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

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ClinicalTrials.gov Identifier: NCT03406611
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : September 5, 2021
Sponsor:
Collaborator:
Travere Therapeutics, Inc.
Information provided by (Responsible Party):
Orphan Technologies Ltd

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 levels and normalized cysteine (Cys) levels.


Condition or disease Intervention/treatment Phase
Homocystinuria Drug: Pegtibatinase Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 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 : January 22, 2019
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : June 2025


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




Primary Outcome Measures :
  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 Outcome Measures :
  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. 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.

  7. Bone densitometry using dual-energy X-ray absorptionmetry (DEXA) scans [ Time Frame: Through double-blind study completion, approximately 10 months per patient ]
  8. Cognitive assessments using the National Institutes of Health Toolbox Cognition Battery score [ Time Frame: Through double-blind study completion, approximately 10 months per patient ]
  9. 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

  10. 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 ]
  11. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Females of child-bearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study
  • Sexually active patients must be willing to use acceptable method 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
  • In generally good health, except for possible complications of homocystinuria

Exclusion Criteria:

  • Previous exposure to pegtibatinase and/or previous participation in pegtibatinase clinical trials
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03406611


Contacts
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Contact: Travere Call Center 1-877-659-5518 medinfo@travere.com

Locations
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United States, Colorado
Travere Investigational Site Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Travere Investigational Site Recruiting
Miami, Florida, United States, 33136
United States, Indiana
Travere Investigational Site Recruiting
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Travere Investigational Site Recruiting
Boston, Massachusetts, United States, 02115
United States, New York
Travere Investigational Site Recruiting
New York, New York, United States, 10029
United States, Pennsylvania
Travere Investigational Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Orphan Technologies Ltd
Travere Therapeutics, Inc.
Investigators
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Study Director: Feriandas Greblikas Travere Therapeutics, Inc.
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Responsible Party: Orphan Technologies Ltd
ClinicalTrials.gov Identifier: NCT03406611    
Other Study ID Numbers: CBS-HCY-CT-01
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: September 5, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Homocystinuria
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
Connective Tissue Diseases
Metabolic Diseases