Pegtibatinase As an Enzyme Therapy for Patients with Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency (COMPOSE)

NCT03406611 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CBS-HCY-CT-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 8

Brief Summary

Homocystinuria caused by Cystathionine Beta-Synthase (CBS) Deficiency is a rare autosomal-recessive metabolic condition characterized by an excess of homocysteine (Hcy) in the plasma, tissues and urine. It is due to reduced or absent activity of the CBS enzyme, and is also known as classical homocystinuria. The symptoms associated with homocystinuria are variable in severity and time of onset across patients. Some affected individuals may have mild signs of the disorder; others may have multi-systemic involvement including potentially life-threatening complications. Homocystinuria can affect many different organ systems of the body; the four most commonly involved are the eyes, central nervous system, skeleton, and the vascular system. The current approaches to treatment of homocystinuria patients include a highly restrictive diet and use of dietary supplements. Lifetime compliance with this diet is poor. Pegtibatinase (TVT-058) represents a novel therapeutic approach that incorporates the use of a modified version of the native, human CBS (hCBS) enzyme. The goal of treatment is to introduce the CBS enzyme into circulation, resulting in reduced Hcy levels, increased cystathionine (Cth) and cysteine (Cys) levels.

Conditions

Homocystinuria

Outcome Measures

Primary Outcomes (3)

• Incidence of AEs

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

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

• Anti-pegtibatinase antibodies

  Presence and levels of anti-pegtibatinase antibodies in plasma as measured by antibody titers

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

• Anti-PEG antibodies

  Presence and levels of anti-PEG antibodies in plasma as measured by antibody titers

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

Secondary Outcomes (12)

• Changes in pegtibatinase levels

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

• Changes in Met cycle metabolites levels - tHcy

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

• Changes in Met cycle metabolites levels - total Cys

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

• Changes in Met cycle metabolites levels - Met

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

• Changes in Met cycle metabolites levels - Cth

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

Study Arms (2)

Pegtibatinase

ACTIVE COMPARATOR

Drug: Pegtibatinase

Placebo

PLACEBO COMPARATOR

Drug: Placebo

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

Placebo DRUG

Normal saline for subcutaneous injection

Placebo

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of homocystinuria based on genetic confirmation and plasma tHcy ≥50 micromoles and documentation of previous tHcy level ≥80 micromoles
• Willing and able to provide written, signed informed consent and to comply with all study related procedures.
• Subjects born biologically as female who are of child-bearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study. Subjects born biologically as male who identify as female and are not of childbearing potential are not required to undergo pregnancy tests
• Sexually active subjects who have childbearing potential or those who have partners of childbearing potential must be willing to use acceptable methods of contraception while on the study and for 4 weeks after the end of study
• Willing to maintain a stable diet with no significant modifications while on study and complete a daily diet diary.

You may not qualify if:

• Previous exposure to pegtibatinase and/or previous participation in a clinical trial that included administration of pegtibatinase
• Use of any investigational product or investigational medical device within 30 days prior to Screening, or while on study
• Use or planned use of any injectable drugs containing PEG (other than pegtibatinase or COVID-19 vaccines), including medroxyprogesterone (eg, Depo-Provera) injection, within 3 months prior to Screening and during study participation
• Known hypersensitivity to PEG-containing product or any components of pegtibatinase
• A positive test for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody
• A history of organ transplantation, chronic immunosuppressive therapy, or substance abuse
• Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) or to breastfeed at any time during the study
• Concurrent disease or condition or planned major surgery that would interfere with study participation or safety in the opinion of the investigator.
• Any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study
• Major surgery planned during the study period

Sponsors & Collaborators

• Travere Therapeutics, Inc.: lead

Study Sites (8)

Travere Investigational Site - Virtual Site

Culver City, California, 90230, United States

Location

Travere Investigational Site

Aurora, Colorado, 80045, United States

Location

Travere Investigational Site

Miami, Florida, 33136, United States

Location

Travere Investigational Site

Indianapolis, Indiana, 46202, United States

Location

Travere Investigational Site

Portland, Maine, 04102, United States

Location

Travere Investigational Site

Boston, Massachusetts, 02115, United States

Location

Travere Investigational Site

New York, New York, 10029, United States

Location

Travere Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

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

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

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: January 23, 2018
• Study Start: January 22, 2019
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 22, 2024

Record last verified: 2024-11

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 (8)