Safety and Efficacy Study of LUM001 (Maralixibat) With a Drug Withdrawal Period in Participants With Alagille Syndrome (ALGS)

NCT02160782 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LUM001-3042013-005373-43
• Study Type: interventional
• Target: 31
• Locations: 6 countries
• Sites: 9

Brief Summary

This is a long-term, open-label study with a double-blind, placebo-controlled, randomized drug withdrawal period in children with Alagille Syndrome (ALGS) designed to evaluate the safety and efficacy of LUM001 (Also known as maralixibat or MRX).

Conditions

Alagille Syndrome

Outcome Measures

Primary Outcomes (1)

• Change From Week 18 to Week 22 in Fasting sBA Levels in Participants Who Had a Reduction in sBA ≥50% From Baseline to Week 12 or Week 18

  The primary efficacy endpoint of this study was the mean change from Week 18 to Week 22 (the RWD period) of fasting sBA levels in participants who had a reduction in sBA ≥50% from baseline to Week 12 or Week 18 (Modified Intent-to-Treat \[MITT\] Population). Five participants in the MRX group and 10 participants in the placebo group met the prespecified sBA reduction criteria.

  Week 18 to Week 22

Secondary Outcomes (13)

• Change From Baseline to Week 18 in Fasting sBA Levels

  Baseline to Week 18

• Change From Baseline to Week 18 in Pruritus as Measured by ItchRO (Obs)

  Baseline to Week 18

• Change From Baseline to Week 18 in Pruritus as Measured by ItchRO (Pt)

  Baseline to Week 18

• Change From Week 18 to Week 22 in Pruritus as Measured by ItchRO(Obs)

  Week 18 to Week 22

• Change From Week 18 to Week 22 in Pruritus as Measured by ItchRO(Pt)

  Week 18 to Week 22

Study Arms (2)

LUM001 (Maralixibat)

EXPERIMENTAL

LUM001, also known as Maralixibat (MRX) will be administered orally once a day (QD) up to 400 microgram per kilogram per day (mcg/kg/day) up to Week 52, followed by an increase in dose orally twice a day (BID) during long-term follow-up based on efficacy (serum bile acid \[sBA\] level and ItchRO\[Obs\] score) and safety assessment. Note: 400 mcg/kg maralixibat chloride is equivalent to 380 mcg/kg free maralixibat.

Drug: LUM001 (Maralixibat)

Placebo

PLACEBO COMPARATOR

Placebo will be administered orally once a day during randomized withdrawal period (Week 19 to Week 22)

Drug: Placebo

Interventions

LUM001 (Maralixibat) DRUG

LUM001, also known as Maralixibat (MRX) will be administered orally Once Daily (OD). To be administered Twice Daily (BID) for patients who are eligible.

LUM001 (Maralixibat)

Placebo DRUG

Placebo will be administered orally once daily during randomized withdrawal period

Placebo

Eligibility Criteria

• Age: 12 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female between the ages of 12 months and 18 years inclusive.
• Diagnosis of ALGS.
• Evidence of cholestasis (one or more of the following):
• Total serum bile acid \> 3x ULN for age.
• Conjugated bilirubin \> 1 mg/dL.
• Fat soluble vitamin deficiency otherwise unexplainable.
• GGT \> 3x ULN for age.
• Intractable pruritus explainable only by liver disease.
• Females of childbearing potential must have a negative serum pregnancy test during Screening.
• Males and females of child-bearing potential who are sexually active, or are not currently sexually active during the study, but become sexually active during the period of the study and 30 days following the last dose of study drug, must agree and use acceptable contraception during the trial.
• Participant is expected to have a consistent caregiver(s) for the duration of the study.
• Informed consent and assent (per IRB/IEC) as appropriate.
• Access to phone for scheduled calls from study site.
• Caregivers (and age-appropriate participants) must be willing and able to use an eDiary device during the study.
• Caregivers (and age-appropriate participants) must digitally accept the licensing agreement in the eDiary software.

You may not qualify if:

• Chronic diarrhea requiring ongoing intravenous fluid or nutritional intervention.
• Surgical interruption of the enterohepatic circulation.
• Previous liver transplant
• Decompensated cirrhosis (ALT \>15 x ULN, INR \>1.5 \[unresponsive to vitamin K therapy\], albumin \<3.0 g/dL, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy).
• History or presence of other concomitant liver disease.
• History or presence of any other disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs, including bile salt metabolism in the intestine (eg, inflammatory bowel disease).
• History or presence of gallstones or kidney stones.
• Known diagnosis of human immunodeficiency virus (HIV) infection.
• Cancers, except for in situ carcinoma, or cancers treated at least 5 years prior to Screening with no evidence of recurrence.
• Recent medical history or current status that suggests that the participant may be unable to complete the study.
• Any female who is pregnant or lactating or who is planning to become pregnant during the study period.
• Known history of alcohol or substance abuse.
• Administration of bile acid or lipid binding resins within 28 days prior to screening and throughout the trial.
• Known hypersensitivity to LUM001 or any of its components.
• Receipt of investigational drug, biologic, or medical device within 28 days prior to screening, or 5 half-lives of the study agent, whichever is longer.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (9)

Children's Hospital Westmead

Westmead, New South Wales, 2145, Australia

Location

The Royal Children's Hospital Melbourne

Parkville, Victoria, 3052, Australia

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Hopital Femme Mere Enfant De Lyon

Bron, 69677, France

Location

Hopital Necker-Enfants Malades

Paris, 75015, France

Location

Hopital Kremlin Bicetre

Paris, 94275, France

Location

The Children's Memorial Health Institute

Warsaw, 04-730, Poland

Location

Hospital Universitario La Paz- Hospital Materno Infantil

Madrid, 261, Spain

Location

Paediatric Liver Center, Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (2)

• Kamath BM, Goldstein A, Howard R, Garner W, Vig P, Marden JR, Billmyer E, Anderson A, Kirson N, Jacquemin E, Gonzales E. Maralixibat Treatment Response in Alagille Syndrome is Associated with Improved Health-Related Quality of Life. J Pediatr. 2023 Jan;252:68-75.e5. doi: 10.1016/j.jpeds.2022.09.001. Epub 2022 Sep 10.

  PMID: 36096175 DERIVED

• Gonzales E, Hardikar W, Stormon M, Baker A, Hierro L, Gliwicz D, Lacaille F, Lachaux A, Sturm E, Setchell KDR, Kennedy C, Dorenbaum A, Steinmetz J, Desai NK, Wardle AJ, Garner W, Vig P, Jaecklin T, Sokal EM, Jacquemin E. Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study. Lancet. 2021 Oct 30;398(10311):1581-1592. doi: 10.1016/S0140-6736(21)01256-3. Epub 2021 Oct 28.

  PMID: 34755627 DERIVED

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 analyzed or technical problems leading to unreliable data.

Results Point of Contact

• Title: Mirum Clinical Trials
• Organization: Mirum Pharmaceuticals

medinfo@mirumpharma.com

1 650-667-4085

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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Open-label single arm study with a randomized placebo-controlled parallel group period

Study Record Dates

• First Submitted: June 9, 2014
• First Posted: June 11, 2014
• Study Start: October 28, 2014
• Primary Completion: May 28, 2020
• Study Completion: May 28, 2020
• Last Updated: July 14, 2021
• Results First Posted: July 14, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); PL (1); AU (2); BE (1); FR (3); GB (1)