The REPLACE Registry for Cholbam® (Cholic Acid)
- Registration Number
- NCT03115086
- Lead Sponsor
- Mirum Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 55
- Male and female patients, of any age.
- 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.
- The patient has a diagnosis for which Cholbam is indicated.
- The patient is or will be treated with Cholbam at the time of signing the informed consent form (ICF) (enrollment).
- Patients who, by judgement of the Investigator, will not be able to comply with the requirements of the protocol will be excluded
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Existing User Cholbam Patients who have been using Cholbam for at least 30 days New User Cholbam First-time initiators of Cholbam
- Primary Outcome Measures
Name Time Method 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.
Death 10 Years AEs and SAEs leading to death will be recorded. The relatedness of death to Cholbam or disease progression will be recorded.
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.
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.
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 Outcome Measures
Name Time Method Changes in albumin 10 years Changes in direct bilirubin 10 years Changes in alanine aminotransferase (ALT) 10 years 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.
Age-appropriate developmental milestones in infants 10 years Measured by WHO Motor Development Milestones
Changes in international normalized ratio (INR) 10 years All indications for which Cholbam has been prescribed 10 years Description of all indications for which Cholbam has been prescribed
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.
Changes in prothrombin time (PT) 10 years Presence or absence of urinary bile acids and levels of bile acid intermediaries and urinary bile alcohol 10 years Changes in bilirubin 10 years Changes in aspartate aminotransferase (AST) 10 years Changes in alkaline phosphatase 10 years Changes in gamma-glutamyl transferase (GGT) 10 years
Trial Locations
- Locations (23)
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Kidz Pediatric Multispecialty Group
🇺🇸Hollywood, Florida, United States
Nemours duPont Pediatrics Specialty Clinic
🇺🇸Jacksonville, Florida, United States
Icahn School Of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Stanford School of Medicine
🇺🇸Palo Alto, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Children's Center For Digestive Health
🇺🇸Atlanta, Georgia, United States
The Community Health Clinic
🇺🇸Topeka, Indiana, United States
Washington University at St Louis
🇺🇸Saint Louis, Missouri, United States
Office of Dr. Esperanza Font-Montgomery MD
🇺🇸Columbia, Missouri, United States
UC San Francisco
🇺🇸San Francisco, California, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Monroe-Carell Jr. Children's Hospital at Vanderbilt
🇺🇸Nashville, Tennessee, United States
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Ochsner Hospital for Children
🇺🇸New Orleans, Louisiana, United States
UNC Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Golisano Children's Hospital, URMC
🇺🇸Rochester, New York, United States
Montefiore Medical Center
🇺🇸New York, New York, United States