Clinical trial NCT03406611: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Homocystinuria
Lead sponsor: Travere Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-01-23
Enrollment: 32
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of AEs
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Anti-pegtibatinase antibodies
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Anti-PEG antibodies
timeFrame: Through double-blind study completion, approximately 10 months per patient
Secondary outcomes:
measure: Changes in pegtibatinase levels
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Changes in Met cycle metabolites levels - tHcy
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Changes in Met cycle metabolites levels - total Cys
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Changes in Met cycle metabolites levels - Met
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Changes in Met cycle metabolites levels - Cth
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Changes in Met cycle metabolites levels - Phe
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Descriptive ophthalmology examination findings
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Bone densitometry using dual-energy X-ray absorptionmetry (DEXA) scans
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Cognitive assessments using the National Institutes of Health Toolbox Cognition Battery score
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Patient Reported Outcome (PRO): Quality of Life in Neurological Disorders [Neuro-QoL]
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Patient Reported Outcome (PRO): Quality of Life by 36-Item Short Form Survey [SF-36]
timeFrame: Through double-blind study completion, approximately 10 months per patient
measure: Patient Reported Outcome (PRO): Quality of Life by EuroQol 5-Dimentional Instrument [EQ 5D]
timeFrame: Through double-blind study completion, approximately 10 months per patient
Other outcomes:
Locations:
city: Culver City
country: United States
facility: Travere Investigational Site - Virtual Site
state: California
city: Aurora
country: United States
facility: Travere Investigational Site
state: Colorado
city: Miami
country: United States
facility: Travere Investigational Site
state: Florida
city: Indianapolis
country: United States
facility: Travere Investigational Site
state: Indiana
city: Portland
country: United States
facility: Travere Investigational Site
state: Maine
city: Boston
country: United States
facility: Travere Investigational Site
state: Massachusetts
city: New York
country: United States
facility: Travere Investigational Site
state: New York
city: Philadelphia
country: United States
facility: Travere Investigational Site
state: Pennsylvania
Study officials:
affiliation: Travere Therapeutics, Inc.
name: Michael Imperiale, MD
role: STUDY_DIRECTOR
References: