Study to Evaluate Patients With Cerebrotendinous Xanthomatosis (RESTORE)

NCT04270682 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: Cheno-CTX-301
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 12

Brief Summary

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)

Conditions

CTX

Keywords

Cerebrotendinous xanthomatosis; CTX; Cholestanol; Leukodystrophy; CYP27A1

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change From Baseline Plasma Cholestanol During the Two Double-Blind Periods

  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

  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

  Two double-blind periods: Week 0 to Week 4, Week 12 to Week 16

Study Arms (2)

Adult Cohort

EXPERIMENTAL

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; Drug: Placebo; Drug: Open-Label CDCA 250 mg TID; Drug: Rescue Medication CDCA 250 mg TID

Pediatric Cohort

EXPERIMENTAL

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

Interventions

Blinded CDCA 250 mg TID DRUG

Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment.

Adult Cohort

Placebo DRUG

Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment.

Adult Cohort

Open-Label CDCA 250 mg TID DRUG

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.

Adult Cohort

Rescue Medication CDCA 250 mg TID DRUG

CDCA 250 mg TID will be provided as rescue medication during the double-blind periods, if needed, based on laboratory results.

Adult Cohort

CDCA Weight-Based Dose TID DRUG

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.

Pediatric Cohort

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female at least 1 month or older at screening.
• Clinical diagnosis of CTX with biochemical confirmation.
• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (12)

Travere Investigational Site

Aurora, Colorado, 80045, United States

Location

Travere Investigational Site

Orlando, Florida, 32806, United States

Location

Travere Investigational Site

Iowa City, Iowa, 52242, United States

Location

Travere Investigational Site

New Orleans, Louisiana, 70112, United States

Location

Travere Investigational Site

New Orleans, Louisiana, 70121, United States

Location

Travere Investigational Site

Great Neck, New York, 11021, United States

Location

Travere Investigational Site

Columbus, Ohio, 43221, United States

Location

Travere Investigational Site

Austin, Texas, 78723, United States

Location

Travere Investigational Site

Seattle, Washington, 98195, United States

Location

Travere Investigational Site

Fortaleza, Ceará, 60430-270, Brazil

Location

Travere Investigational Site

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Travere Investigational Site

São Paulo, São Paulo, 04024-002, Brazil

Location

MeSH Terms

Conditions

Xanthomatosis, Cerebrotendinous

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Xanthomatosis

Results Point of Contact

• Title: Mirum Clinical Trials
• Organization: Mirum Pharmaceuticals

medinfo@mirumpharma.com

650-667-4085

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two-cohort study. One cohort is for adult patients with a double-blind placebo withdrawal (with CDCA rescue) crossover. Second cohort will dose titrate pediatric patients into a stable, open-label treatment.

Study Record Dates

• First Submitted: February 12, 2020
• First Posted: February 17, 2020
• Study Start: January 31, 2020
• Primary Completion: July 13, 2023
• Study Completion: October 4, 2023
• Last Updated: October 28, 2024
• Results First Posted: October 28, 2024

Record last verified: 2024-10

Locations

BR (3); US (9)