Brief Summary
This is a prospective, observational, non-interventional patient registry study designed to document product safety and effectiveness outcomes for 10 years in patients treated with Cholbam, including those who have been using Cholbam for at least 30 days (existing users) and those who are first-time initiators of Cholbam.
Brief Title
The REPLACE Registry for Cholbam® (Cholic Acid)
Detailed Description
No experimental intervention is involved. Patients in the Registry undergo clinical assessments and receive care as determined by the patient's treating physician.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Bile Acid Synthesis Disorders
Eligibility Criteria
Inclusion Criteria:
1. Male and female patients, of any age.
2. The patient and/or the patient's parent/legal guardian is willing and able to provide signed informed consent, and the patient, if less than 18 years of age, is willing to provide assent as appropriate and in accordance with local regulatory, IRB, and EC requirements.
3. The patient has a diagnosis for which Cholbam is indicated.
4. The patient is or will be treated with Cholbam at the time of signing the informed consent form (ICF) (enrollment).
Exclusion Criteria:
1. Patients who, by judgement of the Investigator, will not be able to comply with the requirements of the protocol will be excluded
1. Male and female patients, of any age.
2. The patient and/or the patient's parent/legal guardian is willing and able to provide signed informed consent, and the patient, if less than 18 years of age, is willing to provide assent as appropriate and in accordance with local regulatory, IRB, and EC requirements.
3. The patient has a diagnosis for which Cholbam is indicated.
4. The patient is or will be treated with Cholbam at the time of signing the informed consent form (ICF) (enrollment).
Exclusion Criteria:
1. Patients who, by judgement of the Investigator, will not be able to comply with the requirements of the protocol will be excluded
Inclusion Criteria
Inclusion Criteria:
1. Male and female patients, of any age.
2. The patient and/or the patient's parent/legal guardian is willing and able to provide signed informed consent, and the patient, if less than 18 years of age, is willing to provide assent as appropriate and in accordance with local regulatory, IRB, and EC requirements.
3. The patient has a diagnosis for which Cholbam is indicated.
4. The patient is or will be treated with Cholbam at the time of signing the informed consent form (ICF) (enrollment).
1. Male and female patients, of any age.
2. The patient and/or the patient's parent/legal guardian is willing and able to provide signed informed consent, and the patient, if less than 18 years of age, is willing to provide assent as appropriate and in accordance with local regulatory, IRB, and EC requirements.
3. The patient has a diagnosis for which Cholbam is indicated.
4. The patient is or will be treated with Cholbam at the time of signing the informed consent form (ICF) (enrollment).
Gender
All
Gender Based
false
Keywords
Bile Acid Synthesis Disorder
Zellweger Spectrum Disorder
Peroxisomal Disorder
Cholic Acid
Cholbam
The REPLACE Registry
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
NCT Id
NCT03115086
Org Class
Industry
Org Full Name
Mirum Pharmaceuticals, Inc.
Org Study Id
031CHO15001
Overall Status
Active, not recruiting
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Prospective, Observational, Non-Interventional, Post-Marketing, Patient Registry to Collect Data on Routine Clinical Care in Patients Treated With Cholbam® (Cholic Acid)
Primary Outcomes
Outcome Description
Worsening cholestasis will be identified by measuring direct total bilirubin concentration in blood and will be defined as a 25% increase from previous measurement if the total bilirubin is \>1mg/dL.
Outcome Measure
Number of participants with worsening cholestasis
Outcome Time Frame
10 Years
Outcome Description
Patients with new-onset cholestasis will be identified by detecting abnormal direct bilirubin concentration \>1mg/dL or direct bilirubin greater than 20% of the total bilirubin if total bilirubin is \>5mg/dL.
Outcome Measure
Number of participants with new-onset cholestasis
Outcome Time Frame
10 Years
Outcome Description
Steatorrhea leading to poor growth in children, which will be defined as a decrease in growth percentiles from the original percentile at enrollment to the registry study.
Outcome Measure
Number of participants with steatorrhea leading to poor growth
Outcome Time Frame
10 Years
Outcome Description
Fat-soluble vitamin (A, D, E, K) deficiencies will be identified by comparing results from serum assays (Vitamin A: Retinol, Vitamin D: 250HD2 + 250HD3, Vitamin K: Serum Vitamin K, Vitamin E: Serum Vitamin E) for each vitamin with standard ranges.
Outcome Measure
Changes in serum levels of fat-soluble vitamins
Outcome Time Frame
10 Years
Outcome Description
Neuropathic signs or symptoms related to fat-soluble vitamin deficiencies (peripheral neuropathy, cerebellar ataxia) will be assessed by the Investigator.
Outcome Measure
Neuropathic signs or symptoms related to fat-soluble vitamin deficiencies
Outcome Time Frame
10 Years
Outcome Description
Growth failure that the physician judges to be attributable to malabsorption.
Outcome Measure
Number of participants with growth failure
Outcome Time Frame
10 Years
Outcome Description
AEs and SAEs leading to death will be recorded. The relatedness of death to Cholbam or disease progression will be recorded.
Outcome Measure
Death
Outcome Time Frame
10 Years
Outcome Description
Adverse effects on pregnancy, pregnancy outcomes, and infant status will be recorded.
Outcome Measure
Adverse effects on pregnancy, pregnancy outcomes, and infant status
Outcome Time Frame
10 Years
Outcome Description
All other AEs and SAEs will be collected.
Outcome Measure
All Adverse Events (AEs) and Serious AEs (SAEs)
Outcome Time Frame
10 years
Secondary Outcomes
Outcome Time Frame
10 years
Outcome Measure
Changes in Cholbam dosing regimens and reasons for any dose modifications or treatment discontinuations
Outcome Description
For patients aged 18 years of or less, these data will be converted into Z-scores based on the WHO growth standards for infants aged 0-2 years and the Centers for Disease Control and Prevention growth standards for children 2-20 years. Growth failure will be defined as a decrease in percentiles from the original percentile at entry point into the registry study.
Outcome Time Frame
10 years
Outcome Measure
Changes from baseline in weight
Outcome Description
For patients aged 18 years of or less, these data will be converted into Z-scores based on the WHO growth standards for infants aged 0-2 years and the Centers for Disease Control and Prevention growth standards for children 2-20 years. Some patients will be adult or will have achieved final height. Growth failure will be defined as a decrease in percentiles from the original percentile at entry point into the registry study.
Outcome Time Frame
10 years
Outcome Measure
Changes from baseline in length/height
Outcome Description
For patients aged 18 years of or less, these data will be converted into Z-scores based on the WHO growth standards for infants aged 0-2 years and the Centers for Disease Control and Prevention growth standards for children 2-20 years. Growth failure will be defined as a decrease in percentiles from the original percentile at entry point into the registry study.
Outcome Time Frame
10 years
Outcome Measure
Changes from baseline in head circumference in infants
Outcome Description
Measured by WHO Motor Development Milestones
Outcome Time Frame
10 years
Outcome Measure
Age-appropriate developmental milestones in infants
Outcome Time Frame
10 years
Outcome Measure
Changes in prothrombin time (PT)
Outcome Time Frame
10 years
Outcome Measure
Changes in international normalized ratio (INR)
Outcome Time Frame
10 years
Outcome Measure
Changes in albumin
Outcome Time Frame
10 years
Outcome Measure
Changes in bilirubin
Outcome Time Frame
10 years
Outcome Measure
Changes in direct bilirubin
Outcome Time Frame
10 years
Outcome Measure
Changes in alanine aminotransferase (ALT)
Outcome Time Frame
10 years
Outcome Measure
Changes in aspartate aminotransferase (AST)
Outcome Time Frame
10 years
Outcome Measure
Changes in gamma-glutamyl transferase (GGT)
Outcome Time Frame
10 years
Outcome Measure
Changes in alkaline phosphatase
Outcome Time Frame
10 years
Outcome Measure
Presence or absence of urinary bile acids and levels of bile acid intermediaries and urinary bile alcohol
Outcome Description
Description of all indications for which Cholbam has been prescribed
Outcome Time Frame
10 years
Outcome Measure
All indications for which Cholbam has been prescribed
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Study Population
All patients with a diagnosis for which Cholbam is indicated are eligible for inclusion in the Registry.
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nadia Ovchinsky
Investigator Email
NOVCHINS@montefiore.org