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

Phase 3

Completed

Conditions: Bile Acid Synthesis Defect

Interventions: Drug: Cholic Acid

Registration Number: NCT01438411

Lead Sponsor: Mirum Pharmaceuticals, Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 53

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cholic Acid	Cholic Acid	Active drug

Primary Outcome Measures

Name	Time	Method
Change in Atypical Urinary Bile Acid Excretion by FAB-MS (Fast-Atom-Bombardment Ionization-Mass Spectrometry)	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.

Secondary Outcome Measures

Name	Time	Method
Clinical Laboratory Results: Alkaline Phosphatase	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.
Clinical Laboratory Results: Prothrombin Time	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.
Evaluation of Serum Transaminases: AST	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.
Physical Examinations: Body Weight	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.
Incidence of Adverse Events	At baseline, then every 12 months for an average of 3.5 years	Number (%) of patients with any AE
Evaluation of Serum Transaminases: ALT	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.
Clinical Laboratory Results: Bilirubin	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.
Clinical Laboratory Results: Gamma Glutamyl Transferase (GGT)	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.
Physical Examinations: Height	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.