Pegtibatinase for Homocystinuria

Recruiting at 8 trial locations

Overseen By Travere Call Center

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Travere Therapeutics, Inc.

Must not be taking: Injectable PEG drugs

Disqualifiers: HIV, Hepatitis B/C, Organ transplant, others

Compensation: Varies

Number of Visits: Unknown

Duration: 10 months

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use any investigational products or injectable drugs containing PEG (except for pegtibatinase or COVID-19 vaccines) within 3 months before the study and during participation.

Is Pegtibatinase safe for humans?

Research on a similar treatment, PEGylated cystathionine β-synthase, in mice showed it improved liver symptoms and increased survival, suggesting it might be safe. However, specific human safety data for Pegtibatinase is not provided in the available research. ^{1 2 3 4 5}

How is the drug Pegtibatinase different from other treatments for homocystinuria?

Pegtibatinase is unique because it is a PEGylated enzyme replacement therapy designed to act as a metabolic sink, reducing high levels of homocysteine in the body, which is not effectively addressed by current treatments. This approach involves modifying the enzyme to improve its stability and effectiveness, offering a novel way to manage homocystinuria. ^{6 7 8 9 10}

What is the purpose of this trial?

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.

Research Team

Michael Imperiale, MD

Principal Investigator

Travere Therapeutics, Inc.

Eligibility Criteria

This trial is for individuals with confirmed homocystinuria, evidenced by specific blood test levels. Participants must be able to consent and follow study procedures, including maintaining a stable diet and using contraception if they have childbearing potential. Exclusions include recent use of investigational products, exposure to pegtibatinase, pregnancy or breastfeeding, certain health risks as assessed by the investigator, use of PEG-containing injectables (except some vaccines), and positive tests for HIV or hepatitis.

Inclusion Criteria

I can become pregnant and will take pregnancy tests during the study.

Willing and able to provide written, signed informed consent and to comply with all study related procedures

I am willing to use birth control during and 4 weeks after the study.

Exclusion Criteria

I have had an organ transplant, take immunosuppressants, or have a history of substance abuse.

I haven't used any PEG-containing injectable drugs recently, except for pegtibatinase or COVID-19 vaccines.

I haven't used any experimental drugs or devices in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pegtibatinase or placebo subcutaneously to assess safety, tolerability, pharmacokinetics, and pharmacodynamics

10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pegtibatinase

Trial Overview The COMPOSE trial is testing Pegtibatinase as an enzyme therapy against a placebo in patients with Homocystinuria caused by Cystathionine Beta-Synthase Deficiency. The aim is to introduce CBS enzyme into circulation to reduce harmful homocysteine levels and improve related symptoms affecting eyes, central nervous system, skeleton, and vascular system.

Participant Groups

Group I: Pegtibatinase Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Travere Therapeutics, Inc.

Lead Sponsor

Trials

23

Recruited

103,000+

Orphan Technologies Ltd

Lead Sponsor

Trials

2

Recruited

180+

References

1. Canada pubmed.ncbi.nlm.nih.gov

Current and Novel Therapeutical Approaches of Classical Homocystinuria in Childhood With Special Focus on Enzyme Replacement Therapy, Liver-Directed Therapy and Gene Therapy. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Enzyme replacement with PEGylated cystathionine β-synthase ameliorates homocystinuria in murine model. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Screening of homocysteine from newborn blood spots by high-performance liquid chromatography with coulometric array detection. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Diagnosis of Classic Homocystinuria in Two Boys Presenting with Acute Cerebral Venous Thrombosis and Neurologic Dysfunction after Normal Newborn Screening. [2021]

5. France pubmed.ncbi.nlm.nih.gov

[Homocystinuria in adulthood]. [2016]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of PEGylated truncated human cystathionine beta-synthase for treatment of homocystinuria. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Engineering and Characterization of an Enzyme Replacement Therapy for Classical Homocystinuria. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Nutrition status of adults with phenylketonuria treated with pegvaliase. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Case-control study about the acceptance of Pegvaliase in Phenylketonuria. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Pegvaliase for the treatment of phenylketonuria: A pivotal, double-blind randomized discontinuation Phase 3 clinical trial. [2022]