Pegtibatinase for Homocystinuria

(HARMONY Trial)

Recruiting at 1 trial location

Overseen By Mehul Shah

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Travere Therapeutics, Inc.

Must be taking: Betaine, Pyridoxine, Met free formula

Must not be taking: Injectable PEG drugs

Disqualifiers: Marfan syndrome, MTHFR deficiency, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to keep their intake and doses of betaine, pyridoxine, and Met free formula stable during the study, unless changes are needed for medical reasons. The protocol does not specify about other medications, so it's best to discuss with the study team.

Is Pegtibatinase safe for humans?

Research on PEGylated cystathionine β-synthase (a form of enzyme replacement therapy similar to Pegtibatinase) in mice showed improved liver symptoms and increased survival, suggesting it may be safe, but human safety data is not provided. ^{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?

The purpose of this study is to measure efficacy and safety of pegtibatinase treatment compared with placebo in participants with classical HCU receiving standard of care who have not achieved tHcy target levels. Study details include: * Total Study duration: up to 38 weeks * Screening: * Initial Screening duration: up to 4 weeks * Pre-treatment Diet Standardization Period duration: up to 6 weeks * Blinded Treatment Duration: 24 weeks * 2-week blinded dose titration period * 22-week blinded assessment period * Safety Follow-Up: 4 weeks after last dose (as applicable for those not enrolling in the long term extension study, ENSEMBLE)

Research Team

Michael Imperiale, MD

Principal Investigator

Travere Therapeutics, Inc.

Eligibility Criteria

This trial is for people aged 12 to 65 with classical Homocystinuria (HCU) due to a specific enzyme deficiency, who are on standard treatments but haven't hit their target homocysteine levels. Participants must be stable on current treatment and able to follow the study's diet requirements.

Inclusion Criteria

I have been diagnosed with classical homocystinuria.

Willing to maintain a generally stable diet for the duration of the study (unless changes are required based on medical/safety reasons)

Plasma tHcy ≥80 µM at Screening visit, with allowance for up to 18 participants who may be enrolled with a Screening plasma tHcy ≥50 to <80 µM

Exclusion Criteria

I have been diagnosed with Marfan syndrome, MTHFR deficiency, or a cobalamin metabolism disorder.

Concurrent disease or condition that would interfere with study participation or safety (excluding complications of HCU)

I have not had a major blood clot in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Pre-treatment Diet Standardization Period

Participants undergo a diet standardization period to minimize variability in protein intake and supplements

6 weeks

Diet monitoring visits

Blinded Treatment

Participants receive either pegtibatinase or placebo with regular monitoring of dietary protein intake and HCU treatment compliance

24 weeks

Regular intervals including home visits and some remote visits

Safety Follow-Up

Participants are monitored for safety after the last dose

4 weeks

Follow-up visits

Treatment Details

Interventions

• Pegtibatinase

Trial Overview The trial tests Pegtibatinase against a placebo in HCU patients. It lasts up to 38 weeks, including screening, diet standardization before treatment, a blinded treatment phase of 24 weeks with dose adjustments and evaluations, followed by safety monitoring.

Participant Groups

Group I: pegtibatinase Experimental Treatment 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+

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

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]