Phase 2b Study of MK-3655 in Individuals with Pre cirrhotic Nonalcoholic Steatohepatitis (NASH)
- Conditions
- MedDRA version: 22.0Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2019-003048-63-FR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 328
1. Has histological confirmation of NASH based upon a liver biopsy obtained =6 months before Visit 1/Screening. If no acceptable biopsy performed =6 months before Visit 1/Screening is available, a liver biopsy will be performed at Visit 3/Liver Biopsy.
Histological criteria for study entry include:
- NAS =4 with a score =1 point in each component (steatosis, ballooning, and lobular inflammation),
AND
- NASH CRN fibrosis score of Stage 2 or 3.
2. Has an MRI-PDFF =8% as assessed at Visit 2/MRI-PDFF.
3. Has a baseline MELD-Na score =12 at Visit 1/Screening.
4. Is a male or a postmenopausal female aged 18 years to 80 years (in Japan, aged 20 to 80 years), at the time of signing the ICF.
5. Has a BMI =25 kg/m2 and =50 kg/m2 at the time of Visit 1/Screening.
6. Has stable weight (based on self-reporting) defined as =5% gain or loss of body weight for at least 3 months before Visit 1/Screening.
7. Meets one of the following criteria:
- Has no history of T2DM.
OR
- Has a history of T2DM with an A1C =9.0% at Visit 1/Screening and controlled by diet or stable doses of AHAs.
8. Has a systolic blood pressure of =160 mm Hg and a diastolic blood pressure =90 mm Hg (after at least a 10-minute seated rest) based on the mean of 3 measurements at Visit 5/Randomization.
9. Be willing and able to comply with scheduled visits, treatment plan, laboratory tests,and/or other study procedures.
10. Contraceptive use by male participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
11. Is a postmenopausal female.
12. The participant (or legally acceptable representative, if applicable) provides written informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the main study without participating in FBR.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 230
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 98
1. Has presence of cirrhosis on liver biopsy.
2. Has Type 1 diabetes.
3. Has a history of malignancy, unless cancer free =5 years, or is under evaluation for active or suspected malignancy before signing the ICF except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
4. Has a history of bariatric surgery =5 years before Visit 1/Screening.
5. Has undergone a major surgical procedure =3 months before signing the ICF or has major surgery planned during the study.
6. Has a history or evidence of:
- Chronic liver disease other than NASH
- Hepatitis B as defined by the presence of HBsAg
- Hepatitis C as defined by the presence of HCV RNA or positive hepatitis C antibody (anti-HCV); participants with a history of HCV infection may be included if HCV PCR is negative =3 years
- Drug-induced liver disease
- Ongoing autoimmune liver disease
- Decompensated liver disease
- HIV
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Reye Syndrome
- Splenomegaly
- Wilson’s disease
- Documented Cushing disease, Cushing syndrome, or any condition associated with hypercortisolism
- Hypothyroidism, hyperthyroidism, or subclinical thyroid disease
- Alpha-1-antitrypsin deficiency
- Hemochromatosis or iron overload
- Spontaneous bacterial peritonitis
- Known bile duct obstruction
- Hepatocellular carcinoma
- Untreated obstructive sleep apnea
- Hemostasis disorder
- Hematological disorder
7. Has significant systemic or major illnesses other than liver disease, including recent events (=6 months before Visit 1/Screening) of congestive heart failure, unstable coronary artery disease, arterial revascularization, pulmonary disease, renal failure, stroke, transient ischemic attack, or organ transplantation.
8. Has a known hypersensitivity to any of the ingredients or excipients of the IMP.
9. Has experienced any bone trauma, fracture, or bone surgery =2 months before Visit 1/Screening.
10. Has a history of osteoporosis or an indication that requires treatment with a bone-active pharmacological agent in the classes listed in exclusion criterion #18 at Visit 1/Screening.
11. Has current or history of significant alcohol consumption for a period of more than 3 consecutive months =24 months before Visit 1/Screening.
12. Has an inability to reliably quantify alcohol consumption.
13. Has a recent history of drug abuse (defined as =3 years) or is a current user of recreational or illicit drugs at the time of Visit 1/Screening.
14. Has a known psychiatric or any other cognitive disorder per the opinion of the investigator, that would interfere with the participant’s ability to cooperate with the requirements of the study.
15. Is at imminent risk of self-harm, based on clinical interview and responses on the C-SSRS, or of harm to others in the opinion of the investigator.
16. Has a total score >12 on the PHQ-9.
17. Is on treatment with or has used the following agents =24 months before Visit 1/Screening:
- Thiazolidinediones
- Fibric acid derivatives
- Obeticholic acid
- High dose vitamin E (>400 IU/day)
- L-ornithine L-aspartate
18. Is on treatment with or has used bone-active agents in the classes listed below =24 months before Visit 1/Screening.
- Bisphosphonates
- Calcitonin
- Selective estrogen receptor modulator (estrogen receptor agonist/antagonist)
- PTH and PTH analogs
- RANK ligand inhibitor
- Anti-sclerostin antibody
- Aromatase inhibitors
- GnRH agonists
19. Is on treatment with or has used drugs assoc
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method