Bile Acid Synthesis DefectPhase 3NCT01438411
Open Label, Continuation Study of Cholic Acid in Subjects With Inborn Errors of Bile Acid Synthesis
A Phase 3 study testing Cholic Acid in people with Bile Acid Synthesis Defect, run by Mirum Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
The primary purpose of the study is to evaluate the therapeutic efficacy and safety of cholic acid in subjects with identified inborn errors of bile acid synthesis. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Bile Acid Synthesis Defect
- What is being tested?
- Cholic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Jul 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects who received cholic acid through CCHMC protocols 91-10-10 or CAC-002-01 and meet the following criteria are eligible for study participation.
- The subject and/or parent/legal guardian must have provided informed consent prior to study start.
- The subject must have a diagnosis of an inborn error of bile acid synthesis.
- The subject must be willing and able to comply with all study assessments and procedures.
- Subjects with other organ dysfunction will not be excluded
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: An Open Label, Single Center, Nonrandomized Continuation Study of Cholic Acid Capsules to Treat Subjects With Inborn Errors of Bile Acid Synthesis
The primary purpose of the study is to evaluate the therapeutic efficacy and safety of cholic acid in subjects with identified inborn errors of bile acid synthesis.
Read the detailed description
This is a Phase 3, open-label, single center, nonrandomized study. This continuation protocol will consist of eligible subjects who have previously received cholic acid through the Cincinnati Children's Hospital Medical Center (CCHMC) Compassionate Use (91-10-10), CAC-001-01 study protocols and newly diagnosed subjects.
New subjects will be infants, children, adolescents identified from urine samples obtained from the clinical services of programs across the U.S., Canada, South America, Europe, and Asia. Subject or their legal representative will receive information regarding the study, and the principle investigator (PI) or designee will obtain informed consent. Serum and urine samples will be collected and sent to CCHMC to measure complete bile acid profile analysis. Clinical records including medical history, physical exams, vital signs, and laboratory assessments performed as standard of care will be reviewed to ensure subject eligibility and determine baseline values.
Subjects who have participated in Protocols conducted under IND 45,470 will be consented to continue to receive cholic acid capsules under this continuation protocol. Subjects will serve as their own controls and no placebo will be utilized.
- Conditions
- Bile Acid Synthesis Defect
- Being tested
- Cholic Acid
- Keywords
- Cholic Acid, Inborn Error, Bile Acid Metabolism, Inborn Error of Bile Acid Synthesis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cholic AcidDrug
Also called Cholic, Cholic Acid Capsules
10-15 mg/kg body weight/day supplied in 50 or 250 mg Cholic Acid Capsules
| Study group | Role | What they receive |
|---|---|---|
| Cholic Acid | Other | Active drug Receives: Drug: Cholic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Atypical Urinary Bile Acid Excretion by FAB-MS (Fast-Atom-Bombardment Ionization-Mass Spectrometry)
The level of atypical urinary bile acid secretion was scored using a scale of: 0, normal; 1, slight; 2, significant; or 3, marked. A Cochran-Mantel-Haenszel (CMH) test with modified ridit scoring was used to compare the difference between the score at baseline and the worst post-baseline score during treatment with cholic acid in this single-arm trial.
Measured: At baseline, then every 12 months for an average of 3.5 years
Secondary outcomes (9)
Evaluation of Serum Transaminases: ALT
Changes in ALT were evaluated in terms of elevations above the upper limit of normal (ULN) and were categorized as: <ULN; ≥1 ULN but <2 ULN; ≥2 ULN but <3 ULN; and ≥3x ULN. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented.
Measured: At baseline, then every 12 months for an average of 3.5 years
Evaluation of Serum Transaminases: AST
Changes in AST were evaluated in terms of elevations above the upper limit of normal (ULN) and were categorized as: <ULN; ≥1 ULN but <2 ULN; ≥2 ULN but <3 ULN; and ≥3x ULN. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented.
Measured: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Bilirubin
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for bilirubin. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
Measured: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Gamma Glutamyl Transferase (GGT)
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for GGT. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
Measured: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Alkaline Phosphatase
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for alkaline phosphatase. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
Measured: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Prothrombin Time
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for prothrombin time. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
Measured: At baseline, then every 12 months for an average of 3.5 years
Physical Examinations: Height
Changes in height percentiles from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial.
Measured: At baseline, then every 12 months for an average of 3.5 years
Physical Examinations: Body Weight
Changes in body weight percentiles from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial.
Measured: At baseline, then every 12 months for an average of 3.5 years
Incidence of Adverse Events
Number (%) of patients with any AE
Measured: At baseline, then every 12 months for an average of 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2011 (estimated)
- Study startJan 2010
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bile Acid Synthesis DefectStudies of the same condition, open and under way.
- More trials run by Mirum Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirum Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James E Heubi, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiKenneth Setchell, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01438411
- Sponsor's protocol ID
- CAC-002-01
- Status last verified
- Sep 2023
- First submitted
- 20 Sep 2011
- Last updated
- 3 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Heubi JE, Setchell KDR. Open-label Phase 3 Continuation Study of Cholic Acid in Patients With Inborn Errors of Bile Acid Synthesis. J Pediatr Gastroenterol Nutr. 2020 Apr;70(4):423-429. doi: 10.1097/MPG.0000000000002618.
PubMed 31899729
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single Center, Nonrandomized Continuation Study of Cholic Acid Capsules to Treat Subjects With Inborn Errors of Bile Acid Synthesis
- ClinicalTrials.gov ID
- NCT01438411
- Acronym / sponsor ID
- CAC-002-01
- Conditions
- Bile Acid Synthesis Defect
- Keywords
- Cholic Acid, Inborn Error, Bile Acid Metabolism, Inborn Error of Bile Acid Synthesis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Mirum Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2010
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 22 Sep 2011 (estimated)
- Results
- Posted 21 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of the study is to evaluate the therapeutic efficacy and safety of cholic acid in subjects with identified inborn errors of bile acid synthesis.
Detailed description
This is a Phase 3, open-label, single center, nonrandomized study. This continuation protocol will consist of eligible subjects who have previously received cholic acid through the Cincinnati Children's Hospital Medical Center (CCHMC) Compassionate Use (91-10-10), CAC-001-01 study protocols and newly diagnosed subjects.
New subjects will be infants, children, adolescents identified from urine samples obtained from the clinical services of programs across the U.S., Canada, South America, Europe, and Asia. Subject or their legal representative will receive information regarding the study, and the principle investigator (PI) or designee will obtain informed consent. Serum and urine samples will be collected and sent to CCHMC to measure complete bile acid profile analysis. Clinical records including medical history, physical exams, vital signs, and laboratory assessments performed as standard of care will be reviewed to ensure subject eligibility and determine baseline values.
Subjects who have participated in Protocols conducted under IND 45,470 will be consented to continue to receive cholic acid capsules under this continuation protocol. Subjects will serve as their own controls and no placebo will be utilized.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cholic Acid | Other | Drug: Cholic AcidActive drug |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Subjects who received cholic acid through CCHMC protocols 91-10-10 or CAC-002-01 and meet the following criteria are eligible for study participation.
- The subject and/or parent/legal guardian must have provided informed consent prior to study start.
- The subject must have a diagnosis of an inborn error of bile acid synthesis.
- The subject must be willing and able to comply with all study assessments and procedures.
- Subjects with other organ dysfunction will not be excluded
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cholic AcidAlso: Cholic, Cholic Acid Capsules10-15 mg/kg body weight/day supplied in 50 or 250 mg Cholic Acid Capsules | Drug | Cholic Acid |
Primary outcome
Change in Atypical Urinary Bile Acid Excretion by FAB-MS (Fast-Atom-Bombardment Ionization-Mass Spectrometry)
Time frame: At baseline, then every 12 months for an average of 3.5 years
The level of atypical urinary bile acid secretion was scored using a scale of: 0, normal; 1, slight; 2, significant; or 3, marked. A Cochran-Mantel-Haenszel (CMH) test with modified ridit scoring was used to compare the difference between the score at baseline and the worst post-baseline score during treatment with cholic acid in this single-arm trial.
9 secondary outcomes
Evaluation of Serum Transaminases: ALT
Time frame: At baseline, then every 12 months for an average of 3.5 years
Evaluation of Serum Transaminases: AST
Time frame: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Bilirubin
Time frame: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Gamma Glutamyl Transferase (GGT)
Time frame: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Alkaline Phosphatase
Time frame: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Prothrombin Time
Time frame: At baseline, then every 12 months for an average of 3.5 years
Physical Examinations: Height
Time frame: At baseline, then every 12 months for an average of 3.5 years
Physical Examinations: Body Weight
Time frame: At baseline, then every 12 months for an average of 3.5 years
Incidence of Adverse Events
Time frame: At baseline, then every 12 months for an average of 3.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31899729Heubi JE, Setchell KDR. Open-label Phase 3 Continuation Study of Cholic Acid in Patients With Inborn Errors of Bile Acid Synthesis. J Pediatr Gastroenterol Nutr. 2020 Apr;70(4):423-429. doi: 10.1097/MPG.0000000000002618.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James E Heubi, MD principal investigator
Children's Hospital Medical Center, Cincinnati
Kenneth Setchell, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cholic Acid in people with Bile Acid Synthesis Defect, run by Mirum Pharmaceuticals, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Atypical Urinary Bile Acid Excretion by FAB-MS (Fast-Atom-Bombardment Ionization-Mass Spectrometry) (time frame: At baseline, then every 12 months for an average of 3.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01438411, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2023.