Study to Evaluate Patients With Cerebrotendinous Xanthomatosis (RESTORE)

Phase 3

Completed

• Conditions: CTX
• Interventions: Drug: CDCA Weight-Based Dose TID; Drug: Blinded CDCA 250 mg TID; Drug: Placebo; Drug: Open-Label CDCA 250 mg TID; Drug: Rescue Medication CDCA 250 mg TID

• Registration Number: NCT04270682
• Lead Sponsor: Mirum Pharmaceuticals, Inc.

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)

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-31
• Study First Submitted: 2020-02-12
• Study First Submitted QC: 2020-02-12
• Study First Posted: 2020-02-17
• Primary Completion: 2023-07-13
• Study Completion: 2023-10-04
• Results First Submitted: 2024-07-12
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-24
• Last Update Submitted: 2024-10-24
• Results First Posted: 2024-10-28
• Last Update Posted: 2024-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Pediatric Cohort	CDCA Weight-Based Dose TID	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.
Adult Cohort	Blinded CDCA 250 mg TID	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.
Adult Cohort	Placebo	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.
Adult Cohort	Open-Label CDCA 250 mg TID	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.
Adult Cohort	Rescue Medication CDCA 250 mg TID	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	Primary Analysis of Change from Baseline Plasma Cholestanol (Natural Log-transformed) at the End of the Two Double-Blind Periods- Paired T-test
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	Primary Analysis of Change from Baseline Plasma 7αC4 (Natural Log-Transformed) During the Two Double-Blind Periods
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	Proportion of Participants Who Received Rescue Treatment during Two Double-Blind Periods - Prescott's Method

Trial Locations

Locations (1)

Travere Investigational Site; 🇧🇷 São Paulo, SP, Brazil