Study to Evaluate Patients With Cerebrotendinous Xanthomatosis (RESTORE)

A Phase 3 Study to Evaluate the Effects of Chenodeoxycholic Acid in Adult and Pediatric Patients With Cerebrotendinous Xanthomatosis

The study is made up of two cohorts: a randomized double-blind crossover (placebo withdrawal with rescue) study among patients ≥ 16 years of age (adult cohort) and an open-label dose titration study among pediatric patients ≥1 month and <16 years of age (pediatric cohort)

Study Overview

• Status: Completed
• Conditions: CTX
• Intervention / Treatment: Drug: Blinded CDCA 250 mg TID; Drug: Placebo; Drug: Open-Label CDCA 250 mg TID; Drug: Rescue Medication CDCA 250 mg TID; Drug: CDCA Weight-Based Dose TID

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60430-270
      • Travere Investigational Site
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Travere Investigational Site
  • SP
    • São Paulo, SP, Brazil, 04024-002
      • Travere Investigational Site
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Travere Investigational Site
  • Florida
    • Orlando, Florida, United States, 32806
      • Travere Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Travere Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Travere Investigational Site
    • New Orleans, Louisiana, United States, 70112
      • Travere Investigational Site
  • New York
    • Great Neck, New York, United States, 11021
      • Travere Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43221
      • Travere Investigational Site
  • Texas
    • Austin, Texas, United States, 78723
      • Travere Investigational Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Travere Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female at least 1 month or older at screening.
2. Clinical diagnosis of CTX with biochemical confirmation.
3. Women of childbearing potential must agree to the use of one highly reliable method of contraception during the study, plus one additional barrier method during sexual activity.
4. Males must be surgically sterile, or males and their sexual partners must together agree to use medically accepted methods of contraception that are considered highly reliable during the course of the study.

Exclusion Criteria:

1. Genetic testing does not confirm CTX.
2. Malabsorption disorder or confounding inflammatory gastrointestinal condition (for example, irritable bowel syndrome).
3. Documented history of heart failure.
4. Treated with medications which impact bile acid absorption such as bile acid sequestering agents (eg, cholestyramine, colestipol, aluminum-based antacids.
5. Treated with cholic acid medication.
6. Female patient who is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
7. Positive at screening for the human immunodeficiency virus (HIV) or markers indicating acute or chronic hepatitis B infection or hepatitis C infection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adult Cohort; Patients in the adult cohort will participate in a randomized, double-blind, placebo-controlled, 2 period × 2-treatment crossover study with rescue medication and open-label run-in to assess the efficacy and safety of CDCA.	Drug: Blinded CDCA 250 mg TID; Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment.; Drug: Placebo; Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment.; Drug: Open-Label CDCA 250 mg TID; Adult cohort patients will receive open-label 250 mg CDCA TID during the run-in and washout periods of the study or as rescue medication during the double-blind periods, if needed, based on clinical symptoms.; Drug: Rescue Medication CDCA 250 mg TID; CDCA 250 mg TID will be provided as rescue medication during the double-blind periods, if needed, based on laboratory results.
Experimental: Pediatric Cohort; Pediatric cohort patients (≥1 month and <16 years) will participate in a 24-week, open-label cohort with an 8-week titration period and a 16-week treatment period at the tolerated dose.	Drug: CDCA Weight-Based Dose TID; Patients in the pediatric cohort will complete a weight-based dose titration to a tolerated dose and will maintain that tolerated dose for the remainder of the study. Pediatric cohort dosing of CDCA will not exceed an equivalent dose of 750 mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Urine 23S-Pentol During the Two Double-Blind Periods	Primary Analysis of Change from Baseline in Urine 23S-Pentol (Natural Log-Transformed) during the Two Double-blind Periods- Paired T-test	Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline Plasma Cholestanol During the Two Double-Blind Periods	Primary Analysis of Change from Baseline Plasma Cholestanol (Natural Log-transformed) at the End of the Two Double-Blind Periods- Paired T-test	Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16
Change From Baseline Plasma 7αC4 During the Two Double-Blind Periods	Primary Analysis of Change from Baseline Plasma 7αC4 (Natural Log-Transformed) During the Two Double-Blind Periods	Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16
Proportion of Participants Who Received Rescue Treatment During Two Double-Blind Periods	Proportion of Participants Who Received Rescue Treatment during Two Double-Blind Periods - Prescott's Method	Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16

Collaborators and Investigators

• Sponsor: Mirum Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2020
• Primary Completion (Actual): July 13, 2023
• Study Completion (Actual): October 4, 2023

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Leukodystrophy; CTX; Cerebrotendinous xanthomatosis; Cholestanol; CYP27A1
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Xanthomatosis, Cerebrotendinous; Xanthomatosis; Gastrointestinal Agents; Cathartics; Chenodeoxycholic Acid
• Other Study ID Numbers: Cheno-CTX-301

Drug and device information, study documents

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