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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03406611
Other study ID # CBS-HCY-CT-01
Secondary ID
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date January 22, 2019
Est. completion date December 2026

Study information

Verified date January 2024
Source Travere Therapeutics, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 32
Est. completion date December 2026
Est. primary completion date June 2026
Accepts healthy volunteers No
Gender All
Age group 12 Years to 65 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Pegtibatinase
Pegtibatinase sterile solution for subcutaneous injection
Placebo
Normal saline for subcutaneous injection

Locations

Country Name City State
United States Travere Investigational Site Aurora Colorado
United States Travere Investigational Site Boston Massachusetts
United States Travere Investigational Site - Virtual Site Culver City California
United States Travere Investigational Site Indianapolis Indiana
United States Travere Investigational Site Miami Florida
United States Travere Investigational Site New York New York
United States Travere Investigational Site Philadelphia Pennsylvania
United States Travere Investigational Site Portland Maine

Sponsors (1)

Lead Sponsor Collaborator
Travere Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of AEs Incidence of AEs (by type, severity and relationship to study drug) Through double-blind study completion, approximately 10 months per patient
Primary 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
Primary 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 Changes in pegtibatinase levels Changes in pegtibatinase levels following single and repeat administration at specified timepoints Through double-blind study completion, approximately 10 months per patient
Secondary Changes in Met cycle metabolites levels - tHcy Changes in total homocysteine levels in micromoles Through double-blind study completion, approximately 10 months per patient
Secondary Changes in Met cycle metabolites levels - total Cys Changes in total cysteine levels in micromoles Through double-blind study completion, approximately 10 months per patient
Secondary Changes in Met cycle metabolites levels - Met Changes in methionine levels in micromoles Through double-blind study completion, approximately 10 months per patient
Secondary Changes in Met cycle metabolites levels - Cth Changes in cystathionine levels in micromoles Through double-blind study completion, approximately 10 months per patient
Secondary Changes in Met cycle metabolites levels - Phe Changes in phenylalanine levels in micromoles Through double-blind study completion, approximately 10 months per patient
Secondary Descriptive ophthalmology examination findings 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. Through double-blind study completion, approximately 10 months per patient
Secondary Bone densitometry using dual-energy X-ray absorptionmetry (DEXA) scans Through double-blind study completion, approximately 10 months per patient
Secondary Cognitive assessments using the National Institutes of Health Toolbox Cognition Battery score Through double-blind study completion, approximately 10 months per patient
Secondary Patient Reported Outcome (PRO): Quality of Life in Neurological Disorders [Neuro-QoL] 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 Through double-blind study completion, approximately 10 months per patient
Secondary 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
Secondary Patient Reported Outcome (PRO): Quality of Life by EuroQol 5-Dimentional Instrument [EQ 5D] Through double-blind study completion, approximately 10 months per patient
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