The REPLACE Registry for Cholbam® (Cholic Acid)

Keywords

• Bile Acid Synthesis Disorder
• Zellweger Spectrum Disorder
• Peroxisomal Disorder
• Cholic Acid
• Cholbam
• The REPLACE Registry

Lead sponsor

Mirum Pharmaceuticals, Inc. is the lead sponsor of 39 studies on the registry; 6 are open to participants now.

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

Study population

Groups and cohorts

• Existing User

  Patients who have been using Cholbam for at least 30 days

  Drug: Cholbam

• New User

  First-time initiators of Cholbam

  Drug: Cholbam

Interventions

• DrugCholbam

  Cholbam prescribed according to the approved label.

Primary outcomes

1. Number of participants with worsening cholestasis

   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.

   Time frame: 10 Years

2. Number of participants with new-onset cholestasis

   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.

   Time frame: 10 Years

3. Number of participants with steatorrhea leading to poor growth

   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.

   Time frame: 10 Years

4. Changes in serum levels of fat-soluble vitamins

   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.

   Time frame: 10 Years

5. Neuropathic signs or symptoms related to fat-soluble vitamin deficiencies

   Neuropathic signs or symptoms related to fat-soluble vitamin deficiencies (peripheral neuropathy, cerebellar ataxia) will be assessed by the Investigator.

   Time frame: 10 Years

6. Number of participants with growth failure

   Growth failure that the physician judges to be attributable to malabsorption.

   Time frame: 10 Years

7. Death

   AEs and SAEs leading to death will be recorded. The relatedness of death to Cholbam or disease progression will be recorded.

   Time frame: 10 Years

8. Adverse effects on pregnancy, pregnancy outcomes, and infant status

   Adverse effects on pregnancy, pregnancy outcomes, and infant status will be recorded.

   Time frame: 10 Years

9. All Adverse Events (AEs) and Serious AEs (SAEs)

   All other AEs and SAEs will be collected.

   Time frame: 10 years

Secondary outcomes

1. Changes in Cholbam dosing regimens and reasons for any dose modifications or treatment discontinuations

   Time frame: 10 years

2. Changes from baseline in weight

   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.

   Time frame: 10 years

3. Changes from baseline in length/height

   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.

   Time frame: 10 years

4. Changes from baseline in head circumference in infants

   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.

   Time frame: 10 years

5. Age-appropriate developmental milestones in infants

   Measured by WHO Motor Development Milestones

   Time frame: 10 years

6. Changes in prothrombin time (PT)

   Time frame: 10 years

7. Changes in international normalized ratio (INR)

   Time frame: 10 years

8. Changes in albumin

   Time frame: 10 years

9. Changes in bilirubin

   Time frame: 10 years

10. Changes in direct bilirubin

    Time frame: 10 years

11. Changes in alanine aminotransferase (ALT)

    Time frame: 10 years

12. Changes in aspartate aminotransferase (AST)

    Time frame: 10 years

13. Changes in gamma-glutamyl transferase (GGT)

    Time frame: 10 years

14. Changes in alkaline phosphatase

    Time frame: 10 years

15. Presence or absence of urinary bile acids and levels of bile acid intermediaries and urinary bile alcohol

    Time frame: 10 years

16. All indications for which Cholbam has been prescribed

    Description of all indications for which Cholbam has been prescribed

    Time frame: 10 years

Individual participant data

Plan to share: No