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

Study Overview
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Brief Summary
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This is a two-part randomized study of volixibat in patients with Intrahepatic Cholestasis of Pregnancy (ICP) and elevated serum bile acid concentrations (sBA). Part 1 is an open-label study 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.

Official Title
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A Phase 2a/2b Randomized Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Volixibat in Adult Women With Intrahepatic Cholestasis of Pregnancy and Elevated Serum Bile Acid Concentrations (OHANA).

Conditions
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Intrahepatic Cholestasis of Pregnancy

Intervention / Treatment
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* Drug: Volixibat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Open-label two arm study (Part 1) followed by a randomized double-blind, placebo controlled, study (Part 2)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Arm 1 & Arm 2 - Volixibat 20mg/80mg<br>Part 1 Arm 1 - Volixibat 20mg (Experimental) Participants randomized to this arm will receive volixibat 20mg twice daily. Part 1 Arm 2 - Volixibat 80mg (Experimental) Participants randomized to this arm will receive volixibat 80mg twice daily. | Drug: Volixibat<br>* Oral capsules, administered twice daily. Volixibat is an ileal bile acid transporter (IBAT) inhibitor.<br>* Other names: SHP626;|
| Experimental: Part 2 Arm 1 - Volixibat Selected Dose mg<br>Part 2 Arm 1 - Volixibat Selected Dose mg (experimental) Participants randomized to this arm will receive volixibat selected dose (mg) twice daily. Part 2 Arm 2 - Placebo (Placebo Comparator) Participants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily. | Drug: Volixibat<br>* Oral capsules, administered twice daily. Volixibat is an ileal bile acid transporter (IBAT) inhibitor.<br>* Other names: SHP626;Drug: Placebo<br>* Capsules matched to study drug minus active substance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in serum bile acids | Part 1: To assess the safety and tolerability of volixibat in participants with ICP on the basis of the following endpoints Part 2: To assess the efficacy of volixibat on the reduction of elevated sBA concentrations in participants with ICP | 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 (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. | 
| Safety endpoint: The incidence of adverse events |  | Through to end of treatment, up to 25 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pruritus, Itch, Itching, Cholestasis, Bile Acid, Pregnancy, Pregnant, Intrahepatic, Liver, ICP