A Clinical trial to evaluate safety, and effectiveness of GS-4997 in combination with an existing therapy (prednisolone) vs prednisolone alone in subjects with Severe Alcoholic Hepatitis

Phase 1

• Conditions: Alcoholic Hepatitis; MedDRA version: 19.0 Level: LLT Classification code 10001624 Term: Alcoholic hepatitis System Organ Class: 100000004871; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2016-000821-37-GB
• Lead Sponsor: Gilead Sciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-09-30
• Study Completion: 2018-05-31
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 104

Inclusion Criteria

1) Males and non-pregnant, non-lactating females between 18-70 years of age, inclusive based on the date of the screening visit;
2) Willing and able to give informed consent prior to any study specific procedures being performed. In subjects with hepatic encephalopathy (HE), which may impair decision-making, consent will be obtained per hospital procedures (eg, by legal Authorized Representative);
3) Clinical diagnosis of severe AH
4) All female subjects 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 methods must have been used for at least 3 months before study dosing. Females on hormonal methods must also utilize a barrier method as another form of contraception;
5) Male subjects must refrain from sperm donation from screening through at least 90 days following the last dose of study drug;
6) Male subjects must agree to use condoms during intercourse from screening through study completion and for 90 days following the last dose of study drug;
7) Female subjects must refrain from egg donation or harvest for 90 days after last dose of study drug;
8) Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions
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 108
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion Criteria

1) Pregnant or lactating females;
2) Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen [HBsAg] positive), chronic hepatitis C (HCV RNA positive), acetaminophen hepatotoxicity, biliary obstruction, and autoimmune liver disease;
3) Serum AST >400 U/L or ALT >300 U/L;
4) MELD >30 at screening;
5) Maddrey’s DF >60 at screening;
6) Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria;
7) Concomitant or previous history of hepatocellular carcinoma;
8) History of liver transplantation;
9) HIV Ab positive;
10) Uncontrolled sepsis;
11) Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding within 7 days of screening that was associated with shock or required transfusion of more than 3 units of blood;
12) Type 1 hepatorenal syndrome (HRS) or renal failure defined as a serum creatinine >221 µmol/L (> 2.5 mg/dL) or the requirement for renal replacement therapy;
13) Subjects dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation);
14) Portal vein thrombosis;
15) Acute pancreatitis;
16) Cessation of alcohol consumption for more than 2 months before baseline/Day 1;
17) Severe associated disease (eg, cardiac failure, acute myocardial infarction, severe cardiac arrhythmias, severe pulmonary disease, neurologic disease,) that may lead to premature mortality within the study period;
18) Malignancy within the 2 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible.
19) Positive urine screen for amphetamines, cocaine or opiates (ie, 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 positive cannabis drug screen 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;
20) Treatment with immunosuppressive drugs [eg, systemic corticosteroids (inhaled and topical steroids are allowed), budesonide, tacrolimus, sirolimus, cyclosporine, azathioprine, mycophenolate mofetil, and methotrexate], pentoxifylline, or N-acetylcysteine (NAC) within 6 month of screening;
21) Use of the following CYP3A4 inhibitors (clarithromycin, conivaptan, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, bupenorphine/naloxone, telithromycin, voriconazole) or CYP3A4 inducers (carbamazepine, phenytoin, rifampin, St. John’s Wort) within 2 weeks of baseline;
22) Active ocular herpes simplex;
23) Any laboratory abnormality or condition that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results;
24) Participation in another investigational study of a drug or device within 1 month prior or within 5 half-lives of the prior investigational agent (whic

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified