A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care Treatment (HARMONY)

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)

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)

Study Overview

• Status: Recruiting
• Conditions: Homocystinuria
• Intervention / Treatment: Drug: Pegtibatinase; Other: Placebo

Detailed Description

Overall Design:

This global Phase 3 multi-center, multi-national, randomized, blinded, placebo-controlled study will be conducted in participants with classical CBS deficient HCU receiving standard of care who continue to have tHcy levels ≥50 μM. The total study duration will be up to 38 weeks. Approximately 70 participants (35 per arm) will be randomized to receive active drug or placebo (1:1 allocation).

Screening:

Participants will enter into a 2-phase Screening period of up to 10 weeks:

1. Initial Screening: up to 4-week period during which participants will be assessed for eligibility
2. Pre-treatment Diet Standardization Period (DSP): After meeting initial eligibility criteria, participants will begin a pre treatment DSP of up to 6 weeks. The DSP is intended to help minimize variability in protein intake and supplements throughout the randomized portion of the study.

The baseline diet and compliance with HCU-related treatments will be recorded by the dietitian using the HCU-specific diet monitoring tool, called SING (Simplified Ingested Nutrients Guide). The baseline diet and treatment compliance will be used as a reference for future evaluation of daily intact protein intake (DIPI) and HCU treatments.

Blinded Treatment Period:

During the 24-week blinded treatment period, study visits will occur at regular intervals including home visits for study drug administration. Some study visits may be conducted remotely. Dietary protein intake and compliance with HCU treatments will continue to be monitored and recorded to ensure a stable diet and HCU treatment compliance.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Travere Call Center; Phone Number: 1-877-659-5518; Email: medinfo@travere.com

Study Locations

• United States
  • California
    • Culver City, California, United States, 90230
      • Recruiting
      • Travere Investigational Site - Virtual Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• 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 Met free formula 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Other: Placebo; volume-matched saline SC BIW
Experimental: pegtibatinase	Drug: Pegtibatinase; Full Target Dose of pegtibatinase BIW; Other Names: TVT-058; OT-058

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in plasma tHcy levels	The change from baseline in plasma tHcy levels averaged over Weeks 6 through 12 in participants receiving standard of care and treated with pegtibatinase as compared to participants receiving standard of care and placebo	Weeks 6 - 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma tHcy levels	The change from baseline in plasma tHcy levels averaged post Week 12 (Weeks 16, 20, 24)	Weeks 16 - 24

Collaborators and Investigators

• Sponsor: Travere Therapeutics, Inc.
• Investigators: Study Director: Sergio Slawka, MD,MPH,GFMD, Travere Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Estimated): February 7, 2024

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: HCU; cystathionine beta synthase deficiency; Classical Homocystinuria
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Hyperhomocysteinemia; Homocystinuria
• Other Study ID Numbers: TVTX-TVT058-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No