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出境医 / 临床实验 / Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Adults With Nonalcoholic Steatohepatitis (NASH)

Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Adults With Nonalcoholic Steatohepatitis (NASH)

Study Description
Brief Summary:
The primary objective of this study is to evaluate the safety and tolerability of study drug(s) in adults with nonalcoholic steatohepatitis (NASH).

Condition or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis Drug: Semaglutide Drug: Firsocostat Drug: Cilofexor Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)
Actual Study Start Date : July 29, 2019
Actual Primary Completion Date : July 13, 2020
Actual Study Completion Date : July 13, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: Semaglutide
Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) for 24 weeks
 Drug: Semaglutide
Solution for injection administered subcutaneously once weekly
Experimental: Semaglutide + Firsocostat
Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) + firsocostat 20 mg for 24 weeks
 Drug: Semaglutide
Solution for injection administered subcutaneously once weekly

Drug: Firsocostat
Tablets administered orally once daily
Other Name: GS-0976
Experimental: Semaglutide + Cilofexor 30 mg
Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) + cilofexor 30 mg for 24 weeks
 Drug: Semaglutide
Solution for injection administered subcutaneously once weekly

Drug: Cilofexor
Tablets administered orally once daily
Other Name: GS-9674
Experimental: Semaglutide + Cilofexor 100 mg
Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) + cilofexor 100 mg for 24 weeks
 Drug: Semaglutide
Solution for injection administered subcutaneously once weekly

Drug: Cilofexor
Tablets administered orally once daily
Other Name: GS-9674
Experimental: Semaglutide + Firsocostat + Cilofexor
Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks
 Drug: Semaglutide
Solution for injection administered subcutaneously once weekly

Drug: Firsocostat
Tablets administered orally once daily
Other Name: GS-0976

Drug: Cilofexor
Tablets administered orally once daily
Other Name: GS-9674
Outcome Measures
Primary Outcome Measures :
  1. Number of Participants Who Experience Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade ≥ 1 Laboratory Abnormality [ Time Frame: First dose date up to Week 24 plus 30 days ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Historical liver biopsy consistent with NASH with stage 2-3 fibrosis according to NASH Clinical Research Network (CRN) classification OR clinical diagnosis of nonalcoholic fatty liver disease and screening FibroTest, magnetic resonance imaging - proton density fat fraction (MRI-PDFF), and FibroScan

  • Screening laboratory parameters, as determined by central laboratory:

    • Alanine aminotransferase (ALT) ≤ 5 x upper limit of the normal range (ULN)
    • Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as calculated by the Modification of Diet in Renal Disease (MDRD) study equation
    • HbA1c ≤ 9.5%
    • International normalized ratio (INR) ≤ 1.2, unless due to therapeutic anti-coagulation therapy
    • Platelet count ≥ 100,000/μL
    • Total bilirubin < 1.3 x ULN unless alternate etiology such as Gilbert's syndrome present
    • Calcitonin ≤ 100 ng/L
  • Body Mass Index (BMI) > 23 kg/m^2 and body weight of > 60 kg

Key Exclusion Criteria:

  • Any historical liver biopsy consistent with cirrhosis
  • Any history of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding
  • Other causes of liver disease, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment
  • History of liver transplantation
  • History of hepatocellular carcinoma
  • History of pancreatitis (acute or chronic)
  • Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
  • Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the period from 90 days prior to the date of the Screening Visit
  • Individuals on antidiabetic medications must be on a stable dose for at least 90 days prior to the date of the Screening Visit and in the period between the date of the Screening Visit and Enrollment (Day -14)

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

Contacts and Locations

Locations
Show Show 18 study locations
Sponsors and Collaborators
Gilead Sciences
Novo Nordisk A/S
Investigators
Layout table for investigator information
Study Director: Gilead Study Director Gilead Sciences
Tracking Information
First Submitted Date  ICMJE June 12, 2019
First Posted Date  ICMJE June 14, 2019
Last Update Posted Date December 11, 2020
Actual Study Start Date  ICMJE July 29, 2019
Actual Primary Completion Date July 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2019) 		Number of Participants Who Experience Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade ≥ 1 Laboratory Abnormality [ Time Frame: First dose date up to Week 24 plus 30 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Adults With Nonalcoholic Steatohepatitis (NASH)
Official Title  ICMJE A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)
Brief Summary The primary objective of this study is to evaluate the safety and tolerability of study drug(s) in adults with nonalcoholic steatohepatitis (NASH).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Nonalcoholic Steatohepatitis
Intervention  ICMJE
  • Drug: Semaglutide
    Solution for injection administered subcutaneously once weekly
  • Drug: Firsocostat
    Tablets administered orally once daily
    Other Name: GS-0976
  • Drug: Cilofexor
    Tablets administered orally once daily
    Other Name: GS-9674
Study Arms  ICMJE
  • Experimental: Semaglutide
    Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) for 24 weeks
    Intervention: Drug: Semaglutide
  • Experimental: Semaglutide + Firsocostat
    Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) + firsocostat 20 mg for 24 weeks
    Interventions:
    • Drug: Semaglutide
    • Drug: Firsocostat
  • Experimental: Semaglutide + Cilofexor 30 mg
    Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) + cilofexor 30 mg for 24 weeks
    Interventions:
    • Drug: Semaglutide
    • Drug: Cilofexor
  • Experimental: Semaglutide + Cilofexor 100 mg
    Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) + cilofexor 100 mg for 24 weeks
    Interventions:
    • Drug: Semaglutide
    • Drug: Cilofexor
  • Experimental: Semaglutide + Firsocostat + Cilofexor
    Semaglutide 0.24 mg - 2.4 mg (dose escalation every 4 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks
    Interventions:
    • Drug: Semaglutide
    • Drug: Firsocostat
    • Drug: Cilofexor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 20, 2019) 		109
Original Estimated Enrollment  ICMJE
 (submitted: June 12, 2019) 		100
Actual Study Completion Date  ICMJE July 13, 2020
Actual Primary Completion Date July 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Historical liver biopsy consistent with NASH with stage 2-3 fibrosis according to NASH Clinical Research Network (CRN) classification OR clinical diagnosis of nonalcoholic fatty liver disease and screening FibroTest, magnetic resonance imaging - proton density fat fraction (MRI-PDFF), and FibroScan

  • Screening laboratory parameters, as determined by central laboratory:

    • Alanine aminotransferase (ALT) ≤ 5 x upper limit of the normal range (ULN)
    • Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as calculated by the Modification of Diet in Renal Disease (MDRD) study equation
    • HbA1c ≤ 9.5%
    • International normalized ratio (INR) ≤ 1.2, unless due to therapeutic anti-coagulation therapy
    • Platelet count ≥ 100,000/μL
    • Total bilirubin < 1.3 x ULN unless alternate etiology such as Gilbert's syndrome present
    • Calcitonin ≤ 100 ng/L
  • Body Mass Index (BMI) > 23 kg/m^2 and body weight of > 60 kg

Key Exclusion Criteria:

  • Any historical liver biopsy consistent with cirrhosis
  • Any history of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding
  • Other causes of liver disease, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment
  • History of liver transplantation
  • History of hepatocellular carcinoma
  • History of pancreatitis (acute or chronic)
  • Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
  • Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the period from 90 days prior to the date of the Screening Visit
  • Individuals on antidiabetic medications must be on a stable dose for at least 90 days prior to the date of the Screening Visit and in the period between the date of the Screening Visit and Enrollment (Day -14)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03987074
Other Study ID Numbers  ICMJE GS-US-454-5533
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Novo Nordisk A/S
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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