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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
56
Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at 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.
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
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.
Time frame: From baseline up to week 52
Percentage of Participants With Improvement in Total NAS
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.
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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
...and 132 more locations
Time frame: From baseline up to week 52
Percentage of Participants With Resolution of NASH
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.
Time frame: From baseline up to week 52
Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis
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.
Time frame: From baseline up to week 52
Percentage of Participants Who Progressed to Cirrhosis
Percentage of participants who progressed to cirrhosis
Time frame: From baseline up to week 52
Mean Change From Baseline in Liver Biochemistry
Mean change from Baseline in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT)
Time frame: From baseline up to week 52
Mean Change From Baseline in Metabolic Parameters
Mean change from baseline in total low density cholesterol (LDL) high density cholesterol (HDL), and triglycerides
Time frame: From baseline up to week 52
Cmax
Cmax is defined as maximum plasma concentration of the drug
Time frame: Day 1 and at Week 4
Tmax
Tmax is defined is the time to maximum plasma concentration
Time frame: Day 1 and at Week 4
AUC (0-t)
Area under the plasma concentration time-curve. AUC from time 0 to the last time of quantifiable concentration
Time frame: Day 1 and at Week 4
AUC t
Area under the plasma concentration time-curve. AUC over the dosing interval.
Time frame: Day 1 and at Week 4
Apparent Total Body Clearance of the Drug
Apparent total body clearance of the drug (CL/F)
Time frame: At Week 4
Number of Participants With Treatment Related Safety Events
Number of participants with treatment related safety events
Time frame: From baseline up to week 52
Mean Change From Baseline of ECG Results - PR Intervals
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)
Time frame: From baseline up to week 52
Mean Change From Baseline of ECG Results - QRS Duration
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)
Time frame: From baseline up to week 52
Mean Change From Baseline of ECG Results - QT Interval
Mean change from baseline in QT interval QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec
Time frame: From baseline up to week 52
Mean Change From Baseline of ECG Results - QTcB Interval
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
Time frame: From baseline up to week 52
Mean Change From Baseline of ECG Results - QTcF Interval
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
Time frame: From baseline up to week 52