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

Sponsor
Travere Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03406611
Collaborator
(none)
32
Enrollment
7
Locations
2
Arms
76.3
Anticipated Duration (Months)
4.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
32 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official 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)
Actual Study Start Date :
Jan 22, 2019
Anticipated Primary Completion Date :
Oct 1, 2022
Anticipated Study Completion Date :
Jun 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Pegtibatinase

Drug: Pegtibatinase
Pegtibatinase sterile solution for subcutaneous injection
Other Names:
  • TVT-058
  • OT-58
  • PEG modified CBS, PEG htCBS C15S, htCBS C15S ME-200GS

    		•
    Placebo Comparator: Placebo

    Drug: Placebo
    Normal saline for subcutaneous injection

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of AEs [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 [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 [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 Outcome Measures

    1. Changes in pegtibatinase levels [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 [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 [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 [Through double-blind study completion, approximately 10 months per patient]

      Changes in methionine levels in micromoles

    5. Changes in Met cycle metabolites levels - Cth [Through double-blind study completion, approximately 10 months per patient]

      Changes in cystathionine levels in micromoles

    6. Changes in Met cycle metabolites levels - Phe [Through double-blind study completion, approximately 10 months per patient]

      Changes in phenylalanine levels in micromoles

    7. Descriptive ophthalmology examination findings [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 [Through double-blind study completion, approximately 10 months per patient]

    9. Cognitive assessments using the National Institutes of Health Toolbox Cognition Battery score [Through double-blind study completion, approximately 10 months per patient]

    10. Patient Reported Outcome (PRO): Quality of Life in Neurological Disorders [Neuro-QoL] [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] [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] [Through double-blind study completion, approximately 10 months per patient]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Travere Investigational Site Aurora Colorado United States 80045
    2 Travere Investigational Site Miami Florida United States 33136
    3 Travere Investigational Site Indianapolis Indiana United States 46202
    4 Travere Investigational Site Portland Maine United States 04102
    5 Travere Investigational Site Boston Massachusetts United States 02115
    6 Travere Investigational Site New York New York United States 10029
    7 Travere Investigational Site Philadelphia Pennsylvania United States 19104

    Sponsors and Collaborators

    • Travere Therapeutics, Inc.

    Investigators

    • Study Director: Feriandas Greblikas, Travere Therapeutics, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Travere Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT03406611
    Other Study ID Numbers:
    • CBS-HCY-CT-01
    First Posted:
    Jan 23, 2018
    Last Update Posted:
    Jul 13, 2022
    Last Verified:
    Jul 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Homocystinuria

    Study Results

    No Results Posted as of Jul 13, 2022