Study to Evaluate Patients With Cerebrotendinous Xanthomatosis (RESTORE)

Study Overview
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Brief Summary
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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)

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

Conditions
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CTX

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 1 Month

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult Cohort<br>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<br>* Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment.<br>Drug: Placebo<br>* Adult cohort patients will receive blinded 250 mg CDCA TID or placebo during the double-blind periods based upon their treatment assignment.<br>Drug: Open-Label CDCA 250 mg TID<br>* 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.<br>Drug: Rescue Medication CDCA 250 mg TID<br>* CDCA 250 mg TID will be provided as rescue medication during the double-blind periods, if needed, based on laboratory results.<br>|
| Experimental: Pediatric Cohort<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bile Alcohols. | Change from baseline in bile alcohols at the end of each DB treatment period. | Week 4 and Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukodystrophy, Cerebrotendinous xanthomatosis, Cholestanol, CYP27A1, CTX