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Liver Fibrosis Due to NASHPhase 2NCT01672866

Safety and Efficacy of Simtuzumab (SIM, GS-6624) in Adults With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

A Phase 2 study testing SIM in people with Liver Fibrosis Due to NASH, run by Gilead Sciences at 68 sites in 9 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 whether SIM (formerly referred to as GS-6624) is effective at preventing the histologic progression of liver fibrosis and the clinical progression to cirrhosis in participants with NASH. 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
222 participants
Where
68 sitesin 9 countries
Study dates
5 Dec 2012to 29 Dec 2016
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 chronic liver disease due to NASH defined as macrovesicular steatosis involving > 5% of hepatocytes on a liver biopsy with associated lobular inflammation
  • Stage 3-4 fibrosis by Ishak score on a liver biopsy
  • Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
  • Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x Central Laboratory Upper Limit of Normal (clULN)
  • Must have serum creatinine < 2.0 mg/dL
  • A negative serum pregnancy test is required for females of childbearing potential
Show all 9Show fewer
  • All sexually active females of childbearing potential must agree to use a protocol recommended method of contraception during 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
  • Males, 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
  • Cirrhosis of the liver
  • Any history of hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding
  • Weight reduction surgery in the past 5 years
  • 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.
  • 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 individual's compliance with the protocol procedures;
  • Participation in an investigational trial of a drug or device within 30 days prior to screening
  • BMI < 18 kg/m^2
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

68 sites in 9 countries.

68 sites in 9 countries

United States41 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Texas Clinical Research Institute, LLC

    Arlington, Texas, 76012

  • University of Colorado

    Aurora, Colorado, 80045

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • State University Of New York

    Buffalo, New York, 14203

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • Northwestern University

    Chicago, Illinois, 60611

  • University Hospitals Case Medical Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Iowa Digestive Disease Center

    Clive, Iowa, 50325

  • Southern California Liver Centers

    Coronado, California, 92118

  • Duke University

    Durham, North Carolina, 27710

  • Brooke Army Medical Center

    Fort Sam Houston, Texas, 78234

  • St. Luke's Episcopal Hospital

    Houston, Texas, 77030

  • Indianapolis Gastroenterology Research Foundation

    Indianapolis, Indiana, 46237

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • University of Louisville

    Louisville, Kentucky, 40202

  • Miami Veterans Administration Healthcare System

    Miami, Florida, 33136

  • Tulane University

    New Orleans, Louisiana, 70112

  • Weill Cornell Medical College

    New York, New York, 10021

  • Mount Sinai Hospital

    New York, New York, 10029

  • Liver Institute of Virginia

    Newport News, Virginia, 23602

  • Digestive and Liver Disease Specialists

    Norfolk, Virginia, 23502

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • University Gastroenterology

    Providence, Rhode Island, 02905

  • Bucheon St. Marys Hospital

    Richmond, Virginia, 23229

  • Virginia Commonwealth University Health System

    Richmond, Virginia, 23298

  • Minnnesota Gastroenterology, PA

    Saint Paul, Minnesota, 55114

  • University of Utah

    Salt Lake City, Utah, 84132

  • 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

United Kingdom5 sites

  • John Radcliffe Hospital

    Headington, OX3 9DU

  • The Royal London Hospital

    London, E1 1BB

  • Royal Free Hospital, Pond Street

    London, NW3 2QG

  • King's College Hospital NHS Foundation Trust No. 1 Account

    London, SE5 9RS

  • Nottingham University Hospitals Queens Medica

    Nottingham, NG7 2UH

Other trials in United Kingdom

Canada4 sites

  • University of Calgary

    Calgary, Alberta, T2N 4Z6

  • London Health Science Center

    London, Ontario, N6A 5A5

  • Toronto Liver Centre

    Toronto, Ontario, M6H 3M1

  • University of Manitoba

    Winnipeg, Manitoba, R3E 3P4

Other trials in Canada

France4 sites

  • Hopital Beaujon

    Clichy, 92110

  • Hospital Saint-Antoine

    Paris, 75012

  • Groupe Hospitalier Pitié- Salpétrière

    Paris, 75013

  • CHU Strasbourg Hôpital Civil

    Strasbourg, 67091

Other trials in France

Spain4 sites

  • Hospital Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital Donostia

    Donostia / San Sebastian, 20080

  • Hospital Universitario Puerta de Hierro

    Majadahonda, 28222

Other trials in Spain

Belgium3 sites

  • Hôpital Erasme

    Brussels, 1070

  • Université Catholique de Louvain

    Brussels, 1200

  • UZ Ghent

    Ghent, B-9000

Other trials in Belgium

Germany3 sites

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Gastroenterologisch-Hepatologisches Zentrum Kiel

    Kiel, 24146

  • EUGASTRO GmbH

    Leipzig, 4103

Other trials in Germany

Italy3 sites

  • Azienda Ospedaliero-Universitaria di Modena Policlinico

    Modena, 41100

  • Azienda Ospedaliera San Camillo Forlanini

    Roma, 152

  • Azienda Ospedaliera Città della Salute e della Scienza di Torino

    Torino, 10126

Other trials in Italy

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 Molecule 2 (LOXL2), in Subjects With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

The primary objective of this study is to evaluate whether SIM (formerly referred to as GS-6624) is effective at preventing the histologic progression of liver fibrosis and the clinical progression to cirrhosis in participants with NASH.

It will consist of 2 phases:

  • Randomized Double-Blind Phase
  • Open-Label Phase (optional)
Being tested
Placebo, SIM
Keywords
NASH, noncirrhotic, Monoclonal antibody, LOXL2, Simtuzumab, Nonalcoholic Steatohepatitis, NAFLD, Liver biopsy, MRE, Liver fibrosis, Ishak
Medical subject headings
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 via subcutaneous injection every week

  • SIMBiological

    Also called GS-6624

    Subcutaneous injection every week

Study groups in NCT01672866
Study groupRoleWhat they receive
SIM 75 mgExperimentalDuring the Randomized Double-Blind Phase, participants will receive SIM 75 mg via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to an additional 240 weeks.
Receives: Biological: SIM
SIM 125 mgExperimentalDuring the Randomized Double-Blind Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to an additional 240 weeks.
Receives: Biological: SIM
PlaceboPlacebo comparatorDuring the Randomized Double-Blind Phase, participants will receive placebo to match SIM via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly 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 MQC on Liver Biopsy

    Measured: Baseline to Week 96

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

    The EFS was the primary clinical efficacy endpoint and was assessed by the time to progression to cirrhosis. Participants were considered to have become cirrhotic if they had a post-baseline biopsy consistent with cirrhosis or developed overt signs and symptoms of cirrhosis. All overt signs and symptoms went through an adjudication process and were confirmed before they were considered for the EFS analysis.

    Measured: Baseline up to the time of progression to cirrhosis or last dose date (maximum: 240 weeks in the 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 start5 Dec 2012
  3. Primary completion2 Aug 2016
  4. Study completion29 Dec 2016

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
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
222 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01672866
Sponsor's protocol ID
GS-US-321-0105
Other IDs
2012-002488-88
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.

  • Ratziu V, Sanyal A, Torres D, Hinrichsen H, Serfaty L, Bambha K, et al. Impact of weight reduction on serum markers and liver histology including progression to cirrhosis in patients with nonalcoholic steatohepatitis (NASH) and bridging fibrosis. J Hepatol 2017; 66 (1): S594.

  • 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.

  • 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.

  • 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 68 sites in 9 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 9 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 68 sites in United States, United Kingdom, Canada, France, Spain and 4 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 MQC on Liver Biopsy (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 NCT01672866, which also lists 11 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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