Pegtibatinase for Homocystinuria

(ENSEMBLE Trial)

Enrolling by invitation at 4 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Travere Therapeutics, Inc.

Disqualifiers: Serious AE, Intolerance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a treatment called pegtibatinase for individuals with classical homocystinuria (HCU), a condition that can lead to vision issues and blood clots. The main goal is to evaluate the treatment's safety and effectiveness over an extended period. Participants currently in the COMPOSE study or those who have completed the HARMONY study might be eligible. The trial will last up to 13 months to collect and assess safety and effectiveness data. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to help bring a potentially effective treatment closer to market.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Previous studies have generally shown that participants tolerate pegtibatinase well. Research indicates it can significantly lower total homocysteine (tHcy) levels, offering promise for treating homocystinuria. Most participants did not experience severe side effects such as anaphylaxis, a serious allergic reaction. About 62.5% of participants experienced some treatment-related side effects, but these were not severe. This suggests pegtibatinase is safe for most people, though monitoring for side effects during treatment remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pegtibatinase is unique because it targets homocystinuria by breaking down excess homocysteine directly, a different approach compared to standard treatments like vitamin B6, vitamin B12, folate, and betaine, which often focus on enzyme cofactors or pathways to reduce homocysteine levels. This enzyme therapy aims to directly reduce homocysteine levels in the blood more effectively. Researchers are excited about pegtibatinase because it offers a novel mechanism of action that could potentially provide better control of homocystinuria symptoms and complications compared to existing options.

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

Research has shown that pegtibatinase, the treatment under study in this trial, is a promising option for classical homocystinuria (HCU). Studies have found that patients generally tolerate it well and that it significantly lowers levels of total homocysteine (tHcy), a harmful substance that accumulates in people with HCU. Specifically, the highest dose of pegtibatinase led to quick and lasting decreases in tHcy levels. These findings suggest that pegtibatinase could effectively manage HCU. ^{1 2 3 5 6}

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) who are currently in the COMPOSE study or have finished the HARMONY study's initial 24 weeks. Participants will be involved for roughly 13 months, including a treatment phase of up to one year and a safety follow-up of four weeks.

Inclusion Criteria

Participants active in the Phase 1/2 COMPOSE study or who completed the 24-week blinded period in the Phase 3 HARMONY study

Exclusion Criteria

I was removed from a previous pegtibatinase study due to a severe side effect or intolerance.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pegtibatinase treatment for long-term safety and efficacy assessment

104 weeks

Self-administration with regular clinical assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Pegtibatinase

Trial Overview The trial is testing Pegtibatinase's long-term effects on patients with HCU. It aims to understand how safe and effective this treatment is over an extended period when given weekly.

How Is the Trial Designed?

Group I: pegtibatinase Experimental Treatment 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. 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.

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06247085

NCT06247085 | A Study to Investigate Efficacy and Safety ... A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) ...

5. gimopen.org gimopen.org/article/S2949-7744(24)00035-9/fulltext

Pegtibatinase, an investigational enzyme replacement ... These results demonstrate the potent treatment effect of pegtibatinase on tHcy reduction and support its further development as a novel therapy for HCU.

6. 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.