, OT-58, PEG modified CBS, PEG htCBS C15S, htCBS C15S ME-200GSPegtibatinase sterile solution for subcutaneous injection | Drug | Pegtibatinase (Cohort 1-6), Pegtibatinase (Cohort 7) |
| PlaceboNormal saline for subcutaneous injection | Drug | Placebo (Cohort 1-6) |
Primary outcome
Incidence of AEs
Time frame: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Incidence of AEs (by type, severity and relationship to study drug)
Anti-pegtibatinase antibodies
Time frame: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Presence and levels of anti-pegtibatinase antibodies in plasma as measured by antibody titers
Anti-PEG antibodies
Time frame: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Presence and levels of anti-PEG antibodies in plasma as measured by antibody titers
Incidence of hypermethioninemia (Cohort 7 only)
Time frame: First dose through End of Treatment (up to Week 32)
The number and percentage of participants who develop hypermethioninemia during treatment, based on plasma methionine concentrations exceeding the protocol-defined threshold. Participants meeting the protocol-defined threshold may undergo dietary management or study treatment modifications, as appropriate.
Incidence of hypomethioninemia (Cohort 7 only)
Time frame: First dose through End of Treatment (up to Week 32)
The number and percentage of participants who develop hypomethioninemia during treatment, based on plasma methionine concentrations below the protocol-defined threshold. Participants meeting the protocol-defined threshold may receive dietary protein supplementation or study treatment modifications, as appropriate.
The proportion of participants requiring dietary protein rescue (Cohort 7 only)
Time frame: First dose through End of Treatment (up to Week 32)
The proportion of participants who require initiation of dietary protein supplementation during study treatment to manage protocol-defined low plasma methionine concentrations.
12 secondary outcomes
Changes in pegtibatinase levels
Time frame: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Changes in Met cycle metabolites levels - tHcy
Time frame: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
Changes in Met cycle metabolites levels - total Cys (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
Changes in Met cycle metabolites levels - Me (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
Changes in Met cycle metabolites levels - Cth (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
Changes in Met cycle metabolites levels - Phe (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
Descriptive ophthalmology examination findings (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
Bone densitometry using dual-energy X-ray absorptionmetry (DEXA) scans (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
Cognitive assessments using the National Institutes of Health Toolbox Cognition Battery score (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
Patient Reported Outcome (PRO): Quality of Life in Neurological Disorders [Neuro-QoL] (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
Patient Reported Outcome (PRO): Quality of Life by 36-Item Short Form Survey [SF-36] (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
Patient Reported Outcome (PRO): Quality of Life by EuroQol 5-Dimentional Instrument [EQ 5D] (Cohorts 1-6 Only)
Time frame: Through double-blind study completion, approximately 10 months per patient
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 10 Aug 2026.
- Derived from this study: PubMed 40382700Ficicioglu C, Thomas JA, Ganesh J, Kudrow D, Lah M, Smith WE, Guner J, McDermott S, Vaidya SA, Wilkening L, Levy HL. Safety and efficacy of pegtibatinase enzyme replacement therapy in adults with classical homocystinuria in the COMPOSE phase 1/2 randomized trial. Genet Med. 2025 Aug;27(8):101456. doi: 10.1016/j.gim.2025.101456. Epub 2025 May 14.
- 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.
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pegtibatinase in people with Homocystinuria, run by Travere Therapeutics, Inc. at 12 sites in 3 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 12 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, France, Qatar. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Travere Call Center (1-877-659-5518, medinfo@travere.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of AEs (time frame: • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03406611, which also lists 1 linked publication.
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 10 Aug 2026.