Pegtibatinase for Homocystinuria

(HARMONY Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called pegtibatinase, an enzyme therapy, to determine its safety and effectiveness for individuals with classical homocystinuria (HCU), a genetic condition affecting amino acid processing. The goal is to see if pegtibatinase can help those who haven't reached their target levels of tHcy, a substance that can cause health issues if elevated. Participants will receive either the treatment or a placebo (a harmless pill resembling the treatment) and must maintain a stable diet and supplement regimen. This trial may suit those with classical HCU who struggle to control their tHcy levels and can commit to a stable diet during the study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for HCU.

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 there any evidence suggesting that pegtibatinase treatment is likely to be safe for humans?

Research has shown that pegtibatinase is generally safe for humans. In earlier studies, the treatment demonstrated good safety results, with most participants not experiencing serious side effects. Importantly, no severe allergic reactions, such as anaphylaxis, occurred. In one study, 62.5% of participants experienced some side effects related to the treatment, but these were not serious. Pegtibatinase also successfully lowered tHcy levels, indicating potential for treating homocystinuria (HCU), a rare genetic disorder affecting metabolism. Overall, the evidence suggests that pegtibatinase is a promising and well-tolerated option for people with HCU. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pegtibatinase is unique because it offers a new way to manage homocystinuria by breaking down harmful levels of homocysteine in the body. Unlike traditional treatments that primarily focus on dietary restrictions and vitamin supplements like pyridoxine or betaine, pegtibatinase acts as an enzyme replacement, specifically targeting and reducing homocysteine levels. Researchers are excited because this mechanism could provide a more direct and potentially more effective approach to managing the condition, improving patient outcomes and quality of life.

What evidence suggests that pegtibatinase might be an effective treatment for homocystinuria?

Research shows that pegtibatinase, which participants in this trial may receive, may help treat classical homocystinuria (HCU). Studies have found it can significantly reduce total homocysteine (tHcy) levels in the blood, crucial for managing HCU. In earlier studies, patients tolerated the treatment well. The highest dose tested led to rapid and lasting reductions in tHcy levels. This suggests pegtibatinase could benefit those who haven't achieved their tHcy goals with current treatments. ^{1 5 6 7 8}

Who Is on the Research Team?

Michael Imperiale, MD

Principal Investigator

Travere Therapeutics, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1098360025001030

Clinical Trial Safety and efficacy of pegtibatinase enzyme ... Pegtibatinase was generally well tolerated and substantially reduced tHcy levels, demonstrating potential as a treatment for HCU.

2. ir.travere.com ir.travere.com/news-releases/news-release-details/travere-therapeutics-announces-positive-topline-results-cohort-6/

News In this highest dose cohort to date, treatment with pegtibatinase resulted in rapid and sustained reductions in total homocysteine (tHcy), with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06247085

A Study to Investigate Efficacy and Safety of Pegtibatinase ... A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40382700/

Safety and efficacy of pegtibatinase enzyme replacement ... Pegtibatinase was generally well tolerated and substantially reduced tHcy levels, demonstrating potential as a treatment for HCU.

5. ir.travere.com ir.travere.com/news-releases/news-release-details/travere-therapeutics-initiates-pivotal-phase-3-clinical-trial/

Travere Therapeutics Initiates Pivotal Phase 3 Clinical Trial ... The study is designed to determine the safety and efficacy of pegtibatinase in reducing plasma total homocysteine (tHcy) levels, a key treatment goal in ...

6. travere.com travere.com/our-science/our-pipeline/pegtibatinase/

Pegtibatinase - Investigational Therapy for Classical HCU Pegtibatinase is currently advancing in a Phase 1/2 dose escalation study to assess its safety, tolerability, pharmacokinetics, pharmacodynamics and clinical ...

7. ir.travere.com ir.travere.com/press-releases/news-details/2025/Travere-Therapeutics-Presents-Abstracts-at-the-15th-International-Congress-of-Inborn-Errors-of-Metabolism/default.aspx

Travere Therapeutics Presents Abstracts at the 15th ... Presentation details long-term safety and efficacy data on pegtibatinase as a potential treatment for classical HCU.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06247085

NCT06247085 | A Study to Investigate Efficacy and Safety ... The purpose of this study is to measure efficacy and safety of pegtibatinase treatment compared with placebo in participants with classical HCU receiving ...