A study to assess the safety and efficacy of Semaglutide and the fixed dose combination of Cilofexor and Firsocostat, alone and in combination, in subjects with Chirrhosis due to Nonalcoholic Steatohepatitis (NASH)
- Conditions
- onalcoholic Steatohepatitis (NASH)MedDRA version: 24.1Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2021-001445-12-ES
- Lead Sponsor
- Gilead Sciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 440
1)Men and women between 18 and 80 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
3)Cirrhosis (F4) due to NASH as defined in the protocol
4)The following laboratory parameters at screening, as determined by the central laboratory:
a)Estimated glomerular filtration rate (eGFR) = 30 mL/min/1.73m2, as calculated by the Modification of Diet in Renal Disease (MDRD) equation to estimate creatinine clearance (CLcr)
b)HbA1c = 10% (or serum fructosamine = 400 umol/L if HbA1c is not quantifiable)
c)Hemoglobin > 10.6 g/dL
d)INR = 1.4, unless due to therapeutic anticoagulation
e)Total bilirubin = 1.3 x ULN (unless due to an alternative etiology such as Gilbert’s syndrome or hemolytic anemia)
f)Serum albumin = 3.5 g/dL
g)Serum ALP = 2 x ULN
h)Platelet count = 125,000/uL
i)Serum triglyceride level = 250mg/dL. If initial screening value is >250 mg/dL, triglycerides may be retested during the screening period. Fasting serum triglycerides must be confirmed to be = 250 mg/dL prior to Day 1. Management of hypertriglyceridemia may be initiated or modified at investigator discretion during the screening period (Section 7.7.4.1).
j)ALT < 5 x ULN
5)BMI = 23 kg/m2 at screening
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 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110
1)Any history of decompensated liver disease in the opinion of the investigator, including clinically relevant ascites, hepatic encephalopathy (HE), or variceal bleeding
2)Child-Pugh (CP) score > 6 at screening, unless due to an alternative etiology such as Gilbert’s syndrome or therapeutic anticoagulation
3)Model for End-stage Liver Disease (MELD) score >12 at screening, unless due to an alternative etiology such as therapeutic anticoagulation
4)Chronic HBV infection (HBsAg positive)
5)Chronic HCV infection (HCV antibody and HCV RNA positive). Subjects cured of HCV infection less than 2 years prior to the screening visit are not eligible.
6)Other causes of liver disease based on medical history and/or central pathologist review of liver histology, including but not limited to: alcoholic liver disease, autoimmune disorders (eg, PBC, PSC, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency
7)History of liver transplantation
8)Current or prior history of HCC
9)HIV infection
10)Weight loss >10% within 180 days of screening, or >5% between the date of the biopsy used for eligibility and the date of screening
11)Any weight reduction surgery or procedure in the 2 years prior to screening or malabsorptive weight loss surgery (eg, Roux-en-Y or distal gastric bypass) at any time prior to screening
12)History of intestinal resection that could result in malabsorption of study drug
13)Planned coronary, carotid, or peripheral artery intervention or unstable cardiovascular disease in the opinion of the investigator
14)History of uncontrolled chronic pulmonary disease in the opinion of the investigator within 180 days prior to screening
15)Men who habitually drink greater than 21 units/week of alcohol or women who habitually drink greater than 14 units/week of alcohol
16)Positive urine drug screen for amphetamines, cocaine, or opiates at screening, unless due to a prescription medication
17)Use of any prohibited concomitant medication prior to enrollment
18)Participation in another investigational study of a drug or device within 30 days or within 5 half-lives of the prior investigational agent (whichever is longer) prior to the date of screening and through the end of the study. Participation in a study of an investigational device may be approved by the medical monitor or designee.
19)History of malignancy within 5 years of screening with the following exceptions:
a)Adequately treated carcinoma in situ of the cervix
b)Adequately treated basal or squamous cell cancer or other localized nonmelanoma skin cancer
20)For subjects with type 2 diabetes diagnosed prior to the date of the screening visit OR based on screening visit results (HbA1c = 6.5% or fasting plasma glucose = 126 mg/dL, confirmed on repeat testing), subjects must have no evidence of uncontrolled and potentially unstable retinopathy or maculopathy as determined by a fundoscopic examination performed starting 90 days prior to screening visit date through Day 1. If there has been worsening of the subject’s visual function since a historical fundoscopic examination in the opinion of the investigator, then the fundoscopic examination must be repeated prior to Day 1 for eligibility. Pharmacological pupil dilation is a requirement unless using a digital fundus photography camera specified for nondilated examination.
21)Acute pancreatitis within 180 days prior to screening
22)History or presence of chroni
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method