STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CC-90001 IN SUBJECTS WITH NONALCOHOLIC STEATOHEPATITIS (NASH) AND STAGE 3 OR STAGE 4 LIVER FIBROSIS
- Conditions
- Confirmed diagnosis of NASH and Stage 3 or Stage 4 fibrosis based upon the NASH Clinical Research Network (CRN) Histologic Scoring System and a nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) of 4 or higher, with a score of at least 1 for each of the three components (steatosis, hepatocellular ballooning, and lobular inflammation).Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2018-004431-79-GB
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 300
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is male or female = 18 years of age at the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of NASH with presence of Stage2, Stage 3 or Stage 4 fibrosis based upon central reading of the NASH CRN Histologic Scoring System and a NAFLD Activity Score (NAS) of 4 or higher, with a score of at least 1 for each of the three components (steatosis scored 0 to 3, ballooning degeneration scored 0 to 2, and lobular inflammation scored 0 to 3) within 6 months of Screening. Note: Subjects who do not have pathological specimens from a prior liver biopsy obtained within 6 months of Screening and available for central reading, must undergo liver biopsy during Screening. Appendix B and Appendix C outline an algorithm to help determine which potential subjects may proceed to liver biopsy.
5. If histopathological specimens are submitted from a historical liver biopsy, the subject could not be on a therapy specifically for the treatment of NASH after liver biopsy and the subject’s weight must have been documented to be stable since the liver biopsy (eg, within 5% if the liver biopsy was obtained 4 to 6 months prior to Screening or within 2.5% if the liver biopsy was obtained less than 4 months prior to Screening).
6. If receiving any of the following agents, the doses must have been stable within 3 months prior to Screening and the subject agrees to maintain stable doses during the course of the study, unless required to adjust doses due to safety reasons: vitamin E, ursodeoxycholic acid, fibric acid derivatives (fibrates) (eg gemfibrozil) metformin, sodium-glucose co-transporter 2 (SGLT2) inhibitors (eg, canagliflozin), dipeptidyl peptidase-4 inhibitors (‘gliptins’) (such as sitagliptin), glucagon peptide-1 agonists (GLP-1) (eg, liraglutide [1.2 mg or 1.8 mg QD] for indications other than weight loss). Note: If historical liver biopsy is submitted, the doses of above medications must have been stable for 3 months prior to biopsy and stable doses should be maintained through screening and during the course of the study. If SGLT2 inhibitors and GLP-1 agonists have been recently discontinued, the treatment must have been stopped for at least 3 months prior to screening or historical biopsy used for screening assessment.
7. If receiving thiazolidinediones (eg, pioglitazone), or vitamin E, the doses must have been stable for 3 months prior to Screening and the subject must agree to maintain stable doses throughout the course of the study. Note: If historical liver biopsy is submitted the doses of above medications must have been stable for 3 months prior to biopsy and stable doses should be maintained through screening and during the course of the study. If thiazolidinediones (eg, pioglitazone) or vitamin E have been recently discontinued, the treatment must have been stopped for at least 3months prior to Screening or historical biopsy used for Screening assessment.
8. Females of childbearing potential (FCBP) must:
a.Have two negative pregnancy tests as verified by the Investigator prior to starting investigational product (IP). She must agree to ongoing pregnancy testing during the course of the study, and after end of stud
1.Subject has any significant medical condition, laboratory abnormality (other than NASH related dyscrasias), or psychiatric illness or place the subject at unacceptable risk if he/she were to participate in the study
2. History or evidence of decompensated liver disease, including clinical ascites, hepatic encephalopathy, or variceal bleeding
3.Hepatitis and fibrosis more likely related to etiologies other than NASH such as, but not limited to, alcoholic steatohepatitis, autoimmune hepatitis, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, primary biliary cirrhosis, primary biliarysclerosing cholangitis, Wilson's disease, alpha-1-antitrypsin deficiency, hemochromatosis or iron overload, drug-induced liver disease
4.Haemoglobin A1c (HbA1c)>9.5% at Screening
5.Subject with evidence of worsening liver function based on two measurement of AST, ALT, alkaline phosphatase (ALP) and total bilirubin tests (TBL) during Screening period (refer Section 6.1)
6.Subject with a QTcF >450msec
7.Subject is likely to have liver transplantation or subject is likely to have liver transplantation during the study
8. Current or history of recreational drug abuse or significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening. Significant alcohol consumption is defined as more than 14 oz (420mL) per wk in females and more than 21 oz (630 mL) per wk in males, on average (1 oz/30mL of alcohol is present in one 12 oz/360mL beer, one 4 oz/120mL glass of wine, and a 1 oz/30mL measure of 40% proof alcohol).
9.Subject has urine ethyl glucuronide(EtG)>500ng/mL at Screening
10.Use of any drugs historically associated with nonalcoholic fatty liver disease (NAFLD) for more than 2 consecutive wks within a year prior to randomization or any drugs that are known to cause hepatotoxicity, such as, but not limited to, acetaminophen at dosages of >3grams/day and niacin at dosages of >2grams/day within 2 wks of randomization
11.Receiving any biologic agents, or cytokine inhibitors within 3 months of Screening
12.Use of approved weight-loss medications within 3 months of Screening
13. Active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including, but not limited to, atypical mycobacterial disease and herpes zoster), or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 wks of Screening Visit and at any time during the Screening Phase, up through the first dose of IP. Additionally, in the case of prior SARS-CoV-2 infection, symptoms must have completely resolved and based on investigator assessment in consultation with the clinical trial physician, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment.
14.History of active or latent or active tuberculosis (TB), unless there is medical record documentation of successful completion of a standard course of treatment considered appropriate, based on local prevalence of multi-drug resistant TB and consistent with WHO guidelines.Note: If a subject has adequate documentation of successful treatment for either latent or active TB, the QuantiFERON-TB Gold test is not needed. Instead, a chest radiograph, obtained within the 12 wks prior to Screening, without changes suggestive of active TB infection as determined by a qualified radiologist, will be sufficient to permit further participation in the stud
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