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-FR
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- 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 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’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, gemfibrozil, metformin, sodium-glucose co-transporter 2 (SGLT2) inhibitors (eg, canagliflozin), dipeptidyl peptidase-4 inhibitors (‘gliptins’) (such as sitagliptin), glucagon peptide-1 agonists (eg, liraglutide [1.2 mg or 1.8 mg QD] for indications other than weight loss).
7. If receiving thiazolidinediones (eg, pioglitazone), the doses must have been stable with 6 months prior to Screening.
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 study treatment. This applies even if the subject practices true abstinence* from heterosexual contact.
b.Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use two forms of effective birth control methods (for example: birth control pills, condoms, etc.) (one of which is highly effective)at the same time, and be able to comply with, effective contraception without interruption, 28 days prior to starting IP, during the study therapy (including dose interruptions), and for 28 days after discontinuation of IP.
Approved options for birth control are:
•Any one of the following highly effective methods: Hormonal contraception (for example, birth control pills, intravaginal ring, transdermal patch, injection, implant); intrauterine device (IUD); tubal ligation (tying your tubes); or a partner with a vasectomy. Note: Certain drugs may reduce the effectiveness of hormonal contraceptives during and up to one month after discontinuation of these concomitant therapies.
•Any effective method, for example, condoms.
9. Male
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 biliary cholangitis, Wilson's disease, alpha-1-antitrypsin deficiency, hemochromatosis or iron overload, drug-induced liver disease
4.Hemoglobin A1c (HbA1c)>8% at Screening
5.Subjects with evidence of worsening liver function based on two liver function tests during Screening period (refer Section 6.1)
6.Subject with a QTcF >450msec
7.Subject is likely to have liver transplantation or bariatric surgery 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 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
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 study for these subjects. Documentation of adequate treatment for TB must be obtained prior to randomization
15.Subject has had a household contact with a person with active TB and subject did not receive appropriate and documented prophylaxis for TB.Note: Household contact is a person who shared the same enclosed living space as the index case for one or more nights or for frequent or extended daytime pe
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