An investigational study to assess the safety and efficacy of a new investigational drug in subjects with liver fibrosis but no liver cirrhosis secondary to non-alcoholic steatohepatitis (NASH)

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2012-002488-88-BE
• Date of registration: 02/09/2013
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences Inc
• Public title: An investigational study to assess the safety and efficacy of a new investigational drug in subjects with liver fibrosis but no liver cirrhosis secondary to non-alcoholic steatohepatitis (NASH)
• Scientific 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 Advanced Liver Fibrosis but not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)
• Date of first enrolment: 19/12/2013
• Target sample size: 225
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002488-88
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
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 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 intercourse from the screening through the study completion
and for 90 days following the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 225
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnant or breast feeding;
2. Cirrhosis of the liver;
3. Any history of hepatic decompensation, including ascites, hepatic encephalopathy, 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced Liver Fibrosis Secondary to Non-Alcoholic Steatohepatitis (NASH)
MedDRA version: 18.0 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Code: GS-6624
Pharmaceutical Form: Solution for injection
INN or Proposed INN: GS-6624
Current Sponsor code: GS-6624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 75-
INN or Proposed INN: GS-6624
Other descriptive name: GS-6624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The primary efficacy end point is week 96

The clinical efficacy endpoint is event free survival (EFS). Subjects will be followed for up to 240 weeks. EFS is assessed by time to progression to cirrhosis.

Secondary Objective: 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.

Primary end point(s): Primary Efficacy Endpoint
The primary efficacy endpoint is change from baseline in morphometric quantitative collagen (MQC) on liver biopsy at Week 96.

Clinical Efficacy Endpoint
The clinical efficacy endpoint is event free survival (EFS). Subjects will be followed for up to 240 weeks. EFS is assessed by time to progression to cirrhosis.

Main Objective: To evaluate whether simtuzumab (formerly referred to as GS-6624 ) is effective at preventing the histologic progression of liver fibrosis and the clinical progression to cirrhosis in subjects with NASH.

Secondary Outcome(s)

Secondary end point(s): Exploratory efficacy endpoints are:
- Change from baseline in modified Ishak fibrosis stage on liver biopsy at Weeks 48, 96 and 240;
- Change from baseline in Brunt/Kleiner fibrosis stage on liver biopsy at Week 48, 96 and 240;
- Change from baseline in NAS on liver biopsy at Week 48, 96 and 240;

Timepoint(s) of evaluation of this end point: Liver biopsy at Weeks 48, 96 and 240

Secondary ID(s)

NCT01672866

2012-002488-88-IT

GS-US-321-0105

Source(s) of Monetary Support

Gilead Sciences Inc