Study to Evaluate the Efficacy and Safety of CC-90001 in Participants With Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis
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| ClinicalTrials.gov Identifier: NCT04048876 |
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Recruitment Status :
Terminated
(Business objectives have changed)
First Posted : August 7, 2019
Results First Posted : June 7, 2023
Last Update Posted : June 7, 2023
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This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, multinational, dose-finding study evaluating the efficacy of three treatment doses of CC-90001 compared with placebo, in Non-alcoholic Steatohepatitis (NASH) participants with Stage 2, Stage 3 liver fibrosis.
This study is designed to assess response to treatment on measures of fibrosis and other efficacy parameters. It will also assess dose response and overall safety.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-alcoholic Fatty Liver Disease Liver Cirrhosis | Drug: CC-90001 Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 56 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Finding Study To Evaluate The Efficacy and Safety Of CC-90001 In Subjects With Non-Alcoholic Steatohepatitis (NASH) and Liver Fibrosis |
| Actual Study Start Date : | August 14, 2019 |
| Actual Primary Completion Date : | September 28, 2021 |
| Actual Study Completion Date : | September 28, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: CC-90001 400 mg once daily (QD)
CC-90001 400 mg QD
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Drug: CC-90001
oral |
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Experimental: CC-90001 200 mg once daily
CC-90001 200 mg QD
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Drug: CC-90001
oral |
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Experimental: CC-90001 100 mg once daily
CC-90001 100 mg QD
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Drug: CC-90001
oral |
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Placebo Comparator: Placebo once daily
Placebo QD
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Drug: Placebo
oral |
- Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52 [ Time Frame: From baseline up to week 52 ]
Percentage of participants who achieve a ≥1 stage improvement in liver fibrosis using the NASH CRN Histological Scoring System at Week 52. A participant with a change of ≤ -1 from baseline in fibrosis stage is considered as an improvement responder for this endpoint.
The NASH CRN Histologic Scoring System comprised:
steatosis (0 to 3) lobular inflammation (0 to 3) hepatocellular ballooning (0 to 2) fibrosis disease stage (0 to 4)
- Stage 0 - None;
- Stage 1a - Mild (delicate) zone 3 perisinusoidal fibrosis;
- Stage 1b - Moderate (dense) zone 3 perisinusoidal fibrosis;
- Stage 1c - Portal/periportal fibrosis only;
- Stage 2 - Zone 3 perisinusoidal fibrosis with portal/periportal fibrosis;
- Stage 3 - Bridging fibrosis;
- Stage 4 - Cirrhosis.
- Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52 [ Time Frame: From baseline up to week 52 ]
Percentage of participants with no worsening of steatohepatitis and ≥1 stage improvement in liver fibrosis score at week 52 using the NASH CRN Histological Scoring System at Week 52. A participant with a change of ≥ -1 from baseline in fibrosis stage and no worsening in steatohepatitis is considered as an improvement responder for this endpoint.
The NASH CRN Histologic Scoring System comprised:
steatosis (0 to 3) lobular inflammation (0 to 3) hepatocellular ballooning (0 to 2) fibrosis disease stage (0 to 4)
- Stage 0 - None;
- Stage 1a - Mild (delicate) zone 3 perisinusoidal fibrosis;
- Stage 1b - Moderate (dense) zone 3 perisinusoidal fibrosis;
- Stage 1c - Portal/periportal fibrosis only;
- Stage 2 - Zone 3 perisinusoidal fibrosis with portal/periportal fibrosis;
- Stage 3 - Bridging fibrosis;
- Stage 4 - Cirrhosis.
- Percentage of Participants With Improvement in Total NAS [ Time Frame: From baseline up to week 52 ]Percentage of participants with an improvement of ≥ 2 points in the total NAS with improvement in more than one category of steatosis, lobular inflammation, and hepatocellular ballooning, and no worsening of liver fibrosis at Week 52. A participant with a change of ≤ -2 from baseline in total NAS, a change of ≤ -1 from baseline in more than one subscore, and a change of ≤ 0 from baseline in fibrosis stage is considered as a responder for this endpoint.
- Percentage of Participants With Resolution of NASH [ Time Frame: From baseline up to week 52 ]
Percentage of participants who demonstrate absence of ballooning, and lobular inflammation score of 0 or 1 at Week 52.
Absence of ballooning is defined as a score of 0 in hepatocellular ballooning. A participant with a score of 0 in ballooning, a score of 0 or 1 in lobular inflammation is considered as a responder for this endpoint.
- Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis [ Time Frame: From baseline up to week 52 ]
Percentage of participants who demonstrate absence of ballooning, and lobular inflammation score of 0 or 1 and no worsening of liver fibrosis at Week 52
Absence of ballooning is defined as a score of 0 in hepatocellular ballooning. Worsening of fibrosis stage was defined as progression of NASH CRN fibrosis stage. A participant with a score of 0 in ballooning, a score of 0 or 1 in lobular inflammation, and a change of ≤ 0 from baseline in fibrosis stage is considered as a responder for this endpoint.
- Percentage of Participants Who Progressed to Cirrhosis [ Time Frame: From baseline up to week 52 ]Percentage of participants who progressed to cirrhosis
- Mean Change From Baseline in Liver Biochemistry [ Time Frame: From baseline up to week 52 ]Mean change from Baseline in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT)
- Mean Change From Baseline in Metabolic Parameters [ Time Frame: From baseline up to week 52 ]Mean change from baseline in total low density cholesterol (LDL) high density cholesterol (HDL), and triglycerides
- Cmax [ Time Frame: Day 1 and at Week 4 ]Cmax is defined as maximum plasma concentration of the drug
- Tmax [ Time Frame: Day 1 and at Week 4 ]Tmax is defined is the time to maximum plasma concentration
- AUC (0-t) [ Time Frame: Day 1 and at Week 4 ]Area under the plasma concentration time-curve. AUC from time 0 to the last time of quantifiable concentration
- AUC t [ Time Frame: Day 1 and at Week 4 ]Area under the plasma concentration time-curve. AUC over the dosing interval.
- Apparent Total Body Clearance of the Drug [ Time Frame: At Week 4 ]Apparent total body clearance of the drug (CL/F)
- Number of Participants With Treatment Related Safety Events [ Time Frame: From baseline up to week 52 ]Number of participants with treatment related safety events
- Mean Change From Baseline of ECG Results - PR Intervals [ Time Frame: From baseline up to week 52 ]
Mean change from baseline in PR interval
PR Interval: Atrial depolarization and conduction through the AV node Normal Range: 0.12 - 0.20 (120 to 200 msec)
- Mean Change From Baseline of ECG Results - QRS Duration [ Time Frame: From baseline up to week 52 ]Mean change from baseline in QRS duration QRS Duration: Ventricular depolarization and atrial repolarization Normal Range: 0.08 to 0.10 (80 to 100 msec)
- Mean Change From Baseline of ECG Results - QT Interval [ Time Frame: From baseline up to week 52 ]
Mean change from baseline in QT interval
QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec
- Mean Change From Baseline of ECG Results - QTcB Interval [ Time Frame: From baseline up to week 52 ]
Mean change from baseline in QTcB interval
QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec
QTc: QT interval corrected based on the patient's heart rate
QTcB: An electrocardiographic finding in which the QT interval corrected for heart rate using Bazzett's formula. QTc = QT/√(RR) RR= Respiration Rate
- Mean Change From Baseline of ECG Results - QTcF Interval [ Time Frame: From baseline up to week 52 ]
Mean change from baseline in QTcF interval
QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec
QTc: QT interval corrected based on the patient's heart rate
QTcF: An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula. QTc = QT/∛(RR) RR = Respiration rate
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Key Inclusion Criteria Diagnosis of non-alcoholic steatohepatitis (NASH) with presence of Stage 2, Stage 3 fibrosis based of the non-alcoholic steatohepatitis (NASH) Clinical Research Network (CRN) Histologic Scoring System and a nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) of 4 or higher
Exclusion Criteria:
- Key Exclusion Criteria
- History or evidence of decompensated liver disease,
- Hepatitis and fibrosis more likely related to etiologies other than non-alcoholic steatohepatitis (NASH).
- Participant has urine ethyl glucuronide (EtG) > 500 ng/mL at Screening.
- History or positive screen for human immunodeficiency virus (HIV) infection or congenital or human immunodeficiency virus (HIV)-unrelated acquired immunodeficiencies (eg, common variable immunodeficiency [CVID]).
- History of hepatitis B and/or hepatitis C.
- History of malignancy within the last 5 years (exceptions: excised and cured basal/squamous cell skin carcinomas and cervical carcinoma in situ).
- Pregnancy or lactation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04048876
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| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
| Responsible Party: | Celgene |
| ClinicalTrials.gov Identifier: | NCT04048876 |
| Other Study ID Numbers: |
CC-90001-NASH-001 U1111-1235-3234 ( Other Identifier: WHO ) 2018-004431-79 ( EudraCT Number ) |
| First Posted: | August 7, 2019 Key Record Dates |
| Results First Posted: | June 7, 2023 |
| Last Update Posted: | June 7, 2023 |
| Last Verified: | June 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/ |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) Analytic Code |
| Time Frame: | See Plan Description |
| Access Criteria: | See Plan Description |
| URL: | https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Non-Alcoholic Steatohepatitis NASH Non-Alcoholic Fatty Liver Liver Fibrosis CC-90001 |
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Liver Diseases Fatty Liver Liver Cirrhosis Non-alcoholic Fatty Liver Disease |
Fibrosis Pathologic Processes Digestive System Diseases |