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

Cholestasis Clinical Trial

Official title:

Investigation in the Pathogenesis of Liver Disease in Patients With Inborn Errors of Bile Acid Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00007020
• Other study ID #: CAC-91-10-10
• Secondary ID: CCHMC-91-10-10NC
• Status: Completed
• Phase: Phase 3
• Start date: January 1992
• Est. completion date: December 2009

Study information

• Verified date: September 2023
• Source: Mirum Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Clinical or biochemical evidence of liver disease, unexplained fat-soluble vitamin malabsorption, or peroxisomal dysfunction that compromises bile acid biosynthesis

Inclusion criteria for enrollment were:

• Infants < age 3 months

• Children presenting for evaluation of cholestasis defined as a conjugated bilirubin > 2mg/dl or increased serum bile acids

• Older subjects of any age with cholestatic liver disease if urine screens suggested that they had inborn errors of bile acid metabolism

• Confirmation of a diagnosis of an inborn error of bile acid synthesis based upon urine analysis by FAB-MS to determine whether specific abnormalities in bile acid synthesis are indicated

• The patient and/or parent/legal guardian must have signed the written informed consent document before study start.

• The patient must be willing and able to comply with all study assessments and procedures.

Related Conditions & MeSH terms

• Adrenoleukodystrophy
• Cholestasis
• Infantile Refsum's Disease
• Peroxisomal Disorders
• Refsum Disease
• Zellweger Syndrome

Intervention

Drug:
• Cholic Acids
10-15 mg/kg body weight/day taken orally.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Mirum Pharmaceuticals, Inc.	Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Bilirubin Measured in Serum	Bilirubin concentration in serum at baseline and on treatment	Baseline and on treatment (every 1, 3, or 6 months, depending on protocol version, for an average of 2.8 years)
Primary	Number of Participants With Excretion of Atypical Bile Acids in Urine by Category	Patients with excretion of atypical bile acids in urine by category, from worst status before treatment (baseline, BL) to best status on treatment (OT)	Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Secondary	Change in Liver Function Tests (LFTs) Measured in Serum	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)	Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Secondary	Liver Histology	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).	At baseline (if no historical data were available) and between 1 and 6 months following treatment start.
Secondary	Height and Weight	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	Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Secondary	Adverse Events	Number of patients with any adverse event	Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years