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

• ClinicalTrials.gov Identifier: NCT00007020
• Recruitment Status: Completed
• First Posted: December 7, 2000
• Results First Posted: July 15, 2020
• Last Update Posted: October 5, 2020
• Sponsor: Travere Therapeutics, Inc.
• Collaborator: Children's Hospital Medical Center, Cincinnati
• Information provided by (Responsible Party): Travere Therapeutics, Inc.

Study Description

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

Condition or disease	Intervention/treatment	Phase
Infantile Refsum's Disease; Zellweger Syndrome; Adrenoleukodystrophy; Peroxisomal Disorders; Cholestasis	Drug: Cholic Acids	Phase 3

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Investigation in the Pathogenesis of Liver Disease in Patients With Inborn Errors of Bile Acid Metabolism
• Study Start Date: January 1992
• Actual Primary Completion Date: December 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Cholic Acid	Drug: Cholic Acids; 10-15 mg/kg body weight/day taken orally.; Other Names: Cholic; Cholic Acid; Cholic Acid Capsules

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Excretion of Atypical Bile Acids in Urine by Category [ Time Frame: 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 :

1. Change in Liver Function Tests (LFTs) Measured in Serum [ Time Frame: 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)
2. Liver Histology [ Time Frame: 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).
3. Height and Weight [ Time Frame: 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
4. Adverse Events [ Time Frame: 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

Other Outcome Measures:

1. Change in Bilirubin Measured in Serum [ Time Frame: Baseline and on treatment (every 1, 3, or 6 months, depending on protocol version, for an average of 2.8 years) ]
   Bilirubin concentration in serum at baseline and on treatment

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229-3039

Sponsors and Collaborators

Travere Therapeutics, Inc.

Children's Hospital Medical Center, Cincinnati

Investigators

• Principal Investigator: James Heubi, MD; Children's Hospital Medical Center, Cincinnati
• Principal Investigator: Kenneth Setchell, PhD; Children's Hospital Medical Center, Cincinnati

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Travere Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT00007020
• Other Study ID Numbers: CAC-91-10-10; CCHMC-91-10-10 ( Other Identifier: Cincinnati Children's Hospital Medical Center ); NCRR-M01RR08084-0009 ( Other Identifier: National Center For Research Resources (NCRR) )
• First Posted: December 7, 2000
• Results First Posted: July 15, 2020
• Last Update Posted: October 5, 2020
• Last Verified: September 2020

Additional relevant MeSH terms:

Cholestasis; Zellweger Syndrome; Adrenoleukodystrophy; Refsum Disease; Refsum Disease, Infantile; Peroxisomal Disorders; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Hereditary Sensory and Motor Neuropathy