A Placebo-controlled Study of Volixibat in Subjects With Elevated Serum Bile Acids Associated With Intrahepatic Cholestasis of Pregnancy (OHANA)

NCT04718961 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: VLX-4012020-003448-96
• Study Type: interventional
• Target: 4
• Locations: 3 countries
• Sites: 20

Brief Summary

Part 1 is an open-label randomized study of volixibat in patients with Intrahepatic Cholestasis of Pregnancy (ICP) and elevated serum bile acid concentrations (sBA) to evaluate safety and tolerability of two doses of volixibat. Part 2 is a double-blind, placebo controlled, study designed to evaluate the safety and efficacy of a selected volixibat dose.

Conditions

Intrahepatic Cholestasis of Pregnancy

Keywords

Pruritus; Itch; Itching; Cholestasis; Bile Acid; Pregnancy; Pregnant; Intrahepatic; Liver; ICP

Outcome Measures

Primary Outcomes (1)

• Assess the Safety and Tolerability of Volixibat in Participants With ICP

  To assess the safety and tolerability of volixibat in participants with ICP on the basis of the following endpoints: Proportion of participants experiencing one or more of the following: Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), events of clinical interest (ECIs), and adverse events (AEs) that lead to discontinuation of study drugs. Clinically significant laboratory abnormalities

  Through to end of treatment, up to 21 weeks

Secondary Outcomes (2)

• Mean Change in the Weekly Average Worst Daily Itch Score as Measured by the Adult Itch Reported Outcome (ItchRO)

  Through to end of treatment, up to 21 weeks

• Proportion of Participants Experiencing One or More of Adverse Perinatal Outcomes

  At least one month after delivery.

Study Arms (4)

Part 1 Arm 1 - Volixibat 20mg

EXPERIMENTAL

Participants randomized to this arm will receive volixibat 20mg twice daily.

Drug: Volixibat

Part 1 Arm 2 - Volixibat 80mg

EXPERIMENTAL

Participants randomized to this arm will receive volixibat 80mg twice daily.

Drug: Volixibat

Part 2 Arm 1 - Volixibat Selected Dose mg

EXPERIMENTAL

Participants randomized to this arm will receive volixibat selected dose (mg) twice daily.

Drug: Volixibat

Part 2 Arm 2 - Placebo (Placebo Comparator)

PLACEBO COMPARATOR

Participants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily.

Drug: Placebo

Interventions

Volixibat DRUG

Oral capsules, administered twice daily. Volixibat is an ileal bile acid transporter (IBAT) inhibitor.

Also known as: SHP626

Part 1 Arm 1 - Volixibat 20mg; Part 1 Arm 2 - Volixibat 80mg; Part 2 Arm 1 - Volixibat Selected Dose mg

Placebo DRUG

Capsules matched to study drug minus active substance.

Part 2 Arm 2 - Placebo (Placebo Comparator)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female aged ≥18 and ≤45 years with a viable pregnancy.
• Provide signed informed consent as described in the protocol and willing to comply with all study visits and requirements.
• Diagnosis of ICP.
• (Part 2 only) Qualified level of pruritus associated with ICP, during screening.

You may not qualify if:

• 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.
• Known non-reassuring fetal status based upon antepartum testing (e.g., NST/CTG or BPP) at or within 7 days before the baseline visit.
• Known fetal anomaly likely to result in intrauterine fetal demise or neonatal death within the first 30 days of life.
• Participating in another ongoing interventional clinical study at screening or planning to participate in another contemporaneous interventional clinical study while participating in this study.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06511, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

The University of Texas Medical Branch - Galveston

Galveston, Texas, 77555, United States

Location

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Dunedin Hospital

Dunedin, Otago, 6021, New Zealand

Location

Christchurch Women's Hospital

Christchurch, 8011, New Zealand

Location

Capital & Coast District Health Board, Wellington Regional Hospital

Wellington, 6021, New Zealand

Location

Medway NHS Foundation Trust

Gillingham, Kent, ME7 5NY, United Kingdom

Location

Bradford Royal Infirmary

Bradford, West Yorkshire, BD9 6RJ, United Kingdom

Location

Birmingham Womens and Childrens NHS Foundation Trust

Birmingham, B15 2TG, United Kingdom

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

St Richard's Hospital

Chichester, PO19 6SE, United Kingdom

Location

Barts Health NHS Trust- Whipps Cross University Hospital

London, E11 1NR, United Kingdom

Location

Royal Free London Hospital NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE 1 7EH, United Kingdom

Location

West Middlesex University Hospital

Middlesex, TW7 6AF, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, United Kingdom

Location

Related Publications (1)

• Ovadia C, Stone S, Sibai B, Nunes T, Mogul DB, Krishnaswami J, Kahng J, Li F, Warsi QA, Chien E, Vig P, Williamson C. Efficacy, Safety and Tolerability of Volixibat, an IBAT Inhibitor, in Patients With Intrahepatic Cholestasis of Pregnancy. Liver Int. 2026 Mar;46(3):e70523. doi: 10.1111/liv.70523.

  PMID: 41603551 DERIVED

MeSH Terms

Conditions

Intrahepatic Cholestasis of Pregnancy; Pruritus; Cholestasis

Interventions

volixibat

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Results Point of Contact

• Title: Mirum Clinical Trials
• Organization: Mirum Pharmaceuticals

medinfo@mirumpharma.com

650-667-4085

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Masking in Part 2 Only
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized Open-label two arm study (Part 1) followed by a randomized double-blind, placebo controlled, study (Part 2)

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 22, 2021
• Study Start: January 4, 2021
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022
• Last Updated: August 6, 2024
• Results First Posted: August 6, 2024

Record last verified: 2024-07

Locations

US (7); NZ (3); GB (10)