A Study of Chenodeoxycholic Acid (CDCA) in Newly Diagnosed Participants With Cerebrotendinous Xanthomatosis (CTX)

A Phase 3, Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Chenodeoxycholic Acid (CDCA), With an Open-Label Cohort, in Newly Diagnosed Participants With Cerebrotendinous Xanthomatosis (CTX)

This study is designed to demonstrate the beneficial effect of CDCA in the treatment of CTX-associated diarrhea in approximately 10 participants aged 2-75 years old with newly diagnosed CTX or suspected CTX who have never received treatment with CDCA.

Study Overview

• Status: Withdrawn
• Conditions: Cerebrotendinous Xanthomatoses
• Intervention / Treatment: Drug: Chenodeoxycholic acid; Drug: Chenodeoxycholic acid Placebo

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Tel HaShomer, Israel
    • Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent form (or assent form as appliable)
• Aged from 2 to 75 years old
• Has a new or suspected diagnosis of CTX as defined by an elevated plasma cholestanol concentration (>10 mg/L/>25.7 μmol/L) in conjunction with a clinical presentation consistent with the diseased as assessed by the investigator
• Has never received treatment with CDCA
• Has never received treatment with other bile acid products

Exclusion Criteria:

• Any medical condition that, in the opinion of the investigator, precludes the participant's participation in the study
• Presence of known hepatocyte dysfunction or bile ductal abnormalities such as intrahepatic cholestasis, primary biliary cirrhosis or sclerosing cholangitis
• Inability to adhere to treatment and visit schedule
• Female participants who are pregnant
• Female participants who are breast feeding
• Female participants who are using estrogen-containing compounds and cannot/will not discontinue them for the duration of the study
• Female participants of childbearing potential who are not using locally approved birth control method(s) or double barrier contraception (ie, condom and diaphragm, condom or diaphragm and spermicidal gel or foam)
• Taking any of the following medications: bile acid products; inhibitors of bile acid transporters; bile acid binding resins; aluminum-based antacids; coumarin and its derivatives; cholestyramine; ciclosporin; sirolimus; or phenobarbital

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 Diarrhea-Evaluable; Diarrhea-evaluable participants aged 12-75 years old who did not use continence aids that precluded assessment or evaluation of stool frequency and consistency during the screening/baseline period; randomized 1:1 to receive either placebo or CDCA.	Drug: Chenodeoxycholic acid; 250mg capsules; Other Names: CDCA; Drug: Chenodeoxycholic acid Placebo; Placebo to match
Active Comparator: Group 2a Non-Diarrhea Evaluable; Non-diarrhea-evaluable participants aged 12-75 years old who do not have stable, clinically burdensome diarrhea or their diarrhea cannot be fully characterized.	Drug: Chenodeoxycholic acid; 250mg capsules; Other Names: CDCA
Active Comparator: Group 2b Pediatrics; Participants aged 2 to less than 12 years old with or without clinically burdensome diarrhea.	Drug: Chenodeoxycholic acid; 250mg capsules; Other Names: CDCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline at Week 4 in average number of stools with a BSS score of 6 or 7 per day	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma cholestanol levels from baseline to Week 12	All groups combined	Up to 12 weeks
Change in urine and/or plasma bile alcohol levels from baseline to Week 12	All groups combined	Up to 12 weeks
Incidence of, severity/intensity of, and relationship to study drug of AEs		Up to 20 weeks
Incidence of, severity/intensity of, and relationship to study drug of SAEs		Up to 20 weeks
Incidence of, severity/intensity of AESIs	Diarrhea and hepatic dysfunction	Up to 20 weeks
Incidence of, severity/intensity of, and changes in laboratory values		Up to 20 weeks
Incidence of, severity/intensity of, and changes in physical examination		Up to 20 weeks
Incidence of, severity/intensity of, and changes in vital signs		Up to 20 weeks
Number of participants with discontinuations due to AEs		Up to 20 weeks

Collaborators and Investigators

• Sponsor: Leadiant Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2024
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 12, 2024
• First Posted (Actual): February 15, 2024

Study Record Updates

• Last Update Posted (Estimated): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• 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: LBI-CDCA-001; 2023-505759-29-00 (Other Identifier: EU Clinical Trials Register)

Drug and device information, study documents

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