Study to Evaluate the Efficacy and Safety of CC-90001 in Participants With Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis

Phase 2

Terminated

• Conditions: Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
• Interventions: Drug: CC-90001; Drug: Placebo

• Registration Number: NCT04048876
• Lead Sponsor: Celgene

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-07-17
• Study First Submitted QC: 2019-08-06
• Study First Posted: 2019-08-07
• Study Start: 2019-08-14
• Primary Completion: 2021-09-28
• Study Completion: 2021-09-28
• Results First Submitted: 2022-09-28
• Status Verified: 2023-06
• Results First Submitted QC: 2023-06-06
• Last Update Submitted: 2023-06-06
• Results First Posted: 2023-06-07
• Last Update Posted: 2023-06-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 56

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

1. History or evidence of decompensated liver disease,
2. Hepatitis and fibrosis more likely related to etiologies other than non-alcoholic steatohepatitis (NASH).
3. Participant has urine ethyl glucuronide (EtG) > 500 ng/mL at Screening.
4. 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]).
5. History of hepatitis B and/or hepatitis C.
6. History of malignancy within the last 5 years (exceptions: excised and cured basal/squamous cell skin carcinomas and cervical carcinoma in situ).
7. Pregnancy or lactation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CC-90001 200 mg once daily	CC-90001	CC-90001 200 mg QD
Placebo once daily	Placebo	Placebo QD
CC-90001 400 mg once daily (QD)	CC-90001	CC-90001 400 mg QD
CC-90001 100 mg once daily	CC-90001	CC-90001 100 mg QD

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52	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.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline of ECG Results - QTcB Interval	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
Percentage of Participants With Resolution of NASH	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.
Tmax	Day 1 and at Week 4	Tmax is defined is the time to maximum plasma concentration
Mean Change From Baseline of ECG Results - PR Intervals	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)
Percentage of Participants Who Progressed to Cirrhosis	From baseline up to week 52	Percentage of participants who progressed to cirrhosis
Cmax	Day 1 and at Week 4	Cmax is defined as maximum plasma concentration of the drug
AUC t	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	At Week 4	Apparent total body clearance of the drug (CL/F)
Mean Change From Baseline of ECG Results - QRS Duration	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)
Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52	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	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.
Mean Change From Baseline in Liver Biochemistry	From baseline up to week 52	Mean change from Baseline in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT)
AUC (0-t)	Day 1 and at Week 4	Area under the plasma concentration time-curve. AUC from time 0 to the last time of quantifiable concentration
Number of Participants With Treatment Related Safety Events	From baseline up to week 52	Number of participants with treatment related safety events
Mean Change From Baseline of ECG Results - QT Interval	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 - QTcF Interval	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
Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis	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.
Mean Change From Baseline in Metabolic Parameters	From baseline up to week 52	Mean change from baseline in total low density cholesterol (LDL) high density cholesterol (HDL), and triglycerides

Trial Locations

Locations (142)

Saint Joseph's Hosptial and Medical Center - Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic Phoenix; 🇺🇸 Phoenix, Arizona, United States

UC San Diego School of Medicine; 🇺🇸 La Jolla, California, United States

Cedars-Sinai Comprehensive Transplant Center; 🇺🇸 Los Angeles, California, United States

California Liver Research Institute; 🇺🇸 Pasadena, California, United States

Inland Empire Liver Foundation; 🇺🇸 Rialto, California, United States

University of California Davis Medical Center; 🇺🇸 Sacramento, California, United States

Southern California GI & Liver Centers; 🇺🇸 San Clemente, California, United States

University of Colorado, School of Medicine - Hepatology Clinic - Anschutz; 🇺🇸 Aurora, Colorado, United States

Peak Gastroenterology Associates; 🇺🇸 Colorado Springs, Colorado, United States

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