Liver Cirrhosis, Non-alcoholic Fatty Liver Disease
Conditions
Keywords
Non-Alcoholic Steatohepatitis, NASH, Non-Alcoholic Fatty Liver, Liver Fibrosis, CC-90001
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.
Interventions
DRUGCC-90001
oral
DRUGPlacebo
oral
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Percentage of Participants Who Progressed to Cirrhosis | From baseline up to week 52 | Percentage of participants who progressed to cirrhosis |
| 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) |
| 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 |
| Cmax | Day 1 and at Week 4 | Cmax is defined as maximum plasma concentration of the drug |
| Tmax | Day 1 and at Week 4 | Tmax is defined is the time to maximum plasma concentration |
| 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. |
| 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) |
| 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 - 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) |
| 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) |
| 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 - 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 |
| 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 |
| 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 |
Countries
Australia, Canada, France, Germany, Japan, Poland, South Korea, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CC-90001 100mg CC-90001 100 mg PO QD | 13 |
| CC-90001 200mg CC-90001 200 mg PO QD | 15 |
| CC-90001 400mg CC-90001 400 mg PO QD | 13 |
| Placebo Placebo in placebo controlled phase. CC-90001 100mg, 200mg or 400mg in active treatment extension phase | 15 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Active Treatment Phase | Study Terminated by Sponsor | 2 | 0 | 3 | 2 |
| Placebo Controlled Phase | Adverse Event | 0 | 1 | 0 | 0 |
| Placebo Controlled Phase | Study Terminated by Sponsor | 10 | 12 | 10 | 12 |
| Placebo Controlled Phase | Withdrawal by Subject | 1 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | CC-90001 100mg | CC-90001 200mg | CC-90001 400mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 52.2 Years STANDARD_DEVIATION 12.37 | 58.3 Years STANDARD_DEVIATION 9.92 | 52.1 Years STANDARD_DEVIATION 11.91 | 60.5 Years STANDARD_DEVIATION 8.2 | 56.0 Years STANDARD_DEVIATION 10.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 4 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 15 Participants | 9 Participants | 12 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 5 Participants | 1 Participants | 4 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 7 Participants | 9 Participants | 11 Participants | 9 Participants | 36 Participants |
| Sex: Female, Male Female | 8 Participants | 11 Participants | 6 Participants | 12 Participants | 37 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 7 Participants | 3 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 15 | 0 / 13 | 0 / 15 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 10 / 13 | 13 / 15 | 12 / 13 | 10 / 15 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 2 / 13 | 1 / 15 | 2 / 13 | 0 / 15 | 0 / 1 | 0 / 1 |
Outcome results
Primary
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
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC-90001 100mg | Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52 | 15.4 Percentage of Participants |
| CC-90001 200mg | Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52 | 0 Percentage of Participants |
| CC-90001 400mg | Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52 | 7.7 Percentage of Participants |
| Placebo | Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52 | 6.7 Percentage of Participants |
Secondary
Apparent Total Body Clearance of the Drug
Apparent total body clearance of the drug (CL/F)
Time frame: At Week 4
Population: PK evaluable population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CC-90001 100mg | Apparent Total Body Clearance of the Drug | 39.5 L/h |
| CC-90001 400mg | Apparent Total Body Clearance of the Drug | 18.9 L/h |
Secondary
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
Population: PK evaluable population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | AUC (0-t) | Day 1 | 2322.7 h*ng/mL | — |
| CC-90001 100mg | AUC (0-t) | Week 4 | 2530.5 h*ng/mL | — |
| CC-90001 400mg | AUC (0-t) | Day 1 | 26803.9 h*ng/mL | Geometric Coefficient of Variation 62.87 |
| CC-90001 400mg | AUC (0-t) | Week 4 | 20918.8 h*ng/mL | — |
Secondary
AUC t
Area under the plasma concentration time-curve. AUC over the dosing interval.
Time frame: Day 1 and at Week 4
Population: PK evaluable population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | AUC t | Day 1 | 2322.7 h*ng/mL | — |
| CC-90001 100mg | AUC t | Week 4 | 2530.5 h*ng/mL | — |
| CC-90001 400mg | AUC t | Day 1 | 27173.7 h*ng/mL | Geometric Coefficient of Variation 59.71 |
| CC-90001 400mg | AUC t | Week 4 | 21182.1 h*ng/mL | — |
Secondary
Cmax
Cmax is defined as maximum plasma concentration of the drug
Time frame: Day 1 and at Week 4
Population: PK evaluable population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | Cmax | Day 1 | 501.0 ng/mL | — |
| CC-90001 100mg | Cmax | Week 4 | 352.0 ng/mL | — |
| CC-90001 400mg | Cmax | Day 1 | 2938.8 ng/mL | Geometric Coefficient of Variation 44.94 |
| CC-90001 400mg | Cmax | Week 4 | 2610.0 ng/mL | — |
Secondary
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
Population: Full Analysis Set Population at Week 52 with evaluable measures
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | Mean Change From Baseline in Liver Biochemistry | AST (U/L) | 9.5 U/L | Standard Deviation 10.61 |
| CC-90001 100mg | Mean Change From Baseline in Liver Biochemistry | ALT (U/L) | 26.0 U/L | Standard Deviation 19.8 |
| CC-90001 100mg | Mean Change From Baseline in Liver Biochemistry | GGT (U/L) | 13.0 U/L | Standard Deviation 28.28 |
| CC-90001 400mg | Mean Change From Baseline in Liver Biochemistry | AST (U/L) | -17.0 U/L | Standard Deviation 10.15 |
| CC-90001 400mg | Mean Change From Baseline in Liver Biochemistry | ALT (U/L) | -22.3 U/L | Standard Deviation 14.19 |
| CC-90001 400mg | Mean Change From Baseline in Liver Biochemistry | GGT (U/L) | -6.3 U/L | Standard Deviation 5.86 |
| Placebo | Mean Change From Baseline in Liver Biochemistry | ALT (U/L) | -6.5 U/L | Standard Deviation 21.92 |
| Placebo | Mean Change From Baseline in Liver Biochemistry | GGT (U/L) | 2.5 U/L | Standard Deviation 58.69 |
| Placebo | Mean Change From Baseline in Liver Biochemistry | AST (U/L) | 7.0 U/L | Standard Deviation 4.24 |
Secondary
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
Population: Full Analysis Set Population at Week 52 with evaluable measures
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | Mean Change From Baseline in Metabolic Parameters | LDL (mmol/L) | 0.970 mmol/L | Standard Deviation 0.4525 |
| CC-90001 100mg | Mean Change From Baseline in Metabolic Parameters | HDL (mmol/L) | 0.005 mmol/L | Standard Deviation 0.0354 |
| CC-90001 100mg | Mean Change From Baseline in Metabolic Parameters | Triglycerides (mmol/L) | -0.135 mmol/L | Standard Deviation 0.0495 |
| CC-90001 400mg | Mean Change From Baseline in Metabolic Parameters | LDL (mmol/L) | 0.623 mmol/L | Standard Deviation 0.3785 |
| CC-90001 400mg | Mean Change From Baseline in Metabolic Parameters | HDL (mmol/L) | 0.147 mmol/L | Standard Deviation 0.2155 |
| CC-90001 400mg | Mean Change From Baseline in Metabolic Parameters | Triglycerides (mmol/L) | 0.027 mmol/L | Standard Deviation 0.265 |
| Placebo | Mean Change From Baseline in Metabolic Parameters | HDL (mmol/L) | 0.120 mmol/L | Standard Deviation 0.2687 |
| Placebo | Mean Change From Baseline in Metabolic Parameters | Triglycerides (mmol/L) | -0.805 mmol/L | Standard Deviation 0.5445 |
| Placebo | Mean Change From Baseline in Metabolic Parameters | LDL (mmol/L) | -1.395 mmol/L | Standard Deviation 1.3223 |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 12 | 5.7 msec | Standard Deviation 10.32 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 52 | -7.0 msec | Standard Deviation 9.9 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 24 | 4.4 msec | Standard Deviation 7.46 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 4 | 5.8 msec | Standard Deviation 10.42 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 4 | -5.5 msec | Standard Deviation 10.18 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 12 | -2.3 msec | Standard Deviation 10.01 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 24 | -2.8 msec | Standard Deviation 3.9 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 4 | 3.6 msec | Standard Deviation 14.84 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 52 | -7.7 msec | Standard Deviation 27.06 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 24 | -3.7 msec | Standard Deviation 8.99 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - PR Intervals | Week 12 | 2.3 msec | Standard Deviation 21.02 |
| Placebo | Mean Change From Baseline of ECG Results - PR Intervals | Week 52 | 13.5 msec | Standard Deviation 10.61 |
| Placebo | Mean Change From Baseline of ECG Results - PR Intervals | Week 4 | 5.0 msec | Standard Deviation 19.24 |
| Placebo | Mean Change From Baseline of ECG Results - PR Intervals | Week 12 | 15.2 msec | Standard Deviation 26.99 |
| Placebo | Mean Change From Baseline of ECG Results - PR Intervals | Week 24 | 3.2 msec | Standard Deviation 12.75 |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 12 | 4.0 msec | Standard Deviation 3.77 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 52 | -5.5 msec | Standard Deviation 7.78 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 24 | -8.7 msec | Standard Deviation 16.54 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 4 | 0.8 msec | Standard Deviation 2.93 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 4 | 0.1 msec | Standard Deviation 5.79 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 12 | 0.7 msec | Standard Deviation 3.56 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 24 | 0.6 msec | Standard Deviation 4.77 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 4 | -0.1 msec | Standard Deviation 6.9 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 52 | -1.3 msec | Standard Deviation 4.16 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 24 | -2.7 msec | Standard Deviation 3.77 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QRS Duration | Week 12 | -2.5 msec | Standard Deviation 5.38 |
| Placebo | Mean Change From Baseline of ECG Results - QRS Duration | Week 52 | 1.0 msec | Standard Deviation 7.07 |
| Placebo | Mean Change From Baseline of ECG Results - QRS Duration | Week 4 | -1.2 msec | Standard Deviation 3.59 |
| Placebo | Mean Change From Baseline of ECG Results - QRS Duration | Week 12 | -2.8 msec | Standard Deviation 3.11 |
| Placebo | Mean Change From Baseline of ECG Results - QRS Duration | Week 24 | -1.0 msec | Standard Deviation 3.9 |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 12 | -0.3 msec | Standard Deviation 19.75 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 52 | -13.0 msec | Standard Deviation 1.41 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 24 | 7.9 msec | Standard Deviation 10.75 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 4 | -0.8 msec | Standard Deviation 16.18 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 4 | -2.8 msec | Standard Deviation 17.51 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 12 | -1.5 msec | Standard Deviation 10.62 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 24 | 1.2 msec | Standard Deviation 16.41 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 4 | -4.0 msec | Standard Deviation 15.18 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 52 | -35.0 msec | Standard Deviation 9.85 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 24 | 0.7 msec | Standard Deviation 39.65 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QTcB Interval | Week 12 | -9.6 msec | Standard Deviation 22.59 |
| Placebo | Mean Change From Baseline of ECG Results - QTcB Interval | Week 52 | 4.5 msec | Standard Deviation 14.85 |
| Placebo | Mean Change From Baseline of ECG Results - QTcB Interval | Week 4 | -9.3 msec | Standard Deviation 10.81 |
| Placebo | Mean Change From Baseline of ECG Results - QTcB Interval | Week 12 | 1.4 msec | Standard Deviation 9.25 |
| Placebo | Mean Change From Baseline of ECG Results - QTcB Interval | Week 24 | -11.0 msec | Standard Deviation 10.55 |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 12 | 1.0 msec | Standard Deviation 12.33 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 52 | -11.5 msec | Standard Deviation 3.54 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 24 | 9.4 msec | Standard Deviation 8.71 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 4 | -3.9 msec | Standard Deviation 15.33 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 4 | -3.5 msec | Standard Deviation 14.45 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 12 | -4.6 msec | Standard Deviation 6.43 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 24 | -3.0 msec | Standard Deviation 10.49 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 4 | -1.4 msec | Standard Deviation 12.06 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 52 | -27.7 msec | Standard Deviation 7.77 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 24 | -0.9 msec | Standard Deviation 30.17 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QTcF Interval | Week 12 | -6.3 msec | Standard Deviation 21.54 |
| Placebo | Mean Change From Baseline of ECG Results - QTcF Interval | Week 52 | 5.5 msec | Standard Deviation 0.71 |
| Placebo | Mean Change From Baseline of ECG Results - QTcF Interval | Week 4 | -4.0 msec | Standard Deviation 10.53 |
| Placebo | Mean Change From Baseline of ECG Results - QTcF Interval | Week 12 | -1.4 msec | Standard Deviation 11.24 |
| Placebo | Mean Change From Baseline of ECG Results - QTcF Interval | Week 24 | 2.2 msec | Standard Deviation 12.67 |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QT Interval | Week 12 | 10.6 msec | Standard Deviation 24.57 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QT Interval | Week 52 | -6.0 msec | Standard Deviation 8.49 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QT Interval | Week 24 | 12.0 msec | Standard Deviation 11.55 |
| CC-90001 100mg | Mean Change From Baseline of ECG Results - QT Interval | Week 4 | 0.4 msec | Standard Deviation 19.71 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QT Interval | Week 4 | -7.6 msec | Standard Deviation 12.52 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QT Interval | Week 12 | -9.8 msec | Standard Deviation 15.48 |
| CC-90001 200mg | Mean Change From Baseline of ECG Results - QT Interval | Week 24 | -11.2 msec | Standard Deviation 12.99 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QT Interval | Week 4 | -0.5 msec | Standard Deviation 9.47 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QT Interval | Week 52 | -15.3 msec | Standard Deviation 21.73 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QT Interval | Week 24 | 0.6 msec | Standard Deviation 22.1 |
| CC-90001 400mg | Mean Change From Baseline of ECG Results - QT Interval | Week 12 | -2.0 msec | Standard Deviation 27.22 |
| Placebo | Mean Change From Baseline of ECG Results - QT Interval | Week 52 | 8.0 msec | Standard Deviation 25.46 |
| Placebo | Mean Change From Baseline of ECG Results - QT Interval | Week 12 | -3.3 msec | Standard Deviation 17.33 |
| Placebo | Mean Change From Baseline of ECG Results - QT Interval | Week 24 | 13.5 msec | Standard Deviation 27.07 |
| Placebo | Mean Change From Baseline of ECG Results - QT Interval | Week 4 | 1.0 msec | Standard Deviation 13.48 |
Secondary
Number of Participants With Treatment Related Safety Events
Number of participants with treatment related safety events
Time frame: From baseline up to week 52
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CC-90001 100mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE | 10 participants |
| CC-90001 100mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE related to study drug | 4 participants |
| CC-90001 100mg | Number of Participants With Treatment Related Safety Events | Participants with at least one serious TEAE | 2 participants |
| CC-90001 100mg | Number of Participants With Treatment Related Safety Events | Participants with at least one serious TEAE related to study drug | 0 participants |
| CC-90001 100mg | Number of Participants With Treatment Related Safety Events | Participants with at least one grade 3/4 TEAE | 2 participants |
| CC-90001 100mg | Number of Participants With Treatment Related Safety Events | Participants with at least one grade 3/4 TEAE related to study drug | 0 participants |
| CC-90001 100mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE leading to dose interruption | 2 participants |
| CC-90001 100mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE leading to being withdrawn from study drug | 0 participants |
| CC-90001 200mg | Number of Participants With Treatment Related Safety Events | Participants with at least one grade 3/4 TEAE related to study drug | 1 participants |
| CC-90001 200mg | Number of Participants With Treatment Related Safety Events | Participants with at least one grade 3/4 TEAE | 1 participants |
| CC-90001 200mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE related to study drug | 5 participants |
| CC-90001 200mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE leading to being withdrawn from study drug | 1 participants |
| CC-90001 200mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE leading to dose interruption | 1 participants |
| CC-90001 200mg | Number of Participants With Treatment Related Safety Events | Participants with at least one serious TEAE related to study drug | 1 participants |
| CC-90001 200mg | Number of Participants With Treatment Related Safety Events | Participants with at least one serious TEAE | 1 participants |
| CC-90001 200mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE | 13 participants |
| CC-90001 400mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE leading to dose interruption | 2 participants |
| CC-90001 400mg | Number of Participants With Treatment Related Safety Events | Participants with at least one serious TEAE | 2 participants |
| CC-90001 400mg | Number of Participants With Treatment Related Safety Events | Participants with at least one serious TEAE related to study drug | 0 participants |
| CC-90001 400mg | Number of Participants With Treatment Related Safety Events | Participants with at least one grade 3/4 TEAE | 2 participants |
| CC-90001 400mg | Number of Participants With Treatment Related Safety Events | Participants with at least one grade 3/4 TEAE related to study drug | 0 participants |
| CC-90001 400mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE leading to being withdrawn from study drug | 0 participants |
| CC-90001 400mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE | 12 participants |
| CC-90001 400mg | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE related to study drug | 10 participants |
| Placebo | Number of Participants With Treatment Related Safety Events | Participants with at least one serious TEAE | 0 participants |
| Placebo | Number of Participants With Treatment Related Safety Events | Participants with at least one serious TEAE related to study drug | 0 participants |
| Placebo | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE related to study drug | 3 participants |
| Placebo | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE | 10 participants |
| Placebo | Number of Participants With Treatment Related Safety Events | Participants with at least one grade 3/4 TEAE | 1 participants |
| Placebo | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE leading to being withdrawn from study drug | 0 participants |
| Placebo | Number of Participants With Treatment Related Safety Events | Participants with at least one TEAE leading to dose interruption | 0 participants |
| Placebo | Number of Participants With Treatment Related Safety Events | Participants with at least one grade 3/4 TEAE related to study drug | 0 participants |
Secondary
Percentage of Participants Who Progressed to Cirrhosis
Percentage of participants who progressed to cirrhosis
Time frame: From baseline up to week 52
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC-90001 100mg | Percentage of Participants Who Progressed to Cirrhosis | 0 Percentage of Participants |
| CC-90001 200mg | Percentage of Participants Who Progressed to Cirrhosis | 0 Percentage of Participants |
| CC-90001 400mg | Percentage of Participants Who Progressed to Cirrhosis | 7.7 Percentage of Participants |
| Placebo | Percentage of Participants Who Progressed to Cirrhosis | 6.7 Percentage of Participants |
Secondary
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.
Time frame: From baseline up to week 52
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC-90001 100mg | Percentage of Participants With Improvement in Total NAS | 7.7 Percentage of Participants |
| CC-90001 200mg | Percentage of Participants With Improvement in Total NAS | 6.7 Percentage of Participants |
| CC-90001 400mg | Percentage of Participants With Improvement in Total NAS | 15.4 Percentage of Participants |
| Placebo | Percentage of Participants With Improvement in Total NAS | 13.3 Percentage of Participants |
Secondary
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
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC-90001 100mg | Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52 | 15.4 Percentage of Participants |
| CC-90001 200mg | Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52 | 0 Percentage of Participants |
| CC-90001 400mg | Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52 | 7.7 Percentage of Participants |
| Placebo | Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52 | 6.7 Percentage of Participants |
Secondary
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
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC-90001 100mg | Percentage of Participants With Resolution of NASH | 15.4 Percentage of Participants |
| CC-90001 200mg | Percentage of Participants With Resolution of NASH | 0 Percentage of Participants |
| CC-90001 400mg | Percentage of Participants With Resolution of NASH | 7.7 Percentage of Participants |
| Placebo | Percentage of Participants With Resolution of NASH | 6.7 Percentage of Participants |
Secondary
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
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC-90001 100mg | Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis | 15.4 Percentage of Participants |
| CC-90001 200mg | Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis | 0 Percentage of Participants |
| CC-90001 400mg | Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis | 7.7 Percentage of Participants |
| Placebo | Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis | 6.7 Percentage of Participants |
Secondary
Tmax
Tmax is defined is the time to maximum plasma concentration
Time frame: Day 1 and at Week 4
Population: PK evaluable population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CC-90001 100mg | Tmax | Day 1 | 2.0 hours |
| CC-90001 100mg | Tmax | Week 4 | 2.0 hours |
| CC-90001 400mg | Tmax | Day 1 | 2.0 hours |
| CC-90001 400mg | Tmax | Week 4 | 4.0 hours |