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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Bile Acid Synthesis Defect

Intervention / Treatment
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* Drug: Cholic Acid


Participation Criteria
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Eligibility Criteria
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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. The subject and/or parent/legal guardian must have provided informed consent prior to study start. The subject must have a diagnosis of an inborn error of bile acid synthesis. The subject must be willing and able to comply with all study assessments and procedures. Subjects with other organ dysfunction will not be excluded
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cholic Acid<br>Active drug | Drug: Cholic Acid<br>* 10-15 mg/kg body weight/day supplied in 50 or 250 mg Cholic Acid Capsules<br>* Other names: Cholic Acid Capsules;|

What is the study measuring?
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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) | 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 | 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 | 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 | 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) | 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 | 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 | 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 | 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 | 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 | Number (%) of patients with any AE | At baseline, then every 12 months for an average of 3.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholic Acid, Inborn Error, Bile Acid Metabolism, Inborn Error of Bile Acid Synthesis