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

NCT ID: NCT02787304

Last Updated: 2019-11-25

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

197 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-24

Study Completion Date

2018-07-27

Brief Summary

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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).

Detailed Description

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Conditions

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Non-Alcoholic Steatohepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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SHP626 5 Milligram (mg)

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

Group Type EXPERIMENTAL

SHP626

Intervention Type DRUG

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

SHP626 10 Milligram (mg)

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

Group Type EXPERIMENTAL

SHP626

Intervention Type DRUG

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

SHP626 20 Milligram (mg)

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

Group Type EXPERIMENTAL

SHP626

Intervention Type DRUG

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

Placebo (PBO)

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo

Interventions

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SHP626

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

Intervention Type DRUG

Placebo

Matching placebo

Intervention Type DRUG

Other Intervention Names

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Volixibat (SHP626)

Eligibility Criteria

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Inclusion Criteria

1. An understanding, ability, and willingness to fully comply with study procedures and restrictions.
2. Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative, as applicable) informed consent to participate in the study.
3. Age 18-80 years inclusive. This inclusion criterion will only be assessed at the first screening visit.
4. 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).
5. 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.
6. 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).

Exclusion Criteria

1. Presence of or history of cirrhosis or evidence of decompensated liver disease (example: ascites, variceal bleeding, etc.) or hepatocellular carcinoma.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Uncontrolled diabetes defined as HbA1c of \>=9.5% within 60 days prior to enrollment.
9. 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%.
10. 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).
11. Serum aspartate aminotransferase (AST) greater than (\>) 7 times upper limit of normal (ULN) at screening.
12. Serum alanine aminotransferase (ALT) \>7 times ULN at screening.
13. Elevated serum creatinine \>=2.0 milligram/deciliter (mg/dL).
14. International normalized ratio (INR) \>1.3
15. 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).
16. Platelet count \<130 × 10\^9/liter (L)
17. Medical history of impaired hemostasis or use of anticoagulant medication (use of antiplatelet medications, such as low-dose, that is 81 mg, aspirin \[ASA\] or clopidogrel \[Plavix\] will be allowed).
18. Uncontrolled thyroid disease.
19. Type 1 diabetes mellitus.
20. Known or suspected intolerance or hypersensitivity to the IP, closely-related compounds, or any of the stated ingredients.
21. Known history of alcohol or other substance abuse within the last year or at any time during the study based on investigator's discretion. Weekly alcohol intake greater than 21 grams/day for males and 14 grams/day for females on average or inability to reliably quantify alcohol consumption based on investigator's judgment.
22. Within 6 months of MRI and liver biopsy:

* Have used any IP.
* Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study.
23. Inability to safely obtain a liver biopsy.
24. Females who are pregnant, planning to become pregnant, or are breastfeeding, or males who are planning to father a child during study participation.
25. The anticipated need for a surgical procedure during the study that could interfere with the treatment.
26. Known positivity for human immunodeficiency virus (HIV) infection.
27. Cancer within 5 years of screening, except for basal or squamous cell carcinoma of the skin or in situ cervical carcinoma that has been treated with no evidence of recurrence.
28. History of noncompliance with medical regimens, unreliability, mental instability or incompetence that could compromise the validity of informed consent or lead to noncompliance with the study protocol.
29. Any other conditions or abnormalities which, in the opinion of the investigator, may compromise the safety of the subject, or interfere with the subject participating.
30. Subject is currently enrolled in this study at any study site (unless the subject is transferring to another qualified study site with prior sponsor approval).
31. Subjects who are employees at the unit of the investigational site that is conducting the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mirum Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Mirum

Locations

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Southern California Research Center

Coronado, California, United States

Site Status

Fresno Clinical Research Center

Fresno, California, United States

Site Status

Ceders-Sinai Medical Center

Los Angeles, California, United States

Site Status

California Liver Research Institute

Pasadena, California, United States

Site Status

Inland Empire Liver Foundation

Rialto, California, United States

Site Status

South Denver Gastroenterology, PC

Englewood, Colorado, United States

Site Status

Medstar Georgetown University Hospital

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

Site Status

George Washington (GW) Medical Faculty Associates

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

Site Status

Schiff Center for Liver Diseases

Miami, Florida, United States

Site Status

South Florida Center of Gastroenterology

Wellington, Florida, United States

Site Status

Internal Medicine Associates of Wellstar Atlanta Medical

Atlanta, Georgia, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States

Site Status

The Queen's Medical Center - Liver Center

Honolulu, Hawaii, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Liver Research Center

Louisville, Kentucky, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Louisiana Research Center, LLC

Shreveport, Louisiana, United States

Site Status

Mercy Medical Center

Baltimore, Maryland, United States

Site Status

Digestive Disease Associates

Catonsville, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Site Status

Henry Ford Health System

Novi, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Kansas City Research Institute

Kansas City, Missouri, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Northwell Health Inc.

Manhasset, New York, United States

Site Status

Concorde Medical Group PLLC

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Center for Liver Disease

Charlotte, North Carolina, United States

Site Status

DUMC-Gastroenterology

Durham, North Carolina, United States

Site Status

Cumberland Research Associates, LLC

Fayetteville, North Carolina, United States

Site Status

Carolinas Center for Liver Disease

Statesville, North Carolina, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Clinsearch, LLC

Chattanooga, Tennessee, United States

Site Status

University of TN Health Science Center

Memphis, Tennessee, United States

Site Status

Quality Medical Research

Nashville, Tennessee, United States

Site Status

Austin Center for Clinical Research

Austin, Texas, United States

Site Status

Methodist Health Systems Clinical

Dallas, Texas, United States

Site Status

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

DHAT Research Institute

Richardson, Texas, United States

Site Status

UVM Medical Center

Burlington, Vermont, United States

Site Status

Digestive and Liver Disease Specialists

Norfolk, Virginia, United States

Site Status

Bon Secours Liver Institute of Virginia

Richmond, Virginia, United States

Site Status

McGuire VA Medical Center

Richmond, Virginia, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

UW Digestive Health Center (DHC)

Madison, Wisconsin, United States

Site Status

University of Calgary Liver Unit

Calgary, Alberta, Canada

Site Status

LAIR Centre

Vancouver, British Columbia, Canada

Site Status

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, Canada

Site Status

Nova Scotia Heath Authority

Halifax, Nova Scotia, Canada

Site Status

Toronto Liver Centre

Toronto, Ontario, Canada

Site Status

CRCHUM

Montreal, Quebec, Canada

Site Status

UPR: Medical Sciences Campus

San Juan, , Puerto Rico

Site Status

Royal Free Hospital

Hampstead, London, United Kingdom

Site Status

Norfolk & Norwich University Hospital

Norwich, Norfolk, United Kingdom

Site Status

John Radcliffe Hospital

Oxford, Oxfordshire, United Kingdom

Site Status

NHS Tayside

Dundee, Tayside, United Kingdom

Site Status

University Hospital Birmingham

Birmingham, West Midlands, United Kingdom

Site Status

Royal London Hospital

London, , United Kingdom

Site Status

Nottingham Digestive Diseases Centre and Biomedical Research Unit

Nottingham, , United Kingdom

Site Status

Abertawe Bro Morgannwg University

Swansea, , United Kingdom

Site Status

York Clinical Research Facility

York, , United Kingdom

Site Status

Countries

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United States Canada Puerto Rico United Kingdom

References

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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.

Reference Type DERIVED
PMID: 32234329 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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2016-000203-82

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SHP626-201

Identifier Type: -

Identifier Source: org_study_id

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