Study to Evaluate Patients With Cerebrotendinous Xanthomatosis (RESTORE)

• ClinicalTrials.gov Identifier: NCT04270682
• Recruitment Status: Completed
• First Posted: February 17, 2020
• Last Update Posted: November 22, 2023
• Sponsor: Mirum Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Mirum Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: February 12, 2020
• First Posted Date: February 17, 2020
• Last Update Posted Date: November 22, 2023
• Actual Study Start Date: January 31, 2020
• Actual Primary Completion Date: July 13, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 21, 2022)

Change in Bile Alcohols. [ Time Frame: Week 4 and Week 16 ]

Change from baseline in bile alcohols at the end of each DB treatment period.

Original Primary Outcome Measures (submitted: February 12, 2020)

Change in Urinary Bile Alcohols [ Time Frame: Week 4 and Week 16 ]

Change from baseline in urine bile alcohols at the end of each DB treatment period.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate Patients With Cerebrotendinous Xanthomatosis (RESTORE)
• Official Title: A Phase 3 Study to Evaluate the Effects of Chenodeoxycholic Acid in Adult and Pediatric Patients With Cerebrotendinous Xanthomatosis
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: CTX

Intervention

• 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.
• 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.

Study Arms

• 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.
  Interventions:

  • Drug: Blinded CDCA 250 mg TID
  • Drug: Placebo
  • Drug: Open-Label CDCA 250 mg TID
  • Drug: Rescue Medication CDCA 250 mg TID
• 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.
  Intervention: Drug: CDCA Weight-Based Dose TID

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 25, 2023): 18
• Original Estimated Enrollment (submitted: February 12, 2020): 12
• Actual Study Completion Date: October 4, 2023
• Actual Primary Completion Date: July 13, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, United States

Administrative Information

• NCT Number: NCT04270682
• Other Study ID Numbers: Cheno-CTX-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mirum Pharmaceuticals, Inc.
• Original Responsible Party: Travere Therapeutics, Inc.
• Current Study Sponsor: Mirum Pharmaceuticals, Inc.
• Original Study Sponsor: Travere Therapeutics, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Mirum Pharmaceuticals, Inc.
• Verification Date: November 2023