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Liver Fibrosis Due to NASHPhase 2NASHNCT01672879

Simtuzumab (SIM, GS-6624) in the Treatment of Cirrhosis Due to NASH

A Phase 2 study testing SIM in people with Liver Fibrosis Due to NASH, run by Gilead Sciences at 59 sites in 8 countries.

Terminated

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

Official record
Search all trials

Trial summary

The primary objective of this study is to evaluate the safety and efficacy of SIM (formerly referred to as GS-6624) in adults with compensated cirrhosis due to Non-Alcoholic Steatohepatitis (NASH). It will consist of 2 phases: Randomized Double-Blind Phase Open-Label Phase (optional) Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Liver Fibrosis Due to NASH
What is being tested?
SIM
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
259 participants
Where
59 sitesin 8 countries
Study dates
29 Oct 2012to 3 Jan 2017
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults with cirrhosis of the liver defined as an Ishak fibrosis stage ≥ 5
  • Liver biopsy consistent with NASH or cryptogenic cirrhosis
  • Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
  • The liver biopsy sample must be determined to be adequate for evaluation by the Central pathologist
  • Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x the upper limit of the normal range (ULN)
  • Must have serum creatinine < 2.0 mg/dL
Show all 10Show fewer
  • A negative serum pregnancy test is required for female subjects of childbearing potential
  • All sexually active female subjects of childbearing potential must agree to use a protocol recommended method of contraception during heterosexual intercourse throughout the study and for 90 days following the last dose of study medication
  • Lactating females must agree to discontinue nursing before starting study treatment
  • Male subjects, if not vasectomized, are required to use barrier contraception (condom plus spermicide) during heterosexual intercourse from the screening through the study completion and for 90 days following the last dose of study drug

Who cannot join

  • Pregnant or breast feeding
  • Any history of hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding
  • Weight reduction surgery in the past 5 year
  • Child-Pugh-Turcotte (CPT) score >7; Model for End-Stage Liver Disease (MELD) score > 12 and Body Mass Index (BMI) <18kg/m2
  • Positive for hepatitis C virus (HCV) RNA
  • Positive for HBsAg
Show all 17Show fewer
  • Alcohol consumption greater than 21oz/week for males or 14oz/week for females
  • Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at screening. Subjects on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to screening may be included in the study. Subjects with a positive urine drug screen due to prescription opioid-based medication are eligible if the prescription and diagnosis are reviewed and approved by the investigator
  • Clinically significant cardiac disease
  • History of malignancy, other than non-melanomatous skin cancer, within 5 years prior to screening
  • Major surgical procedure within 30 days prior to screening or the presence of an open wound
  • Known hypersensitivity to the investigation product or any of its formulation excipients
  • History of bleeding diathesis within 6 months of screening
  • Unavailable for follow-up assessment or concern for subject's compliance with the protocol procedures;
  • Participation in an investigational trial of a drug or device within 30 days prior to screening
  • History of solid-organ transplant; poor venous access or requirement for permanent or semi-permanent central vein catheter such as portacath
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

59 sites in 8 countries.

59 sites in 8 countries

United States41 sites

  • Texas Clinical Research Institute

    Arlington, Texas, 76012

  • University of Colorado, Denver

    Aurora, Colorado, 80045

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889

  • State University Of New York at Buffalo

    Buffalo, New York, 14203

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Health Center

    Charlottesville, Virginia, 22908

  • Northwestern University

    Chicago, Illinois, 60611

  • University Hospitals Case Medical Center

    Cleveland, Ohio, 44106

  • Iowa Digestive Disease Center

    Clive, Iowa, 50325

  • Southern California Liver Centers

    Coronado, California, 92118

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Brooke Army Medical Center

    Fort Sam Houston, Texas, 78234

  • St. Luke Episcopal Hospital

    Houston, Texas, 77030

  • Indiana University School of Medicine, Division of Gastroenterology/Hepatology

    Indianapolis, Indiana, 46202

  • University of Mississippi Medical Center

    Jackson, Michigan, 39216

  • University of Louisville

    Louisville, Kentucky, 40202

  • North Shore University Health System

    Manhasset, New York, 11030

  • Methodist University Hospital

    Memphis, Tennessee, 38104

  • University of Miami

    Miami, Florida, 33136

  • Intermountain Transplant Center

    Murray, Utah, 84107

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

  • Tulane University

    New Orleans, Louisiana, 70112

  • New York University

    New York, New York, 10016

  • Columbia University Medical Center

    New York, New York, 10032

  • Liver Institute of Virginia

    Newport News, Virginia, 23602

  • Digestive and Liver Disease Specialists

    Norfolk, Virginia, 23502

  • University of Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • University Gastroenterology

    Providence, Rhode Island, 02905

  • Bucheon St. Marys Hospital

    Richmond, Virginia, 23226

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Minnnesota Gastroenterology, PA

    Saint Paul, Minnesota, 55114

  • Alamo Clinical Research Associates

    San Antonio, Texas, 78215

  • University of California, San Diego (UCSD)

    San Diego, California, 92103

  • University of California San Francisco (UCSF)

    San Francisco, California, 94143

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • University of Washington

    Seattle, Washington, 98104

  • Saint Louis University Hospital

    St Louis, Missouri, 63110

  • Tampa General Hospital

    Tampa, Florida, 33606

Other trials in United States

France4 sites

  • Hôpital de la Croix Rousse

    Lyon, 69317

  • Hospital Saint-Antoine

    Paris, 75012

  • CHU Pitié-Salpêtrière

    Paris, 75013

  • Fonds de Recherche Honoraires

    Strasbourg, 67091

Other trials in France

Canada3 sites

  • Dalhousie University

    Halifax, Nova Scotia, B3H 2Y9

  • Toronto Liver Centre

    Toronto, Ontario, M6H 3M1

  • University of Manitoba

    Winnipeg, Manitoba, R3E 3P4

Other trials in Canada

Italy3 sites

  • Azienda Ospedaliero-Universitaria Policlinico di Modena

    Modena, 41100

  • Istituto Clinico Humanitas

    Rozzano, Milano, 20089

  • Azienda Ospedaliera Città della Salute e della Scienza di Torino

    Torino, 10126

Other trials in Italy

United Kingdom3 sites

  • Royal Free Hospital, Pond Street

    London, NW3 2QG

  • King's College Hospital NHS Trust

    London, SE5 9RS

  • Nottingham University Hospitals Queen's Medical Centre

    Nottingham, NG7 2UH

Other trials in United Kingdom

Germany2 sites

  • Gastroenterologisch-Hepatologisches Zentrum Kiel

    Kiel, 24146

  • Eugastro Gmbh

    Leipzig, 4129

Other trials in Germany

Spain2 sites

  • Hospital Vall D´Hebron

    Barcelona, Catalonia, 08035

  • Hospital Universitario Puerta de Hierro

    Majadahonda, Madrid, 28222

Other trials in Spain

Puerto Rico1 site

  • Fundacion De Investigacion

    San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: A Phase 2b, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of GS-6624, a Monoclonal Antibody Against Lysyl Oxidase-Like 2 (LOXL2), in Subjects With Compensated Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

The primary objective of this study is to evaluate the safety and efficacy of SIM (formerly referred to as GS-6624) in adults with compensated cirrhosis due to Non-Alcoholic Steatohepatitis (NASH). It will consist of 2 phases:

  • Randomized Double-Blind Phase
  • Open-Label Phase (optional)
Being tested
Placebo, SIM
Keywords
NASH, cirrhosis, Compensated Liver disease, Monoclonal antibody, LOXL2, Simtuzumab, Nonalcoholic Steatohepatitis, Hepatic venous pressure gradient, HVPG, NAFLD, MRE, Liver biopsy, Liver fibrosis, Ishak
Medical subject headings
Fibrosis, Non-alcoholic Fatty Liver Disease, Liver Cirrhosis

What participants receive

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

  • PlaceboBiological

    Placebo to match SIM intravenous infusion over 30 minutes every 2 weeks

  • SIMBiological

    Also called GS-6624

    Intravenous infusion over 30 minutes every 2 weeks

Study groups in NCT01672879
Study groupRoleWhat they receive
SIM 200 mgExperimentalDuring the Randomized Double-Blind Phase, participants will receive SIM 200 mg via intravenous infusion every 2 weeks for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 700 mg via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Receives: Biological: SIM
SIM 700 mgExperimentalDuring the Randomized Double-Blind Phase, participants will receive SIM 700 mg via intravenous infusion every 2 weeks for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 700 mg via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Receives: Biological: SIM
PlaceboPlacebo comparatorDuring the Randomized Double-Blind Phase, participants will receive placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Receives: Biological: Placebo; Biological: SIM

What is being measured

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

  1. Change From Baseline in Hepatic Venous Pressure Gradient (HVPG)

    Measured: Baseline to Week 96

  2. Event-Free Survival (EFS) Using Kaplan-Meier

    Event free survival (EFS) was the primary clinical efficacy endpoint and was assessed by time to first liver-related event or death, whichever occurs first. Liver-related events included any of the following:

    • Liver transplantation
    • Qualification for liver transplantation
    • Model for End-Stage Liver Disease (MELD) ≥ 15
    • Events indicative of hepatic decompensation
    • Esophageal variceal bleeding
    • Ascites
    • Hepatic Encephalopathy
    • ≥ 2 point increase in Child Pugh-Turcotte (CPT) score
    • Newly diagnosed varices in a subject without prior varices

    Measured: Baseline up to the time of clinical event or last dose date (maximum: 240 weeks in Blinded Phase); which ever occurred first

Timeline

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

  1. First posted27 Aug 2012 (estimated)
  2. Study start29 Oct 2012
  3. Primary completion26 Sep 2016
  4. Study completion3 Jan 2017

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
259 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01672879
Sponsor's protocol ID
GS-US-321-0106
Other IDs
2012-002489-11
Acronym
NASH
Status last verified
Mar 2019
First submitted
22 Aug 2012
Last updated
27 Mar 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Sanyal A, Harrison S, Ratziu V, Abdelmalek M, Diehl A, Caldwell S, et al. Changes in fibrosis, but not the NAFLD Activity Score (NAS), are associated with disease progression in patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis. J Hepatol 2017; 66 (1): S2.

  • Sanyal A, Abdelmalek M, Diehl A, Caldwell S, Shiffman M, Ghalib R, et al. Efficacy and safety of simtuzumab for the treatment of nonalcoholic steatohepatitis with bridging fibrosis or cirrhosis: results of two phase 2b, dose-ranging, randomized, placebo-controlled trials. J Hepatol 2017; 66 (1): S54.

  • Bosch J, Harrison S, Ratziu V, Shiffman M, Diehl A, Caldwell S, et al. Impact of modest weight reduction on liver histology, portal pressure, and clinical events in patients with compensated cirrhosis due to nonalcoholic steatohepatitis. J Hepatol 2017; 66 (1): S159-S160.

  • Sanyal A, Goodman Z, Harrison S, Rockey DC, Diehl AM, Caldwell S, et al. Correlation between the hepatic venous pressure gradient and alpha-smooth muscle actin (SMA) expression in patients with compensated cirrhosis due to nonalcoholic steatohepatitis. J Hepatol 2016; 64 (2): S251.

  • Shea PR, Sanyal A, Harrison S, Ratziu V, Loomba R, Caldwell S, et al. PNPLA3 variants confer an increased risk of advanced fibrosis due to non-alcoholic steatohepatitis. J Hepatol 2016; 64 (2): S493.

  • Shea PR, Sanyal A, Rockey DC, Loomba R, Diehl AM, Kleinstein SE, et al. Genome-wide association study of clinically significant portal hypertension in patients with nonalcoholic steatohepatitis and advanced fibrosis. J Hepatol 2016; 64 (2): S280.

  • Bosch J, Ratziu V, Rockey DC, Ghalib RH, Thuluvath PJ, Shiefke I, et al. Correlation between noninvasive markers of fibrosis and the hepatic venous pressure gradient (HVPG) in patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH). Hepatol 2015; 62 (1): 578A.

  • Goodman ZD, Alaparthi L, Monge F, Patel K, Loomba R, Caldwell SH, et al. Correlations between hepatic morphometric collagen content, histologic fibrosis staging, and serum markers in patients with advanced fibrosis due to nonalcoholic steatohepatitis (NASH). Hepatol 2015; 62 (1): 906A.

  • Harrison SA, Goodman ZD, Ratziu V, Loomba R, Diehl AM, Lawitz E, et al. Serum lysyl oxidase-like-2 (sLOXL2) levels correlate with fibrosis stage in patients with nonalcoholic steatohepatitis (NASH). Hepatol 2015; 62 (1): 910A.

  • Sanyal AJ, Goodman ZD, Abdelmalek MF, Harrison SA, Rockey DC, Diehl AM, et al. Clinical and histologic correlates of the hepatic venous pressure gradient (HVPG) in patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH). Hepatol 2015; 62 (1): 577A.

  • Ratziu V, Sanyal AJ, Loomba R, Caldwell SH, Ghalib RH, Torres DM, et al. Characterization of insulin resistance in patients with advanced fibrosis due to nonalcoholic steatohepatitis (NASH). Hepatol 2015; 62 (1): 1298A-1299A.

  • Loomba R, Huang DQ, Sanyal AJ, Anstee QM, Trauner M, Lawitz EJ, Ding D, Ma L, Jia C, Billin A, Huss RS, Chung C, Goodman Z, Wong VW, Okanoue T, Romero-Gomez M, Abdelmalek MF, Muir A, Afdhal N, Bosch J, Harrison S, Younossi ZM, Myers RP. Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis. Gut. 2023 Mar;72(3):581-589. doi: 10.1136/gutjnl-2022-327777. Epub 2022 Sep 9.

    PubMed 36750244

  • Younossi ZM, Anstee QM, Wai-Sun Wong V, Trauner M, Lawitz EJ, Harrison SA, Camargo M, Kersey K, Subramanian GM, Myers RP, Stepanova M. The Association of Histologic and Noninvasive Tests With Adverse Clinical and Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis. Gastroenterology. 2021 Apr;160(5):1608-1619.e13. doi: 10.1053/j.gastro.2020.12.003. Epub 2020 Dec 8.

    PubMed 33307033

  • Harrison SA, Abdelmalek MF, Caldwell S, Shiffman ML, Diehl AM, Ghalib R, Lawitz EJ, Rockey DC, Schall RA, Jia C, McColgan BJ, McHutchison JG, Subramanian GM, Myers RP, Younossi Z, Ratziu V, Muir AJ, Afdhal NH, Goodman Z, Bosch J, Sanyal AJ; GS-US-321-0105 and GS-US-321-0106 Investigators. Simtuzumab Is Ineffective for Patients With Bridging Fibrosis or Compensated Cirrhosis Caused by Nonalcoholic Steatohepatitis. Gastroenterology. 2018 Oct;155(4):1140-1153. doi: 10.1053/j.gastro.2018.07.006. Epub 2018 Jul 7.

    PubMed 29990488

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SIM in people with Liver Fibrosis Due to NASH, run by Gilead Sciences at 59 sites in 8 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 10 inclusion and 17 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 27 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 59 sites in United States, France, Canada, Italy, United Kingdom and 3 more countries. 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 27 Mar 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?

Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) (time frame: Baseline to Week 96). The study lists 2 primary outcomes in all. 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 NCT01672879, which also lists 14 linked publications.

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 27 Mar 2019.

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