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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04971785




Registration number
NCT04971785
Ethics application status
Date submitted
20/07/2021
Date registered
21/07/2021

Titles & IDs
Public title
Study of Semaglutide, and Cilofexor/Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)
Scientific title
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)
Secondary ID [1] 0 0
2021-001445-12
Secondary ID [2] 0 0
GS-US-454-6075
Universal Trial Number (UTN)
Trial acronym
WAYFIND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonalcoholic Steatohepatitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Semaglutide (SEMA)
Treatment: Drugs - Cilofexor (CILO)/Firsocostat (FIR)
Treatment: Drugs - PTM SEMA
Treatment: Drugs - PTM CILO/FIR

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


Treatment: Drugs: Semaglutide (SEMA)
Administered as subcutaneous (SC) injection

Treatment: Drugs: Cilofexor (CILO)/Firsocostat (FIR)
Tablets administered orally

Treatment: Drugs: PTM SEMA
Administered as SC injection

Treatment: Drugs: PTM CILO/FIR
Tablets administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Week 72
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Week 72
Secondary outcome [2] 0 0
Percentage of Participants With NASH Resolution in Participants Treated with SEMA+CILO/FIR Versus Placebo
Timepoint [2] 0 0
Week 72
Secondary outcome [3] 0 0
Percentage of Participants With NASH Resolution In Participants Treated With SEMA+CILO/FIR Versus CILO/FIR Alone
Timepoint [3] 0 0
Week 72

Eligibility
Key inclusion criteria
Key

* Liver biopsy consistent with cirrhosis (F4) due to nonalcoholic steatohepatitis (NASH) in the opinion of the central reader. In individuals who have never had a liver biopsy, a screening liver biopsy may be performed.
* Screening laboratory parameters as determined by the study central laboratory:

* Estimated glomerular filtration rate (eGFR) = 30 mL/min/1.73m^2, as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
* HbA1c = 10%
* International normalized ratio (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
* Body mass index (BMI) = 23 kg/m^2 at screening.

Key
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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 Gilbert's 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 hepatitis B virus (HBV) infection (HBsAg positive), or Chronic hepatitis C virus (HCV) infection (HCV antibody and HCV ribonucleic acid (RNA) positive). Individuals 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 (1 unit is equivalent to 12 ounce (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 individuals who have not completed a series of an authorized coronavirus disease 2019 (COVID-19) vaccination regimen prior to screening, a positive result for COVID-19 on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) test.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
457
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [5] 0 0
Eastern Health, Box Hill Hospital - Box Hill
Recruitment hospital [6] 0 0
Monash Health, Monash Medical Centre (Clayton) - Clayton
Recruitment hospital [7] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
5042 - Adelaide
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
6000 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Arkansas
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California
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Connecticut
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Illinois
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Indiana
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Iowa
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Kansas
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Louisiana
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Maryland
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Massachusetts
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Hamilton
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London
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Amiens
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Creteil
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Rennes
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Toulouse
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France
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Vandoeuvre les Nancy
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Japan
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Fukui
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Izunokuni
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Kyoto
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Japan
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Musashino-city
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Osaka
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Saga-shi
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Sapporo-shi
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Suita
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Tokyo
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Toon-Shi
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Yamagata
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Yokohama-shi
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Puerto Rico
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San Juan
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Barcelona
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Almeria
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Madrid
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Majadahonda
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Pontevedra
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Santander
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Santiago De Compostella
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Sevilla
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Spain
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Valencia
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Spain
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Valladolid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Novo Nordisk A/S
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04971785