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NCT Number: NCT03406611

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

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.

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Key information

Conditions

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

Age range

12 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Travere Investigational Site - Virtual Site, Culver City, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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

Treatment and study plan

Pegtibatinase

Drug

Pegtibatinase sterile solution for subcutaneous injection

Other names: TVT-058, OT-58, PEG modified CBS, PEG htCBS C15S, htCBS C15S ME-200GS

Placebo

Drug

Normal saline for subcutaneous injection

Primary outcomes

  1. Incidence of AEs

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

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

  2. Anti-pegtibatinase antibodies

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

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

  3. Anti-PEG antibodies

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

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

Secondary outcomes

  1. Changes in pegtibatinase levels

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

    Changes in pegtibatinase levels following single and repeat administration at specified timepoints

  2. Changes in Met cycle metabolites levels - tHcy

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

    Changes in total homocysteine levels in micromoles

  3. Changes in Met cycle metabolites levels - total Cys

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

    Changes in total cysteine levels in micromoles

  4. Changes in Met cycle metabolites levels - Met

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

    Changes in methionine levels in micromoles

  5. Changes in Met cycle metabolites levels - Cth

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

    Changes in cystathionine levels in micromoles

  6. Changes in Met cycle metabolites levels - Phe

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

    Changes in phenylalanine levels in micromoles

  7. Descriptive ophthalmology examination findings

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

    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.

  8. Bone densitometry using dual-energy X-ray absorptionmetry (DEXA) scans

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

  9. Cognitive assessments using the National Institutes of Health Toolbox Cognition Battery score

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

  10. Patient Reported Outcome (PRO): Quality of Life in Neurological Disorders [Neuro-QoL]

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

    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

  11. Patient Reported Outcome (PRO): Quality of Life by 36-Item Short Form Survey [SF-36]

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

  12. Patient Reported Outcome (PRO): Quality of Life by EuroQol 5-Dimentional Instrument [EQ 5D]

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

Sponsors and collaborators

Lead sponsor

Travere Therapeutics, Inc.

Industry

Registry information

Official study title

A Double Blind, Randomized, Placebo-controlled, Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Effects on Clinical Outcomes of Pegtibatinase (TVT-058), Administered Subcutaneously in Patients with Cystathionine Beta-Synthase Deficient Homocystinuria (COMPOSE)

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
Jan 23, 2018
Registry last updated
Nov 22, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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