臨床研究等提出・公開システム

A Phase 2, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Study Evaluating the Safety and Efficacy of Semaglutide, and the Fixed-Dose Combination of Cilofexor and Firsocostat, Alone and in Combination, in Subjects With Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

Study Evaluating the Safety and Efficacy of Semaglutide, and the Fixed-Dose Combination of Cilofexor and Firsocostat, Alone and in Combination, in Participants With Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
(WAYFIND)

Kamiya Makoto

Gilead Sciences, K.K.

1-9-2, Marunouchi, Chiyoda-ku, Tokyo

ClinicalTrialGSJ@gilead.com

Clinical Operatoins

Gilead Sciences, K.K.

1-9-2, Marunouchi, Chiyoda-ku, Tokyo

+81-3-6837-0730

JPClinicalOperations@gilead.com

Not Recruiting

Dec. 20, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- Liver biopsy consistent with cirrhosis (F4) due to NASH in the opinion of the central reader.
- Screening laboratory parameters as determined by the study central laboratory:
- Estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73m2, as calculated by the Modification of Diet in Renal Disease (MDRD)equation
- HbA1c <= 10%
- INR <= 1.4, unless due to therapeutic anticoagulation
- Platelet count>= 125,000/uL
- Alanine Aminotransferase (ALT) < 5 x ULN
- Serum albumin >= 3.5 g/dL
- Serum Alkaline Phosphatase (ALP) <= 2 x ULN
- BMI >= 23 kg/ m2 at screening

- Prior history of decompensated liver disease, including ascites, hepatic encephalopathy (HE), or variceal bleeding
- Child-Pugh (CP) score > 6 at screening, unless due to an alternative etiology such as Gilberts syndrome or therapeutic anticoagulation
- Model for End-stage Liver Disease (MELD) score > 12 at screening, unless due to an alternative etiology such as therapeutic anticoagulation
- Other causes of liver disease based on medical history and/or central reader review of liver histology, including but not limited to: alcoholic liver disease, autoimmune disorders (eg, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency
- Chronic HBV infection (HBsAg positive), or Chronic HCV infection (HCV antibody and HCV RNA positive). Participants cured of HCV infection less than 2 years prior to the screening visit are not eligible
- History of liver transplantation
- Current or prior history of hepatocellular carcinoma (HCC)
- Men who habitually drink greater than 21 units/week of alcohol or women who habitually drink greater than 14 units/week of alcohol (one unit is equivalent to 12 oz/360 mL of beer, a 4 oz/120 mL glass of wine, or 1 oz/30 mL of hard liquor).
- For individuals on vitamin E regimen >= 800 IU/day, or pioglitazone, dose must be stable, in the opinion of the investigator for at least 180 days prior to the historical or screening liver biopsy
- For individuals on medications for diabetes, dose must be stable, in the opinion of the investigator, for at least 90 days prior to the historical or screening liver biopsy
- History of type 1 diabetes
- Treatment with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in the period from 90 days prior to the screening visit and for individuals with a qualifying historical liver biopsy, for 90 days prior to the date of the historical liver biopsy
- For participants who have not completed a series of an authorized COVID-19 vaccination regimen prior to screening, a positive result for COVID-19 on SARS-CoV-2 RT-PCR test

Both

Nonalcoholic Steatohepatitis

Experimental: SEMA + CILO/FIR FDC
Participants will receive semaglutide (SEMA) 0.24-2.4 mg once weekly as subcutaneous (SC) injection (dose escalation every 4 weeks) and fixed-dose combination (FDC) tablet of cilofexor and firsocostat (CILO/FIR 30 mg/20 mg) once daily as orally for 72 weeks

Experimental: SEMA + Placebo-To-Match (PTM) CILO/FIR
Participants will receive SEMA 0.24-2.4 mg once weekly (dose escalation every 4 weeks) and PTM CILO/FIR administered once daily for 72 weeks

Experimental: PTM SEMA + CILO/FIR FDC
PTM Semaglutide once weekly and CILO/FIR 30 mg/20 mg FDC administered once daily for 72 weeks

Placebo Comparator: PTM SEMA + PTM CILO/FIR
PTM Semaglutide once weekly and PTM CILO/FIR once daily for 72 weeks

1. Percentage of Participants Who Achieve >= 1-Stage Improvement in Fibrosis According to the NASH Clinical Research Network (CRN) Classification Without Worsening of NASH in Participants Treated With SEMA + CILO/FIR Versus Placebo
Worsening of NASH is defined as a >= 1-point increase in hepatocellular ballooning or lobular inflammation. [Time Frame: Week 72]
2. Percentage of Participants With NASH Resolution in Participants Treated with SEMA + CILO/FIR Versus Placebo
NASH resolution is defined as lobular inflammation of 0 or 1 and hepatocellular ballooning of 0. [Time Frame: Week 72]

1.Percentage of Participants With NASH Resolution In Participants Treated With SEMA+CILO/FIR Versus CILO/FIR Alone [Time Frame: Week 72]
2. Percentage of Participants Who Achieve >= 1-Stage Improvement in Fibrosis (According to the NASH CRN Classification) Without Worsening of NASH in Participants Treated With SEMA+CILO/FIR Versus SEMA Alone Worsening of NASH is defined as a >= 1-point increase in hepatocellular ballooning or lobular inflammation. [Time Frame: Week 72]

+81-952-34-2085

Nov. 08, 2021

No

US/Canada/France/Spain/Puerto Rico/Australia