Clinical trial NCT00007020: Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
Official title: Investigation in the Pathogenesis of Liver Disease in Patients With Inborn Errors of Bile Acid Metabolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infantile Refsum's Disease
Zellweger Syndrome
Adrenoleukodystrophy
Peroxisomal Disorders
Cholestasis
Lead sponsor: Mirum Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Children's Hospital Medical Center, Cincinnati
First posted: 2000-12-07
Enrollment: 85
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Excretion of Atypical Bile Acids in Urine by Category
timeFrame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Secondary outcomes:
measure: Change in Liver Function Tests (LFTs) Measured in Serum
timeFrame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
measure: Liver Histology
timeFrame: At baseline (if no historical data were available) and between 1 and 6 months following treatment start.
measure: Height and Weight
timeFrame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
measure: Adverse Events
timeFrame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Other outcomes:
measure: Change in Bilirubin Measured in Serum
timeFrame: Baseline and on treatment (every 1, 3, or 6 months, depending on protocol version, for an average of 2.8 years)
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: James Heubi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Kenneth Setchell, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heubi JE, Bove KE, Setchell KDR. Oral Cholic Acid Is Efficacious and Well Tolerated in Patients With Bile Acid Synthesis and Zellweger Spectrum Disorders. J Pediatr Gastroenterol Nutr. 2017 Sep;65(3):321-326. doi: 10.1097/MPG.0000000000001657.