A Phase 1/2 interventional study of Pegtibatinase and Placebo in Homocystinuria, sponsored by Travere Therapeutics, Inc.. Recruiting at 12 sites in 3 countries. Open to participants aged 5 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-08-10.
Sponsored by Travere Therapeutics, Inc. · Phase 1/2, Interventional, and Treatment
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.
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:
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:
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.
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:
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.
Age
Diagnosis of classical homocystinuria (HCU)
Plasma total homocysteine (tHcy)
Exclusion Criteria:
Cohort 7 only:
All Cohorts:
Double-Blind Treatment Cohorts (≥12 to ≤65 years)
Drug: Pegtibatinase
Double-Blind Treatment Cohorts (≥12 to ≤65 years)
Drug: Placebo
Pediatric Open-label Treatment Cohort (≥5 to \<12 years)
Drug: Pegtibatinase
Pegtibatinase sterile solution for subcutaneous injection
Also known as: TVT-058, OT-58, PEG modified CBS, PEG htCBS C15S, htCBS C15S ME-200GS
Normal saline for subcutaneous injection
Incidence of AEs
Incidence of AEs (by type, severity and relationship to study drug)
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)
Anti-pegtibatinase antibodies
Presence and levels of anti-pegtibatinase antibodies in plasma as measured by antibody titers
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)
Anti-PEG antibodies
Presence and levels of anti-PEG antibodies in plasma as measured by antibody titers
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 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.
Time frame: 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.
Time frame: 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.
Time frame: First dose through End of Treatment (up to Week 32)
Changes in pegtibatinase levels
Changes in pegtibatinase levels following single and repeat administration at specified timepoints
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
Changes in total homocysteine levels in micromoles
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)
Changes in total cysteine levels in micromoles
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
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)
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
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
Plan to share: 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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Homocystinuria
Travere Therapeutics, Inc.