## Protocol Section
### Identification Module
**NCT ID:** NCT06431893

**Acronym:** ENSEMBLE

**Brief Title:** A Phase 3 Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU)

**Official Title:** An Open-Label, Phase 3 Long-Term Extension (LTE) Study To Assess The Safety, Tolerability, And Efficacy Of Treatment With Pegtibatinase In Participants With Classical Homocystinuria (HCU) Due To Cystathionine Beta Synthase Deficiency (ENSEMBLE)

#### Organization Study ID Info
**ID:** TVTX-TVT058-302
#### Organization
**Class:** INDUSTRY
**Full Name:** Travere Therapeutics, Inc.
### Status Module
#### Completion Date
**Date:** 2027-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** ENROLLING_BY_INVITATION

#### Primary Completion Date
**Date:** 2027-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-04-30

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-08
**Study First Submit QC Date:** 2024-05-21
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Travere Therapeutics, Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The goal of this long-term extension (LTE) study is to evaluate the safety and efficacy of pegtibatinase in patients with classical homocystinuria (HCU). Patients who are active in the Phase 1/2 COMPOSE study or those who complete the 24 weeks of treatment in the Phase 3 HARMONY are eligible to participate.

Participants will be in this clinical study for up to about 13 months including:

* a treatment period of up to 52 weeks
* a 4-week safety follow-up period

**Detailed Description:** Overall Design:

This is a global, multicenter, single-arm, open-label study. Participants who meet all eligibility criteria may transition from other pegtibatinase studies and enroll into this LTE study for long-term safety, efficacy, and clinical assessments of pegtibatinase treatment.

All participants will follow a protocol of self-administration of pegtibatinase unless exempted. During the ENSEMBLE study, an optional protein tolerance modification (PTM) sub-study will also be conducted for eligible participants.

### Conditions Module

**Conditions:**

- Homocystinuria

**Keywords:**

- Classical homocystinuria

- HCU

- Cystathionine Beta Synthase Deficiency

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 90

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Pegtibatinase

**Label:** pegtibatinase

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- pegtibatinase

**Description:** Full Target Dose of pegtibatinase BIW

**Name:** Pegtibatinase

**Other Names:**

- OT-58

- TVT-058

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Incidence of treatment-emergent AEs

**Measure:** Treatment-emergent AEs

**Time Frame:** Week 1 - Week 56

**Description:** Incidence of hypermethioninemia

**Measure:** Hypermethioninemia

**Time Frame:** Week 1 - Week 56

**Description:** Incidence of hypomethioninemia

**Measure:** Hypomethioninemia

**Time Frame:** Week 1 - Week 56

**Description:** Incidence of dietary protein rescue

**Measure:** Dietary Protein Rescue

**Time Frame:** Week 1 - Week 56

#### Secondary Outcomes

**Description:** Relative and absolute changes from baseline in tHcy levels

**Measure:** Total Homocysteine (tHcy) Levels

**Time Frame:** Week 1 - Week 56

### Eligibility Module

**Eligibility Criteria:** 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:

* Participant permanently discontinued from study intervention treatment in a previous pegtibatinase study due to serious AE (SAE) or intolerance

**Maximum Age:** 65 Years

**Minimum Age:** 12 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Culver City

**Country:** United States

**Facility:** Travere Investigational Site - Virtual Site

**State:** California

**Zip:** 90230

#### Overall Officials

**Official 1:**

**Affiliation:** Travere Therapeutics, Inc.

**Name:** Sagar A Vaidya, MD, PhD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020739

- Term: Brain Diseases, Metabolic, Inborn

- ID: D000001928

- Term: Brain Diseases, Metabolic

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000020138

- Term: Hyperhomocysteinemia

- ID: D000000592

- Term: Amino Acid Metabolism, Inborn Errors

- ID: D000008661

- Term: Metabolism, Inborn Errors

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000003240

- Term: Connective Tissue Diseases

- ID: D000008659

- Term: Metabolic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M9774

- Name: Homocystinuria

- Relevance: HIGH

- As Found: Homocystinuria

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5205

- Name: Brain Diseases, Metabolic

- Relevance: LOW

- As Found: Unknown

- ID: M22498

- Name: Brain Diseases, Metabolic, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21974

- Name: Hyperhomocysteinemia

- Relevance: LOW

- As Found: Unknown

- ID: M11641

- Name: Metabolism, Inborn Errors

- Relevance: LOW

- As Found: Unknown

- ID: M3932

- Name: Amino Acid Metabolism, Inborn Errors

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M6464

- Name: Connective Tissue Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T2827

- Name: Homocystinuria

- Relevance: HIGH

- As Found: Homocystinuria

- ID: T2828

- Name: Homocystinuria Due to CBS Deficiency

- Relevance: LOW

- As Found: Unknown

- ID: T3036

- Name: Inborn Amino Acid Metabolism Disorder

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006712

- Term: Homocystinuria

### Misc Info Module

- Version Holder: 2024-05-31
