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Non-Alcoholic SteatohepatitisPhase 2NCT02787304

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

A Phase 2 study testing SHP626 in people with Non-Alcoholic Steatohepatitis, run by Mirum Pharmaceuticals, Inc. at 65 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Non-Alcoholic Steatohepatitis
What is being tested?
SHP626
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
197 participants
Where
65 sitesin 4 countries
Study dates
24 Oct 2016to 27 Jul 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Age 18-80 years inclusive. This inclusion criterion will only be assessed at the first screening visit.
  • 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).

Who cannot join

  • 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.
Show all 33Show fewer
  • 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).
  • Platelet count <130 × 10^9/liter (L)
  • 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).
  • Uncontrolled thyroid disease.
  • Type 1 diabetes mellitus.
  • Known or suspected intolerance or hypersensitivity to the IP, closely-related compounds, or any of the stated ingredients.
  • 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.
  • 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.
  • Inability to safely obtain a liver biopsy.
  • Females who are pregnant, planning to become pregnant, or are breastfeeding, or males who are planning to father a child during study participation.
  • The anticipated need for a surgical procedure during the study that could interfere with the treatment.
  • Known positivity for human immunodeficiency virus (HIV) infection.
  • 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.
  • 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.
  • 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.
  • 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).
  • Subjects who are employees at the unit of the investigational site that is conducting the study.

Trial locations and contacts

65 sites in 4 countries.

65 sites in 4 countries

United States49 sites

  • Internal Medicine Associates of Wellstar Atlanta Medical

    Atlanta, Georgia, 30312

  • Emory University

    Atlanta, Georgia, 30322

  • Austin Center for Clinical Research

    Austin, Texas, 78756

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • UVM Medical Center

    Burlington, Vermont, 05401

  • Digestive Disease Associates

    Catonsville, Maryland, 21228

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Center for Liver Disease

    Charlotte, North Carolina, 28204

  • Clinsearch, LLC

    Chattanooga, Tennessee, 37421

  • Southern California Research Center

    Coronado, California, 92118

  • Methodist Health Systems Clinical

    Dallas, Texas, 75203

  • DUMC-Gastroenterology

    Durham, North Carolina, 27710

  • South Denver Gastroenterology, PC

    Englewood, Colorado, 80113

  • Cumberland Research Associates, LLC

    Fayetteville, North Carolina, 28304

  • Fresno Clinical Research Center

    Fresno, California, 93720

  • The Queen's Medical Center - Liver Center

    Honolulu, Hawaii, 96813

  • Baylor College of Medicine - Advanced Liver Therapies

    Houston, Texas, 77030

  • Texas Children's Hospital

    Houston, Texas, 77030

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Kansas City Research Institute

    Kansas City, Missouri, 64157

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Ceders-Sinai Medical Center

    Los Angeles, California, 90048

  • Liver Research Center

    Louisville, Kentucky, 40202

  • UW Digestive Health Center (DHC)

    Madison, Wisconsin, 53792

  • Northwell Health Inc.

    Manhasset, New York, 11030

  • Gastrointestinal Specialists of Georgia

    Marietta, Georgia, 30060

  • University of TN Health Science Center

    Memphis, Tennessee, 038104

  • Schiff Center for Liver Diseases

    Miami, Florida, 33136

  • Quality Medical Research

    Nashville, Tennessee, 37211

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

  • Concorde Medical Group PLLC

    New York, New York, 10016

  • Digestive and Liver Disease Specialists

    Norfolk, Virginia, 23502

  • Henry Ford Health System

    Novi, Michigan, 48377

  • California Liver Research Institute

    Pasadena, California, 91105

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Inland Empire Liver Foundation

    Rialto, California, 92377

  • DHAT Research Institute

    Richardson, Texas, 75082

  • Bon Secours Liver Institute of Virginia

    Richmond, Virginia, 23226

  • McGuire VA Medical Center

    Richmond, Virginia, 23249

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • Louisiana Research Center, LLC

    Shreveport, Louisiana, 71105

  • Carolinas Center for Liver Disease

    Statesville, North Carolina, 28677

  • Medstar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • George Washington (GW) Medical Faculty Associates

    Washington D.C., District of Columbia, 20037

  • South Florida Center of Gastroenterology

    Wellington, Florida, 33414

  • University of Massachusetts Medical School

    Worcester, Massachusetts, 01605

Other trials in United States

United Kingdom9 sites

  • University Hospital Birmingham

    Birmingham, West Midlands, B15 2TH

  • NHS Tayside

    Dundee, Tayside, DD1 9SY

  • Royal Free Hospital

    Hampstead, London, NW3 2QG

  • Royal London Hospital

    London, E1 1BB

  • Norfolk & Norwich University Hospital

    Norwich, Norfolk, NR4 7UY

  • Nottingham Digestive Diseases Centre and Biomedical Research Unit

    Nottingham, NG7 2UH

  • John Radcliffe Hospital

    Oxford, Oxfordshire, OX3 9DU

  • Abertawe Bro Morgannwg University

    Swansea, SA2 8QA

  • York Clinical Research Facility

    York, YO31 8HE

Other trials in United Kingdom

Canada6 sites

  • University of Calgary Liver Unit

    Calgary, Alberta, T2N 4Z5

  • Nova Scotia Heath Authority

    Halifax, Nova Scotia, B3HJ 2Y9

  • CRCHUM

    Montreal, Quebec, H2X 0A9

  • Toronto Liver Centre

    Toronto, Ontario, M6H 3M1

  • LAIR Centre

    Vancouver, British Columbia, V5Z 1H2

  • Vancouver ID Research and Care Centre Society

    Vancouver, British Columbia, V6Z 2C7

Other trials in Canada

Puerto Rico1 site

  • UPR: Medical Sciences Campus

    San Juan, 00935

Other trials in Puerto Rico

About this study

Official title: A Phase 2 Double-blind, Randomized, Placebo-controlled, Dose-finding Study to Evaluate the Safety, Tolerability and Efficacy of Volixibat Potassium, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi) in Adults With Nonalcoholic Steatohepatitis (NASH)

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).

Being tested
SHP626, Placebo
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
Medical subject headings
Non-alcoholic Fatty Liver Disease, Liver Diseases, Fatty Liver

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SHP626Drug

    Also called Volixibat (SHP626)

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

  • PlaceboDrug

    Matching placebo

Study groups in NCT02787304
Study groupRoleWhat they receive
SHP626 5 Milligram (mg)ExperimentalSubject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
Receives: Drug: SHP626
SHP626 10 Milligram (mg)ExperimentalSubject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
Receives: Drug: SHP626
SHP626 20 Milligram (mg)ExperimentalSubject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
Receives: Drug: SHP626
Placebo (PBO)Placebo comparatorSubject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Baseline, Week 48

Secondary outcomes (9)

  1. Change From Baseline to Week 48 on Liver Histology

    Change in liver histology will be measured by the individual NAS components (ballooning, inflammation, steatosis). 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).

    Measured: Baseline, Week 48

  2. Change From Baseline to Week 48 on Hepatic Steatosis

    Change in hepatic steatosis will be evaluated by measuring the reduction of liver fat with magnetic resonance imaging-proton density fat-fraction (MRI-PDFF) and stratified by treatment group.

    Measured: Baseline, Week 48

  3. Change From Baseline to Week 48 on Liver Histology

    Change in liver histology will be measured by fibrosis stage. Fibrosis stage is assessed on a scale of 0-4 with higher scores indicating more severe disease and lower scores indicating less severe disease (F0 = no fibrosis, F4 = cirrhosis).

    Measured: Baseline, Week 48

  4. Number of Participants With Resolution of NASH at Week 48

    Resolution of NASH is defined as total absence of ballooning [score = 0], absent or mild inflammation [score 0-1], steatosis can be present [score 0-3]) without worsening of fibrosis as assessed by liver histology at Week 48.

    Measured: Week 48

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

    Serum liver-related biochemistry will be analysed by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT).

    Measured: Baseline, Week 48

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

    Serum liver-related biochemistry will be analysed by measuring total bilirubin (TB).

    Measured: Baseline, Week 48

  7. Change From Baseline to Week 48 on Metabolic Indicators

    Metabolic indicators will be assessed by measuring fasting serum glucose levels and insulin levels.

    Measured: Baseline, Week 48

  8. Change From Baseline to Week 48 on Metabolic Indicators

    Metabolic indicators will be assessed by measuring hemoglobin A1c (HbA1c).

    Measured: Baseline, Week 48

  9. Change From Baseline to Week 48 on Serum Lipids

    Serum lipids level will be measured by calculating fasting total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides.

    Measured: Baseline, Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2016 (estimated)
  2. Study start24 Oct 2016
  3. Primary completion27 Jul 2018
  4. Study completion27 Jul 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
197 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02787304
Sponsor's protocol ID
SHP626-201
Other IDs
2016-000203-82, 2016
Status last verified
Nov 2019
First submitted
11 May 2016
Last updated
25 Nov 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32234329

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SHP626 in people with Non-Alcoholic Steatohepatitis, run by Mirum Pharmaceuticals, Inc. at 65 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in United States, United Kingdom, Canada, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects Achieving Binary Response on Liver Histology Between Volixibat (SHP626) and Placebo at Week 48 (time frame: Baseline, Week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02787304, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2019.

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