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

Primary Purpose

Homocystinuria

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pegtibatinase
Placebo
Sponsored by
Travere Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Homocystinuria

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Travere Investigational SiteRecruiting
  • Travere Investigational SiteRecruiting
  • Travere Investigational SiteRecruiting
  • Travere Investigational SiteRecruiting
  • Travere Investigational SiteRecruiting
  • Travere Investigational SiteRecruiting
  • Travere Investigational SiteRecruiting
  • Travere Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Pegtibatinase

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Incidence of AEs
Incidence of AEs (by type, severity and relationship to study drug)
Anti-pegtibatinase antibodies
Presence and levels of anti-pegtibatinase antibodies in plasma as measured by antibody titers
Anti-PEG antibodies
Presence and levels of anti-PEG antibodies in plasma as measured by antibody titers

Secondary Outcome Measures

Changes in pegtibatinase levels
Changes in pegtibatinase levels following single and repeat administration at specified timepoints
Changes in Met cycle metabolites levels - tHcy
Changes in total homocysteine levels in micromoles
Changes in Met cycle metabolites levels - total Cys
Changes in total cysteine levels in micromoles
Changes in Met cycle metabolites levels - Met
Changes in methionine levels in micromoles
Changes in Met cycle metabolites levels - Cth
Changes in cystathionine levels in micromoles
Changes in Met cycle metabolites levels - Phe
Changes in phenylalanine levels in micromoles
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.
Bone densitometry using dual-energy X-ray absorptionmetry (DEXA) scans
Cognitive assessments using the National Institutes of Health Toolbox Cognition Battery score
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
Patient Reported Outcome (PRO): Quality of Life by 36-Item Short Form Survey [SF-36]
Patient Reported Outcome (PRO): Quality of Life by EuroQol 5-Dimentional Instrument [EQ 5D]

Full Information

First Posted
December 5, 2017
Last Updated
November 17, 2022
Sponsor
Travere Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03406611
Brief Title
Pegtibatinase as an Enzyme Therapy for Patients With Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency (COMPOSE)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 22, 2019 (Actual)
Primary Completion Date
February 2023 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Travere Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Homocystinuria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pegtibatinase
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Pegtibatinase
Other Intervention Name(s)
TVT-058, OT-58, PEG modified CBS, PEG htCBS C15S, htCBS C15S ME-200GS
Intervention Description
Pegtibatinase sterile solution for subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal saline for subcutaneous injection
Primary Outcome Measure Information:
Title
Incidence of AEs
Description
Incidence of AEs (by type, severity and relationship to study drug)
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Anti-pegtibatinase antibodies
Description
Presence and levels of anti-pegtibatinase antibodies in plasma as measured by antibody titers
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Anti-PEG antibodies
Description
Presence and levels of anti-PEG antibodies in plasma as measured by antibody titers
Time Frame
Through double-blind study completion, approximately 10 months per patient
Secondary Outcome Measure Information:
Title
Changes in pegtibatinase levels
Description
Changes in pegtibatinase levels following single and repeat administration at specified timepoints
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Changes in Met cycle metabolites levels - tHcy
Description
Changes in total homocysteine levels in micromoles
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Changes in Met cycle metabolites levels - total Cys
Description
Changes in total cysteine levels in micromoles
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Changes in Met cycle metabolites levels - Met
Description
Changes in methionine levels in micromoles
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Changes in Met cycle metabolites levels - Cth
Description
Changes in cystathionine levels in micromoles
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Changes in Met cycle metabolites levels - Phe
Description
Changes in phenylalanine levels in micromoles
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Descriptive ophthalmology examination findings
Description
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.
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Bone densitometry using dual-energy X-ray absorptionmetry (DEXA) scans
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Cognitive assessments using the National Institutes of Health Toolbox Cognition Battery score
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
Patient Reported Outcome (PRO): Quality of Life in Neurological Disorders [Neuro-QoL]
Description
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
Time Frame
Through double-blind study completion, approximately 10 months per patient
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Travere Call Center
Phone
1-877-659-5518
Email
medinfo@travere.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sagar A Vaidya, MD, PhD
Organizational Affiliation
Travere Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Travere Investigational Site
City
Culver City
State/Province
California
ZIP/Postal Code
90230
Country
United States
Individual Site Status
Recruiting
Facility Name
Travere Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Name
Travere Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Name
Travere Investigational Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Name
Travere Investigational Site
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Individual Site Status
Recruiting
Facility Name
Travere Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Name
Travere Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Name
Travere Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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