Maralixibat for Intrahepatic Cholestasis of Pregnancy (METAPHOR)

Maralixibat for the trEatment of inTrAhePatic cHOlestasis of pRegnancy (METAPHOR)

An open label phase 2a/b trial of maralixibat in patients with Intrahepatic Cholestasis of Pregnancy (ICP) and elevated serum bile acid concentrations (sBA) to evaluate safety and tolerability

Study Overview

• Status: Not yet recruiting
• Conditions: Intrahepatic Cholestasis of Pregnancy
• Intervention / Treatment: Drug: Maralixibat

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jenny Chambers; Phone Number: 07843 660349; Email: jenny.chambers@imperial.ac.uk

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2TG
    • Birmingham Womens and Childrens NHS Foundation Trust
  • London, United Kingdom, SE 1 7EH
    • Guy's and St Thomas' NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provide signed informed consent and be willing to comply with all study visits and requirements through end of study, including the follow-up period
2. Female aged ≥18 and ≤50 years with a viable singleton pregnancy between 20 weeks 0 days and 34 weeks 0 days (inclusive) at the screening visit, and no more than 35 weeks 0 days (inclusive) at the baseline visit.
3. Diagnosis of ICP
4. Non fasting (e.g., postprandial) tSBA level ≥19 μmol/L as assessed by the local laboratory.
5. Meets all inclusion criteria and no exclusion criteria at screening as well as at the Day 1 (baseline) visit, unless otherwise specified.

Exclusion Criteria:

1. At the time of either the screening or baseline visit, decision has already been made to deliver within the next 7 days, for any indication.
2. Known non-reassuring fetal status based upon antepartum testing (e.g., NST/CTG) at or within 7 days before the baseline visit.
3. Known fetal anomaly likely to result in intrauterine fetal demise or neonatal death within the first 30 days of life.
4. Participating in another ongoing interventional clinical study at screening or planning to participate in another contemporaneous interventional clinical study while participating in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maralixibat; Dose-titrated open-label maralixibat, with primary assessment at Week 3; participants may continue treatment until delivery	Drug: Maralixibat; Oral solution, dose-titrated. Maralixibat is an ileal bile acid transporter (IBAT) inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the Safety and Tolerability of Maralixibat in Participants With ICP	To assess the safety and tolerability of maralixibat in participants with ICP on the basis of the following endpoints: Proportion of participants experiencing one or more of the following: To assess the safety and tolerability of maralixibat for the treatment of intrahepatic cholestasis of pregnancy (ICP) in pregnant women. Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs that lead to discontinuation Incidence of clinically relevant laboratory abnormalities .	Through to end of treatment, up to 21 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in the Weekly Average Worst Daily Itch Score as Measured by the Adult Itch Reported Outcome (5-D Itch Scale)	Mean change from baseline to Week 3 (minimum 7 days) of the study treatment period in the weekly average worst daily itch score as measured by the Adult Itch Reported Outcome (5-D Itch Scale)	Through the end of treatment (up to 21 weeks).
Mean Change in Total Serum Bile Acid (tSBA) Concentration	Mean change from baseline to Week 3 of the study treatment period in total tSBA concentration (minimum 7 days).	Baseline to Week 3 (minimum 7 days of treatment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with a Composite Adverse Perinatal Outcome	Number of adverse outcomes recorded from baseline to birth visit/end of study	Up to 28 days after delivery

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Mirum Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Catherine Williamson, MD, Imperial College London

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: January 26, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 5, 2026

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Pregnancy; Itch; Pruritus; Liver; Cholestasis; Itching; Pregnant; Bile Acid; Intrahepatic
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Manifestations; Biliary Tract Diseases; Skin Diseases; Bile Duct Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Cholestasis; Pruritus; Intrahepatic Cholestasis of Pregnancy; maralixibat
• Other Study ID Numbers: 1012589; X (Mirum Pharmaceuticals, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes