Phase 2b Study of MK-3655 in Individuals with Pre cirrhotic Nonalcoholic Steatohepatitis (NASH)

Phase 1

• Conditions: MedDRA version: 24.1Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2019-003048-63-DE
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-04
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 328

Inclusion Criteria

1. Has histological confirmation of NASH based on 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 female aged 18 years to 80 years (in Japan and Taiwan, 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 =9.5% 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 1/Screening OR blood pressure is
considered likely to be below these limits by Visit 5/Randomization (Day
1) with initiation or adjustment of antihypertensive medication.
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. A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
Is not a WOCBP
OR
Is a WOCBP and:
- Uses a contraceptive method that is highly effective.
- Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Abstains from breastfeeding during the study intervention period and at least 16 weeks after the last dose of study intervention.
-Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy.
12. The participant (or legally acceptable representative, if applicable)
has provided documented 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

Exclusion Criteria

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 (cholangitis)
- Primary sclerosing cholangitis
- Reye Syndrome
- Splenomegaly
- Wilson's disease
- Documented Cushing disease, Cushing syndrome, or any condition
associated with hypercortisolism
- Hyperthyroidism, and is currently being treated.
- Hypothyroidism, and is on thyroid hormone replacement therapy that
has not been at a stable dose for at least 12 weeks prior to Visit
1/Screening.
- 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 been treated with the following agents:
Within =12 months before Visit 1/Screening:
-Thiazolidinediones (ie, pioglitazone, rosiglitazone)
-Investigational agents as defined in the protocol
Within =6 months before Visit 1/Screening:
-L-ornithine L-aspartate
18. Is on treatment with or has used bone-active agents in the classes listed in the protocol =24 months before Visit 1/Screening.
19. Is on treatment with or has used drugs associate

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified