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A Phase 2, Multicenter, Placebo-Controlled, Randomized, Double-Blind, 48-Week Study to Evaluate the Efficacy and Safety of Combination Therapy of K-877-ER and CSG452 in Patients with Noncirrhotic Nonalcoholic Steatohepatitis (NASH) with Liver Fibrosis
EU CTIS ID: 2023-508104-38-00
What this study is testing
The primary objective of this study is to evaluate the superiority of K-001 QD (combination therapy of K-877-ER 0.4 mg QD and CSG452 20 mg QD) compared with placebo in histological primary efficacy endpoint at Week 48 when K-001 or placebo are administered for 48 weeks in subjects with noncirrhotic NASH with liver fibrosis.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Able to understand and comply with study procedures and give written informed consent
- Age ≥18 years
- NAS ≥4 with a score of at least 1 in each component of the NAS (steatosis, lobular inflammation, and ballooning) at the baseline biopsy, or a historical liver biopsy performed within 24 weeks of randomization
- Fibrosis stage of 1 or greater and below 4 on NASH CRN fibrosis staging system at the baseline biopsy, or a historical liver biopsy performed within 24 weeks of randomization
- Subject can be with or without T2DM, but T2DM subjects must be well controlled on a stable dose of antidiabetic medication for at least 8 weeks prior to Visit 1 or without medication. Subjects without T2DM must have fasting plasma glucose ≥90 mg/dL at Visit 1. A single repeat measurement is permitted, excluding those caused by invalid measurements such as, but not limited to, hemolysis, lost samples, sample contamination, or non-fasting blood draw, which are deemed outside of the single repeat.
- Female subjects must not be breastfeeding and must have a negative serum pregnancy test at Visit 1 if they are women of childbearing potential.
You likely can't join if
- Participation in another clinical trial involving an investigational agent within 30 days prior to signing the ICF for this study.
- Initiation of, or change in, current TG-lowering therapy within 8 weeks before Visit 1, or if a historical liver biopsy performed more than 8 weeks before Visit 1 is used, from the date of the liver biopsy until Visit 1. TG-lowering therapy is defined as niacin >100 mg/day, or dietary supplements or prescription of omega-3 fatty acids >1000 mg/day
- Initiation of, or change in, current doses of orlistat, phentermine, topiramate, naltrexone, or bupropion or any other medication that could promote weight loss in the opinion of the investigator within 8 weeks before Visit 1, or if a historical liver biopsy performed more than 8 weeks before Visit 1 is used, from the date of the liver biopsy until Visit 1
- Subjects with severe infections, during a perioperative period, or with serious injuries
- Subjects with urinary tract infection or genital infection
- Subjects with active current symptomatic gallstone disease
See the full eligibility criteria
Who can join
- Able to understand and comply with study procedures and give written informed consent
- Age ≥18 years
- NAS ≥4 with a score of at least 1 in each component of the NAS (steatosis, lobular inflammation, and ballooning) at the baseline biopsy, or a historical liver biopsy performed within 24 weeks of randomization
- Fibrosis stage of 1 or greater and below 4 on NASH CRN fibrosis staging system at the baseline biopsy, or a historical liver biopsy performed within 24 weeks of randomization
- Subject can be with or without T2DM, but T2DM subjects must be well controlled on a stable dose of antidiabetic medication for at least 8 weeks prior to Visit 1 or without medication. Subjects without T2DM must have fasting plasma glucose ≥90 mg/dL at Visit 1. A single repeat measurement is permitted, excluding those caused by invalid measurements such as, but not limited to, hemolysis, lost samples, sample contamination, or non-fasting blood draw, which are deemed outside of the single repeat.
- Female subjects must not be breastfeeding and must have a negative serum pregnancy test at Visit 1 if they are women of childbearing potential.
What rules you out
- Participation in another clinical trial involving an investigational agent within 30 days prior to signing the ICF for this study.
- Initiation of, or change in, current TG-lowering therapy within 8 weeks before Visit 1, or if a historical liver biopsy performed more than 8 weeks before Visit 1 is used, from the date of the liver biopsy until Visit 1. TG-lowering therapy is defined as niacin >100 mg/day, or dietary supplements or prescription of omega-3 fatty acids >1000 mg/day
- Initiation of, or change in, current doses of orlistat, phentermine, topiramate, naltrexone, or bupropion or any other medication that could promote weight loss in the opinion of the investigator within 8 weeks before Visit 1, or if a historical liver biopsy performed more than 8 weeks before Visit 1 is used, from the date of the liver biopsy until Visit 1
- Subjects with severe infections, during a perioperative period, or with serious injuries
- Subjects with urinary tract infection or genital infection
- Subjects with active current symptomatic gallstone disease
- Subjects with severe renal impairment at Visit 1, who are receiving dialysis at Visit 1, or who have had a kidney transplant, regardless of level of renal function
- Subjects with weight change of 5% or more: 1) between Visit 1 to Visit 2 and or 2) between Visit 2 to Visit 3 (randomization)
- Subjects who performed significant attempt to change diet and exercise, at the investigator’s opinion, within 12 weeks of Screening
- Model for End-stage Liver Disease (MELD) score >12 at Visit 1
- Presence of clinical or histological evidence of compensated cirrhosis, or biochemical evidence of compensated cirrhosis
- Ongoing or recent consumption of greater than moderate amounts of alcohol, or Alcohol Use Disorders Identification Test – Concise (AUDIT-C) score ≥3 in females or ≥4 in males during the Screening Period. Greater than moderate alcohol consumption is defined as on average >1 standard drink per day in women and on average >2 standard drinks per day in men over a 1-year period prior randomization. A standard alcoholic drink is any drink that contains about 14 g of pure alcohol.
- Inability to safely obtain a liver biopsy
- History or evidence of major and clinically significant, cardiovascular, pulmonary, renal, hematologic, gastrointestinal (including clinically significant malabsorption), endocrine (other than T2DM), immunologic, dermatologic, neurologic, psychiatric, oncologic, or allergic (including drug allergies but excluding untreated or treated seasonal allergies at the time of dosing) disease that would interfere with the conduct of the study, subject’s safety, or interpretation of the data
- Ongoing or history of malignancy within the past 5 years, except for basal or squamous cell skin carcinoma or any other carcinoma in situ, that has undergone curative therapy, and prostate cancer that has been managed through active surveillance or watchful waiting
- Any past history of HCC and/or HCC treatment
- History of bariatric surgery within 5 years of Screening
- Uncontrolled hypertension at Visit 1 (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg after 5 minutes of sitting)
- Subjects with evidence of portal hypertension (eg, low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly)
- Known infection with human immunodeficiency virus (HIV) 1 or HIV 2
- Known hypersensitivity or intolerance to fibrates, PPARα agonists, or SGLT2 inhibitors
- Anticipation of major surgery during the study
- Evidence of other forms of chronic liver disease as follows: a. Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg) b. History of hepatitis C treatment within 5 years of Screening, or active Hepatitis C as defined by presence of hepatitis C virus RNA c. Ongoing autoimmune liver disease based on historical evidence of diagnosis d. Primary biliary cirrhosis e. Primary sclerosing cholangitis f. Wilson’s disease based on historical evidence of diagnosis g. Alpha-1-antitrypsin deficiency based on historical evidence of diagnosis h. Hemochromatosis based on historical evidence of diagnosis or historical evidence of iron overload as defined by the presence of 3+ or 4+ stainable iron on liver biopsy i. Drug-induced liver disease as defined by typical exposure and history j. Known condition that involves bile duct obstruction k. Suspected or proven liver cancer l. Any type of liver disease other than NASH
- Current or anticipated chronic use of cyclosporine, rifampicin, or other inhibitors of OATP1B1, or OATP1B3
- Thyroid diseases such as active hyperthyroidism, clinical evidence of untreated hypothyroidism with thyroid-stimulating hormone values >7 IU/L with hypothyroid symptoms or >10 × IU/L without symptoms, or thyroid hormone therapy that is not stable for at least 6 weeks prior to Screening
- ALT and/or AST >200 IU/L at Visit 1
- ALT instability during the Screening Period, defined as a substantial change in ALT from Visit 1 to Visit 2 (Visit 2 ALT is both >50% AND >50 IU/L different from Visit 1 ALT). In such cases, Visit 2.1 must be scheduled by the Investigator at least 2 weeks after Visit 2 to re-test ALT once, unless the subject failed Screening due to meeting other exclusion criteria. If ALT level at Visit 2.1 is not substantially different from Visit 1 or Visit 2 values and does not suggest clinically significant ALT instability and/or clinically unfavorable trend in the opinion of the Investigator, the subject will be allowed to participate in the study
- ALP ≥2 × ULN at Visit 1
- Unexplained CK concentration >5 × ULN or CK elevation due to known muscle disease (eg, polymyositis, mitochondrial dysfunction) at Visit 1
- Subjects who have previously received K-877 or CSG452 within 26 weeks of randomization
- Current or past history of illicit drug use within 1 year of Visit 1
- Any condition or therapy, which, in the opinion of the Investigator, might pose a risk to the subject or make participation in the study not in the best interest of the subject
- Special or vulnerable status (eg institutionalized, or person related to or an employee of the sponsor, or investigator)
- Subjects listed for liver transplantation, or a history of liver transplantation
- Unlikely to have noncirrhotic NASH with liver fibrosis based on Visit 1 or historical (performed within 12 weeks prior to Visit 1) FibroScan and Visit 1 AST. FibroScan assessment at Visit 1 can be repeated once if the first attempt failed due to technical reasons.
- Initiation of, or change in, current doses of thiazolidinediones, agents with GLP-1 receptor agonist activity, or vitamin E within 26 weeks of randomization
- Current or planned use of fibrates, agents with potent selective peroxisome proliferator-activated receptor alpha (PPARα) agonist activity, or sodium glucose co transporter 2 (SGLT2) inhibitors, or subjects who have previously received K-877 or CSG452 within 26 weeks of randomization
- Subjects with type 1 diabetes mellitus
- Subjects with poorly controlled T2DM as defined by HbA1c >9% at Visit 1
- Subjects with a prior history of VTE, including PE and DVT, or a confirmed diagnosis of a hypercoagulable state
The study team makes the final eligibility decision.
Where it's taking place
- Japan
- Canada
- United States
- Argentina
- Brazil
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Japan; Canada; United States; Argentina; Brazil. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.