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CompletedNCT00007020Updated Oct 3, 2023Results posted

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

A Phase 3 interventional study of Cholic Acids in Infantile Refsum's Disease, Zellweger Syndrome and Adrenoleukodystrophy, sponsored by Mirum Pharmaceuticals, Inc.. Completed at 1 site in United States. Per ClinicalTrials.gov, last updated 2023-10-03.

Sponsored by Mirum Pharmaceuticals, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
85
Allocation
Not applicable
Sex
All
01

Study 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

Read the 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
02

Conditions studied

  • Infantile Refsum's Disease
  • Zellweger Syndrome
  • Adrenoleukodystrophy
  • Peroxisomal Disorders
  • Cholestasis
03

In context

Adrenoleukodystrophy

68 studies on the registry are indexed under Adrenoleukodystrophy; 19 are open to participants now.

This study's enrollment of 85 is above the median of 31 across 40 interventional studies indexed under Adrenoleukodystrophy.

Browse Adrenoleukodystrophy studies →

Lead sponsor

Mirum Pharmaceuticals, Inc. is the lead sponsor of 40 studies on the registry; 7 are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.

Browse Mirum Pharmaceuticals, Inc. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

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 > 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 document before study start.
  • The patient must be willing and able to comply with all study assessments and procedures.
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
85 participants (actual)

Study arms

  • Other
    Cholic Acid

    Drug: Cholic Acids

Interventions

  • DrugCholic Acids

    10-15 mg/kg body weight/day taken orally.

    Also known as: Cholic, Cholic Acid, Cholic Acid Capsules

06

What researchers measure

Primary outcomes

  1. 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)

    Time frame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years

Secondary outcomes

  1. 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)

    Time frame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years

  2. 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).

    Time frame: At baseline (if no historical data were available) and between 1 and 6 months following treatment start.

  3. 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

    Time frame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years

  4. Adverse Events

    Number of patients with any adverse event

    Time frame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years

Other outcomes

  1. Change in Bilirubin Measured in Serum

    Bilirubin concentration in serum at baseline and on treatment

    Time frame: Baseline and on treatment (every 1, 3, or 6 months, depending on protocol version, for an average of 2.8 years)

07

Results

Posted Jul 15, 2020
Limitations and caveats
CAC-91-10-10 includes data from patients enrolled from 1992-2009. The study end date was arbitrarily chosen as data cut-off point; the disease requires life-long treatment, no final study visit was done. Many patients continued onto study CAC-002-01

Participant flow

A total of 85 patients were enrolled.

Participant flow — Overall Study
MilestoneCholic Acid
Started85
Completed41
Not completed44
Withdrew: Death16
Withdrew: Lost to follow-up13
Withdrew: Pt withdrawn (worsening cholestasis)1
Withdrew: Pt withdrawn (liver transplant)4
Withdrew: Pt cared for by outside physician4
Withdrew: No evidence of treatment6

Outcome measures

PrimaryNumber 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)

Time frame:
Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Reported as:
Count of participants · Participants
Number of Participants With Excretion of Atypical Bile Acids in Urine by Category
ParticipantsCholic Acid
Baseline, no atypical bile acid excretion10
On treatment, no atypical bile acid excretion51
Baseline, slight atypical bile acid excretion11
On treatment, slight atypical bile acid excretion9
Baseline, significant atypical bile acid excretion16
OT, significant atypical bile acid excretion4
Baseline, marked atypical bile acid excretion33
On treatment, marked atypical bile acid excretion6
SecondaryChange 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)

Time frame:
Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Reported as:
Count of participants · Participants
Change in Liver Function Tests (LFTs) Measured in Serum
ParticipantsCholic Acid
Baseline, ALT <ULN14
On treatment, ALT <ULN49
Baseline, ULN ≤ ALT <2 x ULN16
On treatment, ULN ≤ ALT <2 x ULN13
Baseline, 2 ULN ≤ ALT <3 x ULN8
On treatment, 2 ULN ≤ ALT <3 x ULN2
Baseline, ALT ≥3 x ULN29
On treatment, ALT ≥3 x ULN3
Baseline, AST <ULN9
On treatment, AST <ULN38
Baseline, ULN ≤ AST <2 x ULN14
On treatment, ULN ≤ AST <2 x ULN15
Baseline, 2 ULN ≤ AST <3 x ULN7
On treatment, 2 ULN ≤ AST <3 x ULN4
Baseline, AST ≥3 x ULN35
On treatment, AST ≥3 x ULN9
SecondaryLiver 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).

Time frame:
At baseline (if no historical data were available) and between 1 and 6 months following treatment start.
Reported as:
Count of participants · Participants
Liver Histology
ParticipantsCholic Acid
Periportal inflammation at BL, qualitative19
Periportal inflammation OT, qualitative16
Lobular inflammation at BL, qualitative5
Lobular inflammation OT, qualitative4
Inflammation (not spec.) at BL, qualitative3
Inflammation (not spec.) OT, qualitative0
Bridging fibrosis at BL, qualitative25
Bridging fibrosis OT, qualitative31
Fibrosis (not specified) at BL, qualitative6
Fibrosis (not specified) OT, qualitative6
Cholestasis at BL, qualitative20
Cholestasis OT, qualitative10
Giant cells at BL, qualitative18
Giant cells OT, qualitative12
Necrosis at BL, qualitative14
Necrosis OT, qualitative2
Periportal inflammation at BL, quantitative18
Periportal inflammation OT, quantitative15
Lobular inflammation at BL, quantitative5
Lobular inflammation OT, quantitative4
Inflammation (not specified) at BL, quantitative3
Inflammation (not specified) OT, quantitative0
Bridging fibrosis at baseline, quantitative22
Bridging fibrosis OT, quantitative27
Fibrosis (not specified) at BL, quantitative3
Fibrosis (not specified) OT, quantitative5
Cholestasis at BL, quantitative15
Cholestasis OT, quantitative7
Giant cells at BL, quantitative13
Giant cells OT, quantitative9
Necrosis at BL, quantitative13
Necrosis OT, quantitative2
SecondaryHeight 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

Time frame:
Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Reported as:
Mean · Percentile
Height and Weight
PercentileCholic Acid
Height percentile, baseline30.1 ± 5.5
Height percentile, on treatment44.0 ± 6.1
Weight percentile, baseline21.3 ± 3.7
Weight percentile, on treatment42.3 ± 4.8
SecondaryAdverse Events

Number of patients with any adverse event

Time frame:
Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Reported as:
Count of participants · Participants
Adverse Events
ParticipantsCholic Acid
Patients at risk79
Patients with any AE38
Other pre-specifiedChange in Bilirubin Measured in Serum

Bilirubin concentration in serum at baseline and on treatment

Time frame:
Baseline and on treatment (every 1, 3, or 6 months, depending on protocol version, for an average of 2.8 years)
Reported as:
Mean · mg/dL
Change in Bilirubin Measured in Serum
mg/dLCholic Acid
Baseline, bilirubin0.3
On treatment, bilirubin0.6 ± 0.5
Baseline, direct bilirubin2.2 ± 5.6
On treatment, direct bilirubin0.5 ± 1.8
Baseline, indirect bilirubin0.5 ± 0.9
On treatment, indirect bilirubin0.2 ± 0.2
Baseline, total bilirubin2.8 ± 10.6
On treatment, total bilirubin1.5 ± 5.2

Adverse events

Collected over Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cholic Acid13/79 (16.5%)20/79 (25.3%)35/79 (44.3%)
Most frequent serious events
Showing 10 of 19
Most frequent serious events
EventCholic Acid
Disease progressionGeneral disorders7/79
DiarrhoeaGastrointestinal disorders2/79
DehydrationMetabolism and nutrition disorders2/79
Urinary tract infectionInfections and infestations2/79
Nutritional condition abnormalInvestigations1/79
EpistaxisRespiratory, thoracic and mediastinal disorders1/79
Respiratory disorderRespiratory, thoracic and mediastinal disorders1/79
Respiratory distressRespiratory, thoracic and mediastinal disorders1/79
CoagulopathyBlood and lymphatic system disorders1/79
ConvulsionNervous system disorders1/79
Most frequent other events
Showing 10 of 53
Most frequent other events
EventCholic Acid
PyrexiaGeneral disorders7/79
Upper respiratory tract infectionInfections and infestations5/79
FractureInjury, poisoning and procedural complications4/79
ConvulsionNervous system disorders4/79
DiarrhoeaGastrointestinal disorders4/79
LethargyNervous system disorders3/79
CoughRespiratory, thoracic and mediastinal disorders2/79
EpistaxisRespiratory, thoracic and mediastinal disorders2/79
Abdominal painGastrointestinal disorders2/79
AscitesGastrointestinal disorders2/79

Baseline characteristics

Age, Continuous
Age, Continuous(years)Cholic Acid
Mean3 ± 4
Sex: Female, Male
Sex: Female, Male(Participants)Cholic Acid
Female31
Male50
Region of Enrollment
Region of Enrollment(Participants)Cholic Acid
United States85
08

Study locations

1 site
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229-3039, United States
09

References and documents

Publications

  • 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. PubMed 28644367 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 3, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00007020
Lead sponsor
Mirum Pharmaceuticals, Inc.
Collaborators
Children's Hospital Medical Center, Cincinnati
Responsible party
Sponsor
First posted
Dec 7, 2000
Start date
Jan 1992
Primary completion
Dec 2009
Completion
Dec 2009
Results posted
Jul 15, 2020
Last update
Oct 3, 2023

Study contacts

James Heubi, MD
principal investigator · Children's Hospital Medical Center, Cincinnati
Kenneth Setchell, PhD
principal investigator · Children's Hospital Medical Center, Cincinnati

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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