Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid

Phase 3

Completed

Conditions: Zellweger Syndrome
Cholestasis
Infantile Refsum's Disease
Adrenoleukodystrophy
Peroxisomal Disorders

Interventions: Drug: Cholic Acids

Registration Number: NCT00007020

Lead Sponsor: Mirum Pharmaceuticals, Inc.

Brief Summary: OBJECTIVES:

I. To Evaluate the therapeutic efficacy of cholic acid during provision of compassionate treatment to patients with identified inborn errors of bile acid synthesis and metabolism

II. To assess the safety and tolerability of cholic acid

Detailed Description: Investigational Plan:

A Phase III, open label, single arm, nonrandomized, non-comparative, compassionate treatment study of cholic acid in the treatment of defects of bile acid metabolism.

The study was begun with a single study site at Cincinnati Children's Hospital Medical Center (CCHMC), but in 2005 was expanded so that compassionate treatment could be provided to additional patients who had been identified with inborn errors of bile metabolism through the center's screening/diagnostic program.

Patients who were screened were contacted and evaluated with respect to the inclusion/exclusion criteria. Signed informed consent by the patient and/or parents/legal guardian was obtained as soon as it is confirmed that the patient met inclusion/exclusion criteria and the parents/guardian would agree for the child to participate in the study.

The primary interventions for the study were:

1. Administration of study drug.

2. Collection of baseline physical exam, vital signs, blood and urine samples for laboratory tests.

3. Collection of periodic physical exam, vital signs, blood and urine samples for laboratory tests during the period of administration of the study drug.

4. Collection of any adverse event information.

Time and Events Schedule:

Baseline:

1. Confirm eligibility

2. Obtain written informed consent from patient and/or parents/legal guardian

3. Collect demographic data and disease and medication history, including family history

Baseline and Ongoing:

4. Obtain body weight

5. Record adverse events

6. Obtain blood and urine samples for laboratory tests

7. Initiate study drug therapy \& monitor study drug therapy and adjust dose as needed

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 85

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cholic Acid	Cholic Acids	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Excretion of Atypical Bile Acids in Urine by Category	Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years	Patients with excretion of atypical bile acids in urine by category, from worst status before treatment (baseline, BL) to best status on treatment (OT)

Secondary Outcome Measures

Name	Time	Method
Adverse Events	Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years	Number of patients with any adverse event
Liver Histology	At baseline (if no historical data were available) and between 1 and 6 months following treatment start.	Patients (number, percentage) with pathological findings for qualitative (the presence of inflammation, fibrosis, necrosis, giant cells and cholestasis) and quantitative (the degrees of the aforementioned histologic features) liver histopathology at baseline (BL) and on treatment (OT).
Change in Liver Function Tests (LFTs) Measured in Serum	Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years	Patients with elevations of liver function tests (alanine transaminase \[ALT\], aspartate transaminase \[AST\]) measured as multiples of the upper limit of normal (ULN) at baseline (worst value) and on treatment (best value)
Height and Weight	Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years	Change in height/weight percentiles from baseline (worst value) to the best on-treatment value, based on CDC (Centres for Disease Control and Prevention, US) growth chart percentiles