The REPLACE Registry for Cholbam® (Cholic Acid)

NCT03115086 | Active Not Recruiting FDA Drug

• 1 other identifier: 031CHO15001
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 23

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.

Conditions

Bile Acid Synthesis Disorders

Keywords

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

Outcome Measures

Primary Outcomes (9)

• 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.

  10 Years

• 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.

  10 Years

• 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.

  10 Years

• 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.

  10 Years

• 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.

  10 Years

• Number of participants with growth failure

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

  10 Years

• Death

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

  10 Years

• Adverse effects on pregnancy, pregnancy outcomes, and infant status

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

  10 Years

• All Adverse Events (AEs) and Serious AEs (SAEs)

  All other AEs and SAEs will be collected.

  10 years

Secondary Outcomes (16)

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

  10 years

• Changes from baseline in weight

  10 years

• Changes from baseline in length/height

  10 years

• Changes from baseline in head circumference in infants

  10 years

• Age-appropriate developmental milestones in infants

  10 years

Study Arms (2)

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

Cholbam DRUG

Cholbam prescribed according to the approved label.

Existing User; New User

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients with a diagnosis for which Cholbam is indicated are eligible for inclusion in the Registry.

You may qualify if:

• 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).

You may not qualify if:

• \. Patients who, by judgement of the Investigator, will not be able to comply with the requirements of the protocol will be excluded

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (23)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford School of Medicine

Palo Alto, California, 94305, United States

Location

UC San Francisco

San Francisco, California, 94158, United States

Location

Kidz Pediatric Multispecialty Group

Hollywood, Florida, 33021, United States

Location

Nemours duPont Pediatrics Specialty Clinic

Jacksonville, Florida, 32207, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Children's Center For Digestive Health

Atlanta, Georgia, 30342, United States

Location

The Community Health Clinic

Topeka, Indiana, 46571, United States

Location

Ochsner Hospital for Children

New Orleans, Louisiana, 70121, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55454, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Office of Dr. Esperanza Font-Montgomery MD

Columbia, Missouri, 65201, United States

Location

Washington University at St Louis

St Louis, Missouri, 63110, United States

Location

Icahn School Of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Montefiore Medical Center

New York, New York, 10032, United States

Location

Golisano Children's Hospital, URMC

Rochester, New York, 14642, United States

Location

UNC Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Monroe-Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

MeSH Terms

Conditions

Zellweger Syndrome; Peroxisomal Disorders

Interventions

Cholic Acid

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Sagar A Vaidya, MD, PhD

  Vice President, Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2017
• First Posted: April 14, 2017
• Study Start: July 10, 2017
• Primary Completion (Estimated): July 1, 2038
• Study Completion (Estimated): July 1, 2039
• Last Updated: October 2, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (23)