Comparison of colestimide /elovixibat combination therapy versus colestimide /placebo combintion in NASH patients with dyslipidemia: a multicenter, double-blind, randomized controlled study(NECST)

JRCT ID: jRCTs031200144

Registered date:12/10/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: NASH with dyslipidemia
• Date of first enrollment: 12/10/2020
• Target sample size: 40
• Study type: Interventional

Intervention(s)

Goup A: Arm Colestimide + placebo
Colestimide1.5g and two placebo tablets are orally administered once a day for 48 weeks.

Group B: Arm Colestimide+ erobixibat administration
Oral administration of colestimide1.5g and erobixibat 5mg tablets (total 10mg) once a day for 48 weeks.

Outcome(s)

• Primary Outcome: Absoiute change from baseline in ALT at Week 48

Secondary Outcome

1. Improvement of fibrosis with no worsening of NASH
2. Resolution of NASH with no worsening of fibrosis
3. Improvement of fibrosis by >=1 stage or resolution of NASH without worsening of either
4. No worsening of fibrosis and no worsening of NASH
5. Improvement of NAS by >=2 with no worsening of fibrosis
6. Improvement of fibrosis and resolution of NASH as a composite endpoint
7. Improvement in fibrosis by >=2 stages
8. Resolution of fibrosis
9. >=1-point improvement in steatosis
10.>=1-point improvement in lobular inflammation
11. >=1-point improvement in hepatocellular ballooning
12. Change of MRE
13. Change of MRI-PDFF
14. Change of parameters in blood tests (AST, gamma-GTP, ALP, total bilirubin, total cholesterol, LDL cholesterol, triglyceride, HDL cholesterol, HbA1c), BMI, and body weight
15.The Change in ALT at week 48
16. Change from Baseline in Risk of Cardiovascular Events (10 Year ASCVD Risk Score) at 48 Weeks of Treatment
17. Incidence of Adverse Events

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

1) Patients between the ages of 20 and 85 years old at the time of obtaining consent
2) Patients whose liver biopsy within 16 weeks prior to enrollment meet the following
Fibrosis stage F1 to F3 and NAFLD activity score (NAS) of 4 or more (1 point or more for each category) on the NASH Clinical Research Network (CRN) criteria
1. steatosis (0-3 points)
2. ballooning (0-2 points)
3. lobular inflammation (0-3 points)
3) Patients who meet either (1) or (2) below within 12 weeks prior to enrollment
(1) Patients who meet any of the following values
1. Triglycerides (TG)150 mg/dL
2. HDL cholesterol (HDL-C)<40 mg/dL
3. LDL cholesterol (LDL-C)>=120 mg/dL
(2) Patients diagnosed with dyslipidemia and undergoing drug treatment
4) Patients whose written consent to participate in the study has been obtained
5) Patients with a stable diet and physical activity during the study

At allocation Dose initiation criteria
1) Patients whose liver biopsy within 16 weeks prior to enrollment meet the following
Fibrosis stage F1 to F3 and NAFLD activity score (NAS) of 4 or more (1 point or more for each category) on the NASH Clinical Research Network (CRN) criteria
1. steatosis (0-3 points)
2. ballooning (0-2 points)
3. lobular inflammation (0-3 points)
2) ALT greater than 43 IU/L for males and 24 IU/L for females within 12 weeks prior to the start of treatment
3) ALT=<300IU/L or AST=<300IU/L within 12 weeks prior to the start of treatment
4) Body mass index (BMI)>=22 kg/m2 within 12 weeks prior to the start of treatment
5) Patients with no weight change of 10% or more within 12 weeks before the start of administration
6) Patients with total bilirubin=<3.0 mg/dl within 12 weeks prior to the start of treatment ( except for Gilberts syndrome)
7) In case the patient had been taking SGLT2 inhibitors, GLP-1 agonists, thiazolidinediones, or vitamin E within 24 weeks prior to the start of treatment, the patient must be on the same drug and at the same dose.(Patients who have started, discontinued, changed drugs, or changed doses are not eligible.)

Exclude criteria

1) Patients with a evidence of acute or chronic liver disease other than NASH
(1) Hepatitis B (excluding past infection) or C (excluding post-SVR)
(2) Patients with autoimmune hepatitis
(3) Patients with primary cholangitis, primary sclerosing cholangitis, Wilson's disease, alpha1-antitrypsin deficiency, hemochromatosis or iron overload, drug or alcoholic liver disease, or bile duct obstruction.
(4) Patients with suspected or confirmed diagnosis of hepatocellular carcinoma
2) Patients with an average alcohol intake of 30 g of ethanol equivalent per day or more for males and 20 g or more for females (more than 12 weeks) in the year before consent was obtained.
3) Patients who are pregnant, lactating, women of childbearing potential, or who cannot consent to use contraception while participating in the study.
4) Patients with concomitant malignancies; Patients who have undergone radical surgery or completed chemotherapy are eligible for enrollment.
5) Patients with liver cirrhosis
6) Patients with findings of portal hypertension (platelets <80,000/uL, varices, ascites, hepatic encephalopathy, splenomegaly)
7) Patients who changed the dose of SGLT2 inhibitor, GLP-1 agonist, thiazolidine or vitamin E within 24 weeks prior to enrollment.
8) Patients on insulin therapy
9) Patients with a history of drug abuse
10) Patients with serious renal or cardiac disease
11) Patients with a history of allergy to this study drug
12) Patients who participate in another clinical research within 4 weeks prior to participation in this study, except for observational studies.
13) Other patients who are deemed inappropriate for this study by the investigators

Related Information

• Primary Sponsor: Kobayashi Takashi
• Source(s) of Monetary Support: Yokohama City University