Volixibat (SHP626) in the Treatment of Adults With Nonalcoholic Steatohepatitis (NASH)

NCT02787304 | Terminated Phase 2 Results DMC

• 2 other identifiers: SHP626-2012016-000203-82
• Study Type: interventional
• Target: 197
• Locations: 4 countries
• Sites: 65

Brief Summary

The purpose of this study is to determine if the investigational treatment volixibat (SHP626) is safe, tolerable and effective in adults with nonalcoholic steatohepatitis (NASH).

Conditions

Non-Alcoholic Steatohepatitis

Keywords

NAFLD activity score; ASBTi; MRI PDFF; NAS; NAFLD; liver disease; ASBT; MRI proton density fat fraction; nonalcoholic steatohepatitis; apical sodium dependent bile acid transporter inhibitor; fatty liver; NASH

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Achieving Binary Response on Liver Histology Between Volixibat (SHP626) and Placebo at Week 48

  Binary response indicating (yes/no) whether a subject responded at week 48 with a reduction of at least 2 points, without worsening of fibrosis, from baseline nonalcoholic fatty liver disease (NAFLD) activity score (NAS). The NAS grades NAFLD on liver biopsy based on the individual scoring of steatosis, inflammation and ballooning. The NAS is assessed on a scale of 0 to 8 with higher scores indicating more severe disease and lower scores indicating less severe disease. NAS is obtained by adding steatosis(assessed on a scale of 0 to 3), inflammation (assessed on a scale of 0 to 3) and ballooning (assessed on a scale of 0 to 2).

  Baseline, Week 48

Secondary Outcomes (9)

• Change From Baseline to Week 48 on Liver Histology

  Baseline, Week 48

• Change From Baseline to Week 48 on Hepatic Steatosis

  Baseline, Week 48

• Change From Baseline to Week 48 on Liver Histology

  Baseline, Week 48

• Number of Participants With Resolution of NASH at Week 48

  Week 48

• Change From Baseline to Week 48 on Serum Liver-related Biochemistry

  Baseline, Week 48

Study Arms (4)

SHP626 5 Milligram (mg)

EXPERIMENTAL

Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion

Drug: SHP626

SHP626 10 Milligram (mg)

EXPERIMENTAL

Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion

Drug: SHP626

SHP626 20 Milligram (mg)

EXPERIMENTAL

Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion

Drug: SHP626

Placebo (PBO)

PLACEBO COMPARATOR

Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion

Drug: Placebo

Interventions

SHP626 DRUG

5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion

Also known as: Volixibat (SHP626)

SHP626 10 Milligram (mg); SHP626 20 Milligram (mg); SHP626 5 Milligram (mg)

Placebo DRUG

Matching placebo

Placebo (PBO)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An understanding, ability, and willingness to fully comply with study procedures and restrictions.
• Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative, as applicable) informed consent to participate in the study.
• Male, or non-pregnant, non-lactating female, who is sexually active and who agrees to comply with the contraceptive requirements of the protocol, or females of non-childbearing potential. Males and females of child-bearing potential who are sexually active must agree to use acceptable contraception during the study and for 30 days following the last dose of the investigational product (IP).
• Presence of greater than equals to (\>=) 5 percent (%) steatosis on screening magnetic resonance imaging (MRI) from a centrally read radiologist performed either during the screening period or within 6 months prior to the first visit.
• Histologic confirmation of nonalcoholic steatohepatitis (NASH) without cirrhosis (F0-F3) from a centrally read liver biopsy performed either during the screening period or within 6 months prior to the first visit with a NAS of \>=4 with a score of at least 1 in each component (steatosis, lobular inflammation, and hepatocyte ballooning).

You may not qualify if:

• Presence of or history of cirrhosis or evidence of decompensated liver disease (example: ascites, variceal bleeding, etc.) or hepatocellular carcinoma.
• History or presence of other concomitant liver disease as assessed by the investigator or determined by laboratory findings including, but not limited to: active hepatitis B virus (HBV) infection (hepatitis B surface antigen \[HBsAg\] positive and/or hepatitis B virus deoxyribonucleic acid (HBVDNA) positive; subjects who are hepatitis B core antibody \[HBcAb\] positive may be eligible as long as HBsAg is negative and HBVDNA is non detectable), active hepatitis C virus (HCV) infection (prior exposure to HCV \[defined as HCVAb positive\] without a current or prior history of a detectable HCVRNA) may be eligible, alcoholic liver disease, proven autoimmune hepatitis, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, bile duct obstruction, liver primary or metastatic cancer.
• Current or recurrent disease that could affect the action, absorption, disposition, or laboratory assessment of the IP (including bile salt metabolism in the intestine) example (e.g,) uncontrolled inflammatory bowel disease, uncontrolled celiac disease, gastric bypass procedures (gastric lap band or gastric sleeve is acceptable), ileal or ileocecal resection, uncontrolled irritable bowel syndrome with predominant diarrhea, or history of chronic diarrhea or loose stools of any etiology.
• Weight change \>=5% after qualifying liver biopsy and/or MRI performed. If the subject had a liver biopsy and/or MRI within 6 months of screening, but experienced a weight change of \>=5% since the date of liver biopsy and/or MRI, the liver biopsy and/or MRI must be repeated at screening.
• Contraindications to MRI (e.g, claustrophobia, coronary stents, coronary implantable devices, girth, etc.). Stents or other devices may be allowed, at the investigator's discretion, if they do not interfere with the functioning of the MRI machine.
• Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to complete the study.
• Treatment with Vitamin E, thiazolidinediones (TZD), or glucagon-like peptide-1 receptor agonists (GLP-1 RA) unless subject on a stable dose for 6 months prior to qualifying liver biopsy and not initiated after qualifying liver biopsy and will continue the same dosing regimen throughout study participation.
• Uncontrolled diabetes defined as HbA1c of \>=9.5% within 60 days prior to enrollment.
• Current use of any medication (including over-the-counter, herbal, or homeopathic preparations) that could affect the action, absorption, or disposition of the IP, or clinical or laboratory assessment. (Current use is defined as use within 14 days of screening). Subjects currently taking insulin will not be excluded; however, they must be on a stable dose for at least 30 days prior to screening, or a sliding scale of insulin is allowed as long as the subject's HbA1c remains less than (\<) 9.5%.
• Use of drugs, herbs or supplements historically associated with causing or worsening NAFLD/NASH for less than 6 months prior to liver biopsy, or initiated any time after liver biopsy performed, including the use of total parenteral nutrition (TPN).
• Serum aspartate aminotransferase (AST) greater than (\>) 7 times upper limit of normal (ULN) at screening.
• Serum alanine aminotransferase (ALT) \>7 times ULN at screening.
• Elevated serum creatinine \>=2.0 milligram/deciliter (mg/dL).
• International normalized ratio (INR) \>1.3
• Total bilirubin (TB) \>2.0 times ULN at screening (Except for documented Gilbert's syndrome with bilirubin levels 20 micromole per liter (mcmol/L) to 90 mcmol/L (1.2 to 5.3 mg/dL) and with a ratio of unconjugated/conjugated bilirubin that is commensurately higher).

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (65)

Southern California Research Center

Coronado, California, 92118, United States

Location

Fresno Clinical Research Center

Fresno, California, 93720, United States

Location

Ceders-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Inland Empire Liver Foundation

Rialto, California, 92377, United States

Location

South Denver Gastroenterology, PC

Englewood, Colorado, 80113, United States

Location

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

George Washington (GW) Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

Schiff Center for Liver Diseases

Miami, Florida, 33136, United States

Location

South Florida Center of Gastroenterology

Wellington, Florida, 33414, United States

Location

Internal Medicine Associates of Wellstar Atlanta Medical

Atlanta, Georgia, 30312, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Gastrointestinal Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

The Queen's Medical Center - Liver Center

Honolulu, Hawaii, 96813, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Liver Research Center

Louisville, Kentucky, 40202, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Louisiana Research Center, LLC

Shreveport, Louisiana, 71105, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Digestive Disease Associates

Catonsville, Maryland, 21228, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01605, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64157, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Northwell Health Inc.

Manhasset, New York, 11030, United States

Location

Concorde Medical Group PLLC

New York, New York, 10016, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Center for Liver Disease

Charlotte, North Carolina, 28204, United States

Location

DUMC-Gastroenterology

Durham, North Carolina, 27710, United States

Location

Cumberland Research Associates, LLC

Fayetteville, North Carolina, 28304, United States

Location

Carolinas Center for Liver Disease

Statesville, North Carolina, 28677, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Clinsearch, LLC

Chattanooga, Tennessee, 37421, United States

Location

University of TN Health Science Center

Memphis, Tennessee, 038104, United States

Location

Quality Medical Research

Nashville, Tennessee, 37211, United States

Location

Austin Center for Clinical Research

Austin, Texas, 78756, United States

Location

Methodist Health Systems Clinical

Dallas, Texas, 75203, United States

Location

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

DHAT Research Institute

Richardson, Texas, 75082, United States

Location

UVM Medical Center

Burlington, Vermont, 05401, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, 23502, United States

Location

Bon Secours Liver Institute of Virginia

Richmond, Virginia, 23226, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

UW Digestive Health Center (DHC)

Madison, Wisconsin, 53792, United States

Location

University of Calgary Liver Unit

Calgary, Alberta, T2N 4Z5, Canada

Location

LAIR Centre

Vancouver, British Columbia, V5Z 1H2, Canada

Location

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Nova Scotia Heath Authority

Halifax, Nova Scotia, B3HJ 2Y9, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

CRCHUM

Montreal, Quebec, H2X 0A9, Canada

Location

UPR: Medical Sciences Campus

San Juan, 00935, Puerto Rico

Location

Royal Free Hospital

Hampstead, London, NW3 2QG, United Kingdom

Location

Norfolk & Norwich University Hospital

Norwich, Norfolk, NR4 7UY, United Kingdom

Location

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

NHS Tayside

Dundee, Tayside, DD1 9SY, United Kingdom

Location

University Hospital Birmingham

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

Royal London Hospital

London, E1 1BB, United Kingdom

Location

Nottingham Digestive Diseases Centre and Biomedical Research Unit

Nottingham, NG7 2UH, United Kingdom

Location

Abertawe Bro Morgannwg University

Swansea, SA2 8QA, United Kingdom

Location

York Clinical Research Facility

York, YO31 8HE, United Kingdom

Location

Related Publications (1)

• Newsome PN, Palmer M, Freilich B, Sheikh MY, Sheikh A, Sarles H, Herring R, Mantry P, Kayali Z, Hassanein T, Lee HM, Aithal GP; Volixibat in Adults study group. Volixibat in adults with non-alcoholic steatohepatitis: 24-week interim analysis from a randomized, phase II study. J Hepatol. 2020 Aug;73(2):231-240. doi: 10.1016/j.jhep.2020.03.024. Epub 2020 Mar 29.

  PMID: 32234329 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Diseases; Fatty Liver

Interventions

volixibat

Condition Hierarchy (Ancestors)

Digestive System Diseases

Limitations and Caveats

At the Week 24 Interim Analysis, no differences were observed between any dose of Volixibat and placebo based on absolute change in steatosis from baseline, as assessed by MRI hepatic PDFF, and % change from baseline in ALT; the study was terminated.

Results Point of Contact

• Title: Study Physician
• Organization: Mirum

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: June 1, 2016
• Study Start: October 24, 2016
• Primary Completion: July 27, 2018
• Study Completion: July 27, 2018
• Last Updated: November 25, 2019
• Results First Posted: November 25, 2019

Record last verified: 2019-11

Locations

PR (1); GB (9); CA (6); US (49)