Bile Acid Synthesis Disorders
Conditions
Keywords
Bile Acid Synthesis Disorder, Zellweger Spectrum Disorder, Peroxisomal Disorder, Cholic Acid, Cholbam, The REPLACE Registry
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.
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.
Interventions
DRUGCholbam
Cholbam prescribed according to the approved label.
Sponsors
Mirum Pharmaceuticals, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with worsening cholestasis | 10 Years | 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. |
| Number of participants with new-onset cholestasis | 10 Years | 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. |
| Number of participants with steatorrhea leading to poor growth | 10 Years | 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. |
| Changes in serum levels of fat-soluble vitamins | 10 Years | 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. |
| Neuropathic signs or symptoms related to fat-soluble vitamin deficiencies | 10 Years | Neuropathic signs or symptoms related to fat-soluble vitamin deficiencies (peripheral neuropathy, cerebellar ataxia) will be assessed by the Investigator. |
| Number of participants with growth failure | 10 Years | Growth failure that the physician judges to be attributable to malabsorption. |
| Death | 10 Years | AEs and SAEs leading to death will be recorded. The relatedness of death to Cholbam or disease progression will be recorded. |
| Adverse effects on pregnancy, pregnancy outcomes, and infant status | 10 Years | Adverse effects on pregnancy, pregnancy outcomes, and infant status will be recorded. |
| All Adverse Events (AEs) and Serious AEs (SAEs) | 10 years | All other AEs and SAEs will be collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Cholbam dosing regimens and reasons for any dose modifications or treatment discontinuations | 10 years | — |
| Changes from baseline in weight | 10 years | 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. |
| Changes from baseline in length/height | 10 years | 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. |
| Changes from baseline in head circumference in infants | 10 years | 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. |
| Age-appropriate developmental milestones in infants | 10 years | Measured by WHO Motor Development Milestones |
| Changes in prothrombin time (PT) | 10 years | — |
| Changes in international normalized ratio (INR) | 10 years | — |
| Changes in albumin | 10 years | — |
| Changes in bilirubin | 10 years | — |
| Changes in direct bilirubin | 10 years | — |
| Changes in alanine aminotransferase (ALT) | 10 years | — |
| Changes in aspartate aminotransferase (AST) | 10 years | — |
| Changes in gamma-glutamyl transferase (GGT) | 10 years | — |
| Changes in alkaline phosphatase | 10 years | — |
| Presence or absence of urinary bile acids and levels of bile acid intermediaries and urinary bile alcohol | 10 years | — |
| All indications for which Cholbam has been prescribed | 10 years | Description of all indications for which Cholbam has been prescribed |
Countries
United States
Contacts
STUDY_DIRECTORSagar A Vaidya, MD, PhD
Vice President, Clinical Development
Outcome results
None listed