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Pegtibatinase versus placebo for people 12–65 with classical CBS‑deficient homocystinuria on standard care

A Phase 3, Parallel-Group Treatment, Blinded, Randomized, Placebo-Controlled Study To Assess The Efficacy And Safety Of Pegtibatinase Administered Subcutaneously In Addition To Standard Of Care In Participants With Classical Homocystinuria Due To Cystathionine Beta Synthase Deficiency (HARMONY)

Phase 3 Interventional Travere Therapeutics, Inc. · NCT06247085

This trial tests whether pegtibatinase is safe and can lower homocysteine levels in people aged 12–65 with classical homocystinuria who are already receiving standard treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment70 (estimated)
Ages12 Years to 65 Years
SexAll
SponsorTravere Therapeutics, Inc. Industry-sponsored
Locations52 sites (Phoenix, Arizona and 51 other locations)
Trial IDNCT06247085 on ClinicalTrials.gov

What this trial studies

This is a global, randomized, double‑blind, placebo‑controlled Phase 3 trial enrolling about 70 participants with classical CBS‑deficient homocystinuria who have elevated total homocysteine despite standard care. After a screening period that includes a diet standardization phase to stabilize protein intake, participants are randomized 1:1 to pegtibatinase or placebo for a 24‑week blinded treatment period with an initial 2‑week dose titration and a 22‑week assessment window. Study procedures include regular clinic and some home visits for drug administration, dietary monitoring using an HCU‑specific tool (SING), and remote visits as appropriate. Safety follow‑up is performed 4 weeks after the last dose, with an option to enroll in a long‑term extension (ENSEMBLE) if eligible.

Who should consider this trial

Good fit: Ideal candidates are people aged 12–65 with genetically or biochemically confirmed classical CBS‑deficient homocystinuria, on stable standard-of-care treatments and diet, and with elevated total homocysteine (generally ≥80 µM, with limited enrollment allowed down to ≥50 µM).

Not a fit: Patients with non‑CBS causes of hyperhomocysteinemia, very low baseline tHcy (<50 µM), unstable diet or treatment regimens, pregnancy, or other exclusionary medical conditions (e.g., certain connective tissue diagnoses) are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, pegtibatinase could meaningfully lower plasma homocysteine and reduce the risk of complications associated with classical homocystinuria.

How similar studies have performed: Enzyme‑based approaches like pegtibatinase have shown promise in preclinical and early‑phase work, but randomized phase 3 evidence in this population is limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Must be ≥12 to ≤65 years of age, at the time of signing the informed consent
* Must have a diagnosis of classical HCU based on clinical, biochemical, and/or molecular genetic testing
* 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
* Participants who can become pregnant must have a negative pregnancy test before starting the study and must use a highly effective form of birth control (less than 1% risk of pregnancy per year) during the study and for at least 4 weeks after the last dose.
* Willing to maintain a generally stable diet for the duration of the study (unless changes are required based on medical/safety reasons)
* Willing to maintain generally stable intake and doses of betaine, pyridoxine, and medical food for the duration of the study (unless changes are required based on medical/safety reasons)

Exclusion Criteria:

* Diagnosis of Marfan syndrome, methylenetetrahydrofolate reductase (MTHFR) deficiency, or disorder of cobalamin metabolism
* Concurrent disease or condition (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease) that would interfere with study participation or safety (excluding complications of HCU).
* History of major thrombotic event (eg, cerebrovascular accident, myocardial infarction, pulmonary embolism) in the previous 6 months.
* Body weight ≥160 kg.
* Use or planned use of any injectable drugs containing PEG (excluding PEG-containing vaccines)
* Any previous exposure to pegtibatinase and/or previous participation in a clinical study that included administration of pegtibatinase or pegtarviliase
* Prior severe immune reaction to a PEG-containing product

Where this trial is running

Phoenix, Arizona and 51 other locations

+2 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions HomocystinuriaHCUcystathionine beta synthase deficiencyClassical Homocystinuria
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.