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A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (PSC)

Phase 2
Recruiting
Conditions
Primary Sclerosing Cholangitis
Interventions
Drug: Placebo
Registration Number
NCT04663308
Lead Sponsor
Mirum Pharmaceuticals, Inc.
Brief Summary

The purpose of this clinical research study is to learn more about the use of the study medicine, volixibat, for the treatment of pruritus (itching) associated with Primary Sclerosing Cholangitis (PSC), and to assess the possible impact on the disease progression of PSC.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
Inclusion Criteria
  1. Provide freely signed informed consent and assent (as applicable) and be willing to comply with all study visits and requirements through end of study, including the follow-up period.
  2. Subjects aged ≥12 years for eligible regions; otherwise ≥18 years
  3. Confirmed diagnosis of large duct or small duct PSC based on American Association for the Study of Liver Disease (AASLD) guidelines.
  4. Pruritus associated with PSC as assessed by Adult ItchRO.
  5. Ursodeoxycholic acid (UDCA) and anti-pruritic medication use will be allowed if meeting additional criteria.
  6. Concomitant Inflammatory Bowel Disease (IBD) is allowed if meeting additional criteria.
Exclusion Criteria
  1. Pruritus associated with an etiology other than PSC
  2. Evidence or clinical suspicion of decompensated cirrhosis, or a history of decompensation events
  3. History of ileostomy or small bowel surgery/resection or other surgeries that may have disrupted the enterohepatic circulation
  4. Evidence, history, or suspicion of other liver disease; PSC patients with AIH are not excluded.
  5. Bile duct stent or percutaneous bile duct drain placement, or balloon dilatation procedure of a stricture within 12 weeks of Screening
  6. Exceeding pre-defined biochemical values for alanine aminotransferase/aspartate aminotransferase (ALT/AST), estimated glomerular filtration rate (eGFR),serum creatinine (sCr), platelet count, international normalized ratio (INR) and total bilirubin
  7. History of liver transplantation

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part 1 Arm 1: Volixibat 20mgVolixibatParticipants randomized to this arm will receive volixibat 20mg twice daily.
Part 1 Arm 3: PlaceboPlaceboParticipants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily.
Part 2 Arm 2: PlaceboPlaceboParticipants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily.
Part 1 Arm 2: Volixibat 80mgVolixibatParticipants randomized to this arm will receive volixibat 80mg twice daily.
Part 2 Arm 1: Volixibat Selected Dose 20mgVolixibatParticipants randomized to this arm will receive volixibat 20mg twice daily.
Primary Outcome Measures
NameTimeMethod
Mean change in the daily itch scores using the Adult Itch Reported Outcome (Adult ItchRO) questionnaireBaseline through to Week 28

The Adult ItchRO is an 11-point NRS measurement of itch severity ranging from 0=no itch to 10=worst possible itch.

Secondary Outcome Measures
NameTimeMethod
The incidence of adverse eventsBaseline through to Week 28
Proportion of participants with itch response using the Adult ItchROBaseline through to Week 28
Changes in serum bile acid levelsBaseline through to Week 28
Changes in alkaline phosphataseBaseline through to Week 28
Changes in total bilirubin levelsBaseline through to Week 28
Change in Primary Sclerosing Cholangitis-Specific Patient-Reported OutcomeBaseline through to Week 28
Change in Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue questionnaireBaseline through to Week 28

The PROMIS® Fatigue questionnaire is a 5-point response scale. Respondents endorse each item using a 5-point response scale: Never, Rarely, Sometimes, Often, and Always.

Change in Patient-Reported Outcomes Measurement Information System (PROMIS®) sleep disturbance questionnaireBaseline through to Week 28

The PROMIS® Sleep Disturbance in an 8-item measure that assesses quality of sleep, sleep depth, and restoration associated with sleep. It is a 5-point response scale, the specific response options vary by items. The first 4 items use response options that range from Not at all to Very much. The next 3 items use response options that range from Never to Always. The final item assesses sleep quality ranging from Very poor to Very good.

Trial Locations

Locations (103)

McMaster University Hospital

🇨🇦

Hamilton, Ontario, Canada

Southern California Research Center

🇺🇸

Coronado, California, United States

Cedars Sinai Medical Center

🇺🇸

Los Angeles, California, United States

University of California, Davis

🇺🇸

Sacramento, California, United States

California Pacific Medical Center Research Institute

🇺🇸

San Francisco, California, United States

University of Colorado - Anschutz Medical Campus

🇺🇸

Aurora, Colorado, United States

MedStar Georgetown University Hospital

🇺🇸

Washington, District of Columbia, United States

Florida Research Institute

🇺🇸

Lakewood Ranch, Florida, United States

University of Miami - Schiff Center for Liver Diseases

🇺🇸

Miami, Florida, United States

Tampa General Hospital

🇺🇸

Tampa, Florida, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Southern Therapy and Advanced Research LLC

🇺🇸

Jackson, Mississippi, United States

Northwell Health

🇺🇸

Manhasset, New York, United States

New York University Langone Health

🇺🇸

New York, New York, United States

Weill Cornell Medical College

🇺🇸

New York, New York, United States

Columbia University Medical Center - Presbyterian Hospital and Vanderbilt Clinic

🇺🇸

New York, New York, United States

University of Rochester Medical Center - Strong Memorial Hospital

🇺🇸

Rochester, New York, United States

Duke Health - Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Science 37, Inc (Remote-homebased Telemedicine)

🇺🇸

Morrisville, North Carolina, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Einstein Healthcare Network - Einstein Medical Center

🇺🇸

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Galen Medical Group

🇺🇸

Hixson, Tennessee, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

The Liver Institute At Methodist Dallas Medical Center

🇺🇸

Dallas, Texas, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

Liver Associates of Texas

🇺🇸

Houston, Texas, United States

University of Utah Health Care

🇺🇸

Salt Lake City, Utah, United States

Bon Secours Liver Institution of Hampton Roads Mary Immaculate Hospital Office

🇺🇸

Newport News, Virginia, United States

Richmond Community Hospital LLC

🇺🇸

Richmond, Virginia, United States

University of Washington - Harborview Medical Center

🇺🇸

Seattle, Washington, United States

Liver Institute Northwest

🇺🇸

Seattle, Washington, United States

Hospital Italiano de Buenos Aires

🇦🇷

Buenos Aires, Argentina

Glenny Corp S.A.

🇦🇷

Ciudad Autónoma Buenos Aires, Argentina

Hospital El Cruce

🇦🇷

Florencio Varela, Argentina

Royal Adelaide Hospital

🇦🇺

Adelaide, Australia

Northern Health

🇦🇺

Epping, Australia

Liverpool Hospital

🇦🇺

Liverpool, Australia

Austin Health

🇦🇺

Melbourne, Australia

University of the Sunshine Coast

🇦🇺

Sippy Downs, Australia

Cliniques Universitaires Saint-Luc

🇧🇪

Brussels, Belgium

Universitair Ziekenhuis Antwerpen (UZA)

🇧🇪

Gent, Belgium

University Hospital Ghent

🇧🇪

Gent, Belgium

Hospital das Clinicas da UFMG

🇧🇷

Belo Horizonte, Brazil

Hospital Das Clínicas Da Ufg

🇧🇷

Goiânia, Brazil

Hospital de Clinicas de Porto Alegre

🇧🇷

Porto Alegre, Brazil

Escola Bahiana de Medicina e Saude Publica

🇧🇷

Salvador, Brazil

Hospital do Rim e Hipertensao

🇧🇷

São Paulo, Brazil

University of Alberta

🇨🇦

Edmonton, Alberta, Canada

The Ottawa Hospital - General Campus

🇨🇦

Ottawa, Ontario, Canada

University Health Network - Toronto General Hospital

🇨🇦

Toronto, Ontario, Canada

University of Calgary

🇨🇦

Calgary, Canada

London Health Sciences Centre University Hospital

🇨🇦

London, Canada

McGill University Health Centre - Royal Victoria Hospital

🇨🇦

Montréal, Canada

Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes)

🇫🇷

Grenoble, France

Centre Hospitalier Universitaire de Lille

🇫🇷

Lille Cedex, France

APHP-Hôpital Saint Antoine

🇫🇷

Paris Cedex 12, France

CHU Bordeaux - Haut Lévêque

🇫🇷

Pessac, France

Hannover Medical School

🇩🇪

Hannover, Lower Saxony, Germany

Universitaetsklinikum Bonn

🇩🇪

Bonn, Nordrhine-Westphalia, Germany

Charité Universtitätsmedizin - Campus Virchow-Klinikum

🇩🇪

Berlin, Germany

Universitaetsklinikum Erlangen

🇩🇪

Erlangen, Germany

Universitätsklinikum Schleswig-Holstein - Campus Kiel

🇩🇪

Kiel, Germany

Universitatsklinikum Leipzig

🇩🇪

Leipzig, Germany

Otto-von-Guericke-Universitat Magdeburg

🇩🇪

Magdeburg, Germany

University Hospital Tubingen Medical Clinic

🇩🇪

Tübingen, Germany

St. Josefs-Hospital Wiesbaden

🇩🇪

Wiesbaden, Germany

Hillel Yaffe Medical Center

🇮🇱

Hadera, Israel

Rambam Medical Center

🇮🇱

Haifa, Israel

Carmel Medical Center

🇮🇱

Haifa, Israel

Shaare Zedek Medical Center

🇮🇱

Jerusalem, Israel

Hadassah Medical Center - Ein Karem

🇮🇱

Jerusalem, Israel

Galilee Medical Center

🇮🇱

Nahariyya, Israel

Rabin Medical Center

🇮🇱

Petach Tikva, Israel

Sheba Medical Center

🇮🇱

Ramat Gan, Israel

Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S. Orsola-Malpighi

🇮🇹

Bologna, Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

🇮🇹

Milan, Italy

ASST Grande Ospedale Metropolitano Niguarda

🇮🇹

Milan, Italy

Fondazione IRCCS San Gerardo dei Tintori

🇮🇹

Monza, Italy

A.O.U. Federico II

🇮🇹

Napoli, Italy

Azienda Ospedale Universita Padova

🇮🇹

Padova, Italy

Amsterdam UMC - VU Medisch Centrum (VUmc)

🇳🇱

Amsterdam, Netherlands

Universitair Medisch Centrum Groningen

🇳🇱

Groningen, Netherlands

Radboud University Medical Centre (MC)

🇳🇱

Nijmegen, Netherlands

Erasmus University Medical Center

🇳🇱

Rotterdam, Netherlands

Hospital Clinic Barcelona

🇪🇸

Barcelona, Spain

Hospital General Universitario Gregorio Maranon

🇪🇸

Madrid, Spain

University Hospital Zurich

🇨🇭

Zürich, Switzerland

Royal Free Hospital

🇬🇧

London, Hampstead, United Kingdom

John Radcliffe Hospital

🇬🇧

Oxford, Headington, United Kingdom

Royal Victoria Hospital

🇬🇧

Belfast, United Kingdom

University Hospitals Birmingham NHS Foundation Trust - Wellcome Trust Birmingham Clinical Research Facility

🇬🇧

Birmingham, United Kingdom

Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital

🇬🇧

Cambridge, United Kingdom

Lothian NHS Board

🇬🇧

Edinburgh, United Kingdom

St James' University Hospital Leeds Teaching Hospitals NHS Trust

🇬🇧

Leeds, United Kingdom

King's College Hospital NHS Foundation Trust

🇬🇧

London, United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust - Royal Victoria Infirmary

🇬🇧

Newcastle Upon Tyne, United Kingdom

Nottingham University Hospital NHS Trust

🇬🇧

Nottingham, United Kingdom

University Hospital Southampton NHS Foundation Trust

🇬🇧

Southampton, United Kingdom

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