An Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Pediatric Subjects With Alagille Syndrome

NCT02117713 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LUM001-305SHP625-305
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 11

Brief Summary

This is a multicentre, extension study of LUM001 in children diagnosed with Alagille Syndrome who have completed participation in a core LUM001 treatment protocol. The primary objective is to evaluate long-term safety and tolerability of LUM001. Efficacy will be assessed by evaluating the effect of LUM001 on the biochemical markers and pruritus associated with Alagille Syndrome.

Conditions

Alagille Syndrome

Outcome Measures

Primary Outcomes (1)

• Change From MRX Baseline to Week 48 in Fasting Serum Bile Acid (sBA)

  This primacy efficacy endpoint is the mean change from MRX baseline to week 48 in fasting sBA levels.

  Baseline to Week 48

Secondary Outcomes (10)

• Change From MRX Baseline to Week 216 in Fasting Serum Bile Acid (sBA)

  Baseline to week 216

• Change From Baseline to Week 218 in Pruritus

  Baseline to Week 218

• Change From Baseline to Week 216 in Alanine Aminotransferase

  Baseline to week 216

• Change From Baseline to End of Treatment in Alkaline Phosphatase

  Baseline to Week 216

• Change From MRX Baseline to Week 216 in Aspartate Aminotransferase

  Baseline to week 216

Study Arms (1)

LUM001 (Maralixibat)

EXPERIMENTAL

Participant will receive LUM001 also known as Maralixibat (MRX) administered orally once per day.

Drug: LUM001 (Maralixibat)

Interventions

LUM001 (Maralixibat) DRUG

Dosing of LUM001 also known as Maralixibat (MRX) with the objective of achieving optimal control of pruritus at a dose level that is tolerated by the participant and up to a maximum daily dose of 280 micrograms per kilogram (mcg/kg).

LUM001 (Maralixibat)

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female, 12 months to 18 years of age.
• Competent to provide informed consent and assent (per institutional review board/Ethics Committee \[IRB/EC\]), as appropriate.
• Completed participation in the LUM001-301 protocol.
• Females of childbearing potential must have a negative urine pregnancy test \[beta human chorionic gonadotropin (beta-hCG)\] at the Baseline Visit.
• Sexually active females must be prepared to use an effective method of contraception during the trial.
• Effective methods of contraception are considered to be:
• Hormonal (for example, contraceptive pill, patch, intramuscular implant or injection); or
• Barrier method, for example, (a) condom with spermicide, or (b) diaphragm, with spermicide; or
• Intrauterine device (IUD).
• Participants above the age of assent and caregivers and children must be able to read and understand English or Spanish.
• Caregivers (and age appropriate participants) must have access to phone for scheduled calls from study site.
• Caregivers (and age appropriate participants) must be willing and able to complete a daily electronic diary (ItchRO) during the first consecutive 12 weeks of the study and then for 4 consecutive weeks following the Week 24 and Week 44 visits.
• Caregivers (and age appropriate participants) must digitally accept the licensing agreement in the ItchRO electronic diary software at the outset of the study.
• Eligible participants must be able to adhere to local Ethics Committee or Institutional Review Board (IRB) blood volume limits for laboratory testing.
• The participant has completed the protocol either through Week 144, or the End of Trial visit, or has received permission from the sponsor and the Premier Medical monitor to re-enter the study in the long-term, optional follow-up treatment period 2.

You may not qualify if:

• Experienced an adverse event or serious adverse event (SAE) related to the study drug during the LUM001-301 protocol that led to the discontinuation of the participant from the core study.
• Any conditions or abnormalities (including laboratory abnormalities) which in the opinion of the Investigator, Medical Monitor or ChiLDReN Protocol Chair, may compromise the safety of the participant, or interfere with the participant participating in or completing the study.
• History or known presence of gallstones or kidney stones.
• History of non-adherence during the participant's participation in the LUM001-301 protocol. Non-adherence is defined by dosing compliance (dosing compliance is calculated by \[the total number of doses that were actually taken by the participant\] divided by \[the total number of doses that should have been taken by the participant\] multiplied by 100) of less than 80% in the LUM001-301 protocol.
• Unlikely to comply with the study protocol, or unsuitable for any other reason, as judged by the investigator.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead
• Lumena Pharmaceuticals, Inc.: collaborator
• Childhood Liver Disease Research and Education Network: collaborator

Study Sites (11)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California at San Francisco Children's Hospital

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19147, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Baylor College of Medicine/Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Alagille Syndrome

Interventions

maralixibat

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Limitations and Caveats

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Results Point of Contact

• Title: Mirum Clinical Trials
• Organization: Mirum Pharmaceuticals

medinfo@mirumpharma.com

650-667-4085

Study Officials

• Study Director

  Mirum

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2014
• First Posted: April 21, 2014
• Study Start: March 16, 2015
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: July 1, 2021
• Results First Posted: June 22, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (10)