Pegtibatinase as a Treatment for Patients With Classical Homocystinuria (HCU) (Also Known as the COMPOSE Study)

NCT03406611 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CBS-HCY-CT-01
• Study Type: interventional
• Target: 39
• Locations: 3 countries
• Sites: 12

Brief 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. 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.

Conditions

Homocystinuria

Outcome Measures

Primary Outcomes (6)

• Incidence of AEs

  Incidence of AEs (by type, severity and relationship to study drug)

  • 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

  • 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

  • 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.

  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.

  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.

  First dose through End of Treatment (up to Week 32)

Secondary Outcomes (12)

• Changes in pegtibatinase levels

  • 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

  • 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)

  Through double-blind study completion, approximately 10 months per patient

• Changes in Met cycle metabolites levels - Me (Cohorts 1-6 Only)

  Through double-blind study completion, approximately 10 months per patient

• Changes in Met cycle metabolites levels - Cth (Cohorts 1-6 Only)

  Through double-blind study completion, approximately 10 months per patient

Study Arms (3)

Pegtibatinase (Cohort 1-6)

ACTIVE COMPARATOR

Double-Blind Treatment Cohorts (≥12 to ≤65 years)

Drug: Pegtibatinase

Placebo (Cohort 1-6)

PLACEBO COMPARATOR

Double-Blind Treatment Cohorts (≥12 to ≤65 years)

Drug: Placebo

Pegtibatinase (Cohort 7)

EXPERIMENTAL

Pediatric Open-label Treatment Cohort (≥5 to \<12 years)

Drug: Pegtibatinase

Interventions

Pegtibatinase DRUG

Pegtibatinase sterile solution for subcutaneous injection

Also known as: TVT-058, OT-58, PEG modified CBS, PEG htCBS C15S, htCBS C15S ME-200GS

Pegtibatinase (Cohort 1-6); Pegtibatinase (Cohort 7)

Placebo DRUG

Normal saline for subcutaneous injection

Placebo (Cohort 1-6)

Eligibility Criteria

• Age: 5 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Travere Therapeutics, Inc.: lead

Study Sites (12)

Travere Investigational Site

Aurora, Colorado, 80045, United States

COMPLETED

Travere Investigational Site

Miami, Florida, 33136, United States

COMPLETED

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

Travere Investigational Site

Indianapolis, Indiana, 46202, United States

COMPLETED

Travere Investigational Site

Portland, Maine, 04102, United States

COMPLETED

Travere Investigational Site

Boston, Massachusetts, 02115, United States

COMPLETED

The Mount Sinai Hospital

New York, New York, 10029, United States

NOT YET RECRUITING

Travere Investigational Site

New York, New York, 10029, United States

COMPLETED

Science 37 - Virtual Site

Morrisville, North Carolina, 27560, United States

RECRUITING

Travere Investigational Site

Philadelphia, Pennsylvania, 19104, United States

COMPLETED

Hospital Necker-Enfants Malades, Neurologie Pediatrique

Paris, 75015, France

NOT YET RECRUITING

Sidra Medicine

Doha, Qatar

NOT YET RECRUITING

MeSH Terms

Conditions

Homocystinuria

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hyperhomocysteinemia; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Michael Imperiale, MD

  Travere Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Travere Call Center

CONTACT

1-877-659-5518; medinfo@travere.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: January 23, 2018
• Study Start: January 22, 2019
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: 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.
• Access Criteria: Requires submission and approval of intended use and a data sharing agreement.

Locations

US (10); FR (1); QA (1)