Open Label, Continuation Study of Cholic Acid in Subjects With Inborn Errors of Bile Acid Synthesis

September 29, 2023 updated by: Mirum Pharmaceuticals, Inc.

An Open Label, Single Center, Nonrandomized Continuation Study of Cholic Acid Capsules to Treat Subjects With Inborn Errors of Bile Acid Synthesis

The primary purpose of the study is to evaluate the therapeutic efficacy and safety of cholic acid in subjects with identified inborn errors of bile acid synthesis.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

This is a Phase 3, open-label, single center, nonrandomized study. This continuation protocol will consist of eligible subjects who have previously received cholic acid through the Cincinnati Children's Hospital Medical Center (CCHMC) Compassionate Use (91-10-10), CAC-001-01 study protocols and newly diagnosed subjects.

New subjects will be infants, children, adolescents identified from urine samples obtained from the clinical services of programs across the U.S., Canada, South America, Europe, and Asia. Subject or their legal representative will receive information regarding the study, and the principle investigator (PI) or designee will obtain informed consent. Serum and urine samples will be collected and sent to CCHMC to measure complete bile acid profile analysis. Clinical records including medical history, physical exams, vital signs, and laboratory assessments performed as standard of care will be reviewed to ensure subject eligibility and determine baseline values.

Subjects who have participated in Protocols conducted under IND 45,470 will be consented to continue to receive cholic acid capsules under this continuation protocol. Subjects will serve as their own controls and no placebo will be utilized.

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Subjects who received cholic acid through CCHMC protocols 91-10-10 or CAC-002-01 and meet the following criteria are eligible for study participation.

  1. The subject and/or parent/legal guardian must have provided informed consent prior to study start.
  2. The subject must have a diagnosis of an inborn error of bile acid synthesis.
  3. The subject must be willing and able to comply with all study assessments and procedures.
  4. Subjects with other organ dysfunction will not be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Cholic Acid
Active drug
10-15 mg/kg body weight/day supplied in 50 or 250 mg Cholic Acid Capsules
Other Names:
  • Cholic
  • Cholic Acid Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Atypical Urinary Bile Acid Excretion by FAB-MS (Fast-Atom-Bombardment Ionization-Mass Spectrometry)
Time Frame: At baseline, then every 12 months for an average of 3.5 years
The level of atypical urinary bile acid secretion was scored using a scale of: 0, normal; 1, slight; 2, significant; or 3, marked. A Cochran-Mantel-Haenszel (CMH) test with modified ridit scoring was used to compare the difference between the score at baseline and the worst post-baseline score during treatment with cholic acid in this single-arm trial.
At baseline, then every 12 months for an average of 3.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of Serum Transaminases: ALT
Time Frame: At baseline, then every 12 months for an average of 3.5 years
Changes in ALT were evaluated in terms of elevations above the upper limit of normal (ULN) and were categorized as: <ULN; ≥1 ULN but <2 ULN; ≥2 ULN but <3 ULN; and ≥3x ULN. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented.
At baseline, then every 12 months for an average of 3.5 years
Evaluation of Serum Transaminases: AST
Time Frame: At baseline, then every 12 months for an average of 3.5 years
Changes in AST were evaluated in terms of elevations above the upper limit of normal (ULN) and were categorized as: <ULN; ≥1 ULN but <2 ULN; ≥2 ULN but <3 ULN; and ≥3x ULN. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented.
At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Bilirubin
Time Frame: At baseline, then every 12 months for an average of 3.5 years
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for bilirubin. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Gamma Glutamyl Transferase (GGT)
Time Frame: At baseline, then every 12 months for an average of 3.5 years
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for GGT. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Alkaline Phosphatase
Time Frame: At baseline, then every 12 months for an average of 3.5 years
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for alkaline phosphatase. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Prothrombin Time
Time Frame: At baseline, then every 12 months for an average of 3.5 years
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for prothrombin time. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
At baseline, then every 12 months for an average of 3.5 years
Physical Examinations: Height
Time Frame: At baseline, then every 12 months for an average of 3.5 years
Changes in height percentiles from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial.
At baseline, then every 12 months for an average of 3.5 years
Physical Examinations: Body Weight
Time Frame: At baseline, then every 12 months for an average of 3.5 years
Changes in body weight percentiles from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial.
At baseline, then every 12 months for an average of 3.5 years
Incidence of Adverse Events
Time Frame: At baseline, then every 12 months for an average of 3.5 years
Number (%) of patients with any AE
At baseline, then every 12 months for an average of 3.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Kenneth Setchell, PhD, Children's Hospital Medical Center, Cincinnati
  • Principal Investigator: James E Heubi, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

September 20, 2011

First Submitted That Met QC Criteria

September 21, 2011

First Posted (Estimated)

September 22, 2011

Study Record Updates

Last Update Posted (Actual)

October 3, 2023

Last Update Submitted That Met QC Criteria

September 29, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAC-002-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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