NCT03406611 · Travere Therapeutics, Inc.
Pegtibatinase as a Treatment for Patients With Classical Homocystinuria (HCU) (Also Known as the COMPOSE Study)
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Pegtibatinase
Pegtibatinase sterile solution for subcutaneous injection
DRUG
Placebo
Normal saline for subcutaneous injection
Primary outcome measures
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
- 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.
Exclusion criteria
- 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)
- 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.
Where
- Aurora, Colorado
- Miami, Florida
- Chicago, Illinois
- Indianapolis, Indiana
- Portland, Maine
- Boston, Massachusetts
- New York, New York
- Morrisville, North Carolina
- Philadelphia, Pennsylvania
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Aug 10, 2026 · Source of record for eligibility and locations