GS-US-321--0105

Principal Investigator: Juan  Gallegos-Orozco
Keywords: Fatty Liver , Nonalcoholic Steatohepatitis (NASH) , NAFLD , Liver Disease , non-cirrhotic , Digestive System Diseases Department: Gastroenterology
IRB Number: 00068209 Co Investigator:  
Specialty: Gastroenterology, Gastroenterology, Gastroenterology, Gastroenterology
Sub Specialties: Liver Disease, Liver Biopsies, Hepatology
Recruitment Status: Active, not recruiting

Contact Information

Tiffany Tomkinson
tiffany.tomkinson@hsc.utah.edu
801-585-9155

Brief Summary

The primary objective of this study is:

  • To evaluate whether simtuzumab is effective at preventing the histological progression of liver fibrosis and the clinical progression to cirrhosis in subjects with NASH.

The exploratory objectives of this study are:

·         To assess the safety of simtuzumab in subjects with NASH;

·         To assess the immunogenicity of simtuzumab in this population;

·         To assess whether baseline LOXL2 levels are predictive of response to simtuzumab therapy (active arms) and/or prognostic for disease progression (placebo arm);

·         To compare different efficacy assessment tools in this population;

·         To determine whether non-invasive measures of fibrosis can predict histologic regression of fibrosis and prevention of progression to cirrhosis in this population.

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in
this study.
 
1. Males and females 18 - 65 years of age;
 
2. Be willing and able to provide written informed consent;
 
3. Have chronic liver disease due to NASH defined as macrovesicular steatosis involving >5% of hepatocytes on a liver biopsy with associated lobular inflammation;
 
4. Stage 3-4 fibrosis by Ishak score on a liver biopsy. If the subject is deemed ineligible for this study, the liver biopsy, if performed according to protocol specifications and is within 3 months of the screening visit, may be used to determine eligibility for the GS-US-321-0106 study (another Gilead Sciences NASH study that also must be IRB/EC approved at participating centers);
 
5. Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease;
 
6. Must be willing and able to comply with all study requirements;
 
7. Must have AST and ALT ≤ 10 x clULN (refer to the central laboratory manual for normal ranges);
 
8. Must have serum creatinine < 2.0 mg/dL;
 
9. Female subjects of childbearing potential must have a negative serum pregnancy test prior to starting study treatment. For the purposes of this study, a female subject of child-bearing potential is a woman who has not had a hysterectomy, bilateral oophorectomy, or medically-documented ovarian failure. Women ≤ 50 years of age with amenorrhea of any duration will be considered to be of childbearing potential;
 
10. All female subjects who are of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the study period and for 90 days following the last dose of study drug. If females utilize hormonal agents as one of their contraceptive methods, the same hormonal method must have been used for at least 1 month before study dosing. Females on hormonal methods must also utilize a barrier method as another form of contraception (See Section 7.11.2);
 
11. Lactating females must agree to discontinue nursing before starting study treatment.
 
12. 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.

Exclusion Criteria

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

  1. Pregnant or breast feeding;
  2. Cirrhosis of the liver
  3. Any history of hepatic decompensation, including ascites, hepatic encephalopathy or variceal bleeding;
  4. Weight reduction surgery in the past 5 years;
  5. HCV RNA positive;
  6. HBsAg positive;
  7. Alcohol consumption greater than 21oz/week for males or 14oz/week for females (1oz/25mL of alcohol is present in 1 12oz/300mL beer, 1 4oz/125mL glass of wine, and a 1 oz/25mL measure of 40% proof alcohol)
  8. 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;
  9. Clinically significant cardiac disease;
  10. History of malignancy, other than non-melanomatous skin cancer, within 5 years prior to screening;

11.Major surgical procedure within 30 days prior to screening or the presence of an open wound;

12.Known hypersensitivity to the investigation product or any of its formulation excipients;

13.History of bleeding diathesis within 6 months of screening;

14.Unavailable for follow-up assessment or concern for subject’s compliance with the protocol procedures;

15.Participation in an investigational trial of a drug or device within 30 days prior to screening;

16.Any other condition that in the opinion of the investigator renders the subject a poor risk for inclusion into the study;

17.BMI < 18 kg/m2;