Trial Outcomes & Findings for A Trial of IDN-6556 in Post Orthotopic Liver Transplant for Chronic HCV (NCT NCT02138253)

NCT ID: NCT02138253

Last Updated: 2019-12-11

Results Overview

At least a one stage reduction from baseline in Ishak Fibrosis Stage. Score F0 No fibrosis F1 Fibrous expansion of some portal areas, with or without short fibrous septa F2 Fibrous expansion of most portal areas, with or without short fibrous septa F3 Fibrous expansion of most portal areas, with occasional portal to portal bridging F4 Fibrous expansion of portal areas, with marked bridging (portal to portal as well as portal to central) F5 Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis) F6 Cirrhosis probable or definite Since the primary analysis used multiple imputation methodology, the numerator and denominator varied across 20 imputations.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 64 participants
• Primary outcome timeframe: 24 months
• Results posted on: 2019-12-11

Participant Flow

Subjects were enrolled from 20 of 35 US sites that obtained IRB approval. First subject randomized Sep 2014, last subject last visit was 15 Feb 2018. A total of 114 subjects were screened, 64 subjects randomized with 41 subjects randomized to emricasan and 23 subjects randomized to placebo. Thirteen subjects discontinued the study.

Participant milestones

Measure	IDN-6556 IDN-6556 25 mg BID IDN-6556	Placebo Placebo BID Placebo: Placebo control
Overall Study STARTED	41	23
Overall Study COMPLETED	32	19
Overall Study NOT COMPLETED	9	4

Reasons for withdrawal

Measure	IDN-6556 IDN-6556 25 mg BID IDN-6556	Placebo Placebo BID Placebo: Placebo control
Overall Study Adverse Event	3	3
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	2	0
Overall Study Non compliance	1	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

A Trial of IDN-6556 in Post Orthotopic Liver Transplant for Chronic HCV

Baseline characteristics by cohort

Measure	IDN-6556 n=41 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=23 Participants Placebo BID Placebo: Placebo control	Total n=64 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=5 Participants	17 Participants n=7 Participants	46 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants	6 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	18 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	17 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	20 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	41 participants n=5 Participants	23 participants n=7 Participants	64 participants n=5 Participants
Baseline Ishak Fibrosis Score Baseline Ishak Fibrosis Score F2	9 participants n=5 Participants	6 participants n=7 Participants	15 participants n=5 Participants
Baseline Ishak Fibrosis Score Baseline Ishak Fibrosis Score F3	20 participants n=5 Participants	7 participants n=7 Participants	27 participants n=5 Participants
Baseline Ishak Fibrosis Score Baseline Ishak Fibrosis Score F4	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Baseline Ishak Fibrosis Score Baseline Ishak Fibrosis Score F5	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Baseline Ishak Fibrosis Score Baseline Ishak Fibrosis Score F6	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Population: The Full Analysis Set (FAS) consisted of all randomized subjects who received at least 1 dose of study drug.

At least a one stage reduction from baseline in Ishak Fibrosis Stage. Score F0 No fibrosis F1 Fibrous expansion of some portal areas, with or without short fibrous septa F2 Fibrous expansion of most portal areas, with or without short fibrous septa F3 Fibrous expansion of most portal areas, with occasional portal to portal bridging F4 Fibrous expansion of portal areas, with marked bridging (portal to portal as well as portal to central) F5 Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis) F6 Cirrhosis probable or definite

Since the primary analysis used multiple imputation methodology, the numerator and denominator varied across 20 imputations.

Outcome measures

Measure	IDN-6556 n=41 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=23 Participants Placebo BID Placebo: Placebo control
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score	25 participants	14 participants

SECONDARY outcome

Timeframe: 24 months

Population: Full analysis set

At least a one stage reduction from baseline in Ishak Fibrosis Stage. Score F0 No fibrosis F1 Fibrous expansion of some portal areas, with or without short fibrous septa F2 Fibrous expansion of most portal areas, with or without short fibrous septa F3 Fibrous expansion of most portal areas, with occasional portal to portal bridging F4 Fibrous expansion of portal areas, with marked bridging (portal to portal as well as portal to central) F5 Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis) F6 Cirrhosis probable or definite

Outcome measures

Measure	IDN-6556 n=32 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=19 Participants Placebo BID Placebo: Placebo control
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score (Observed Cases Only)	25 Participants	14 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Full analysis set, the # of subject analyzed included subjects with an observed Ishak Fibrosis Score at 12 months.

At least a one stage reduction from baseline in Ishak Fibrosis Stage. Score F0 No fibrosis F1 Fibrous expansion of some portal areas, with or without short fibrous septa F2 Fibrous expansion of most portal areas, with or without short fibrous septa F3 Fibrous expansion of most portal areas, with occasional portal to portal bridging F4 Fibrous expansion of portal areas, with marked bridging (portal to portal as well as portal to central) F5 Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis) F6 Cirrhosis probable or definite

Outcome measures

Measure	IDN-6556 n=35 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=20 Participants Placebo BID Placebo: Placebo control
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score	27 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline and 24 months

Population: Full analysis set, the # of subject analyzed included subjects with an observed ALT at 24 months.

Liver function laboratory parameter

Outcome measures

Measure	IDN-6556 n=36 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=21 Participants Placebo BID Placebo: Placebo control
Alanine Aminotransferase (ALT) - Change From Baseline	-3.7 U/L Standard Deviation 10	43.7 U/L Standard Deviation 239.5

SECONDARY outcome

Timeframe: Baseline and 24 months

Population: Full analysis set, the # of subject analyzed included subjects with an observed AST at 24 months.

Liver function laboratory parameter

Outcome measures

Measure	IDN-6556 n=35 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=21 Participants Placebo BID Placebo: Placebo control
Aspartate Aminotransferase (AST) Change From Baseline	-4.0 U/L Standard Deviation 8.5	31.4 U/L Standard Deviation 161.8

SECONDARY outcome

Timeframe: Baseline and 24 months

Population: Full analysis set, the # of subject analyzed included subjects with an observed Caspase 3/7 at 24 months.

Mechanistic biomarker of liver function

Outcome measures

Measure	IDN-6556 n=32 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=19 Participants Placebo BID Placebo: Placebo control
Caspase 3/7 Change From Baseline	-296.1 Raw RLU Standard Deviation 830.3	2081.2 Raw RLU Standard Deviation 10116.4

SECONDARY outcome

Timeframe: Baseline and 24 months

Population: Full analysis set, the # of subject analyzed included subjects with an observed cCK18/M30 at 24 months.

Mechanistic biomarker of liver function.

Outcome measures

Measure	IDN-6556 n=31 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=18 Participants Placebo BID Placebo: Placebo control
cCK18/M30 Change From Baseline	-104.7 U/L Standard Deviation 193.2	-66.1 U/L Standard Deviation 176.9

SECONDARY outcome

Timeframe: Baseline and 24 months

Population: Full analysis set, the # of subject analyzed included subjects with an observed flCK18/M65 at 24 months.

Mechanistic biomarker of liver function

Outcome measures

Measure	IDN-6556 n=32 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=18 Participants Placebo BID Placebo: Placebo control
flCK18/M65 Change From Baseline	-70.2 U/L Standard Deviation 189.0	-98.6 U/L Standard Deviation 311.7

SECONDARY outcome

Timeframe: 24 months

Population: Full analysis set

The Ishak modification of Knodell histological activity index was determined by liver biopsy.

Interface hepatitis

• 0 = None
• 1 = Mild (local, few portal areas)
• 2 = Mild/moderate (focal, most portal areas)
• 3 = Moderate (continuous around <50% of tracts or septa)
• 4 = Severe (continuous around >50% of tracts or septa)

Outcome measures

Measure	IDN-6556 n=41 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=23 Participants Placebo BID Placebo: Placebo control
Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis Interface Hepatitis Score of 0	6 Participants	5 Participants
Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis Interface Hepatitis Score of 1	14 Participants	4 Participants
Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis Interface Hepatitis Score of 2	8 Participants	6 Participants
Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis Interface Hepatitis Score of 3	3 Participants	1 Participants
Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis Interface Hepatitis Score of 4	1 Participants	3 Participants
Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis Missing Interface Hepatitis Score	9 Participants	4 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Full analysis set

The Ishak modification of Knodell histological activity index will be determined by liver biopsy. The four items and their categorizations scores include:

• confluent necrosis

• 0 = None
• 1 = Focal confluent necrosis
• 2 = Zone 3 necrosis in some areas
• 3 = Zone 3 necrosis in most areas
• 4 = Zone 3 necrosis + occasional portal-central bridging
• 5 = Zone 3 necrosis + multiple portal-central bridging
• 6 = Panacinar or multiacinar necrosis

Outcome measures

Measure	IDN-6556 n=41 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=23 Participants Placebo BID Placebo: Placebo control
Ishak Modification of Knodell Histological Index - Confluent Necrosis Confluent necrosis score of 0	32 Participants	19 Participants
Ishak Modification of Knodell Histological Index - Confluent Necrosis Missing confluent necrosis score	9 Participants	4 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Full analysis set

The Ishak modification of Knodell histological activity index will be determined by liver biopsy.

• parenchymal injury (focal lytic necrosis, apoptosis and focal inflammation)

• 0 = None
• 1 = One focus or less per 10× objective
• 2 = Two to four foci per 10× objective
• 3 = Five to ten foci per 10× objective
• 4 = More than ten foci per 10× objective

Outcome measures

Measure	IDN-6556 n=41 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=23 Participants Placebo BID Placebo: Placebo control
Ishak Modification of Knodell Histological Index - Parenchymal Injury Parenchymal Injury Score of 0	1 Participants	2 Participants
Ishak Modification of Knodell Histological Index - Parenchymal Injury Parenchymal Injury Score of 1	22 Participants	9 Participants
Ishak Modification of Knodell Histological Index - Parenchymal Injury Parenchymal Injury Score of 2	5 Participants	7 Participants
Ishak Modification of Knodell Histological Index - Parenchymal Injury Parenchymal Injury Score of 3	4 Participants	1 Participants
Ishak Modification of Knodell Histological Index - Parenchymal Injury Missing Parenchymal Injury Score	9 Participants	4 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Full analysis set

Portal inflammation

• 0 = None
• 1 = Mild, some or all portal areas
• 2 = Moderate, some or all portal areas
• 3 = Moderate/marked, all portal areas
• 4 = Marked, all portal areas

Outcome measures

Measure	IDN-6556 n=41 Participants IDN-6556 25 mg BID IDN-6556	Placebo n=23 Participants Placebo BID Placebo: Placebo control
Ishak Modification of Knodell Histological Index - Portal Inflammation Portal Inflammation Score of 1	11 Participants	4 Participants
Ishak Modification of Knodell Histological Index - Portal Inflammation Portal Inflammation Score of 2	19 Participants	8 Participants
Ishak Modification of Knodell Histological Index - Portal Inflammation Portal Inflammation Score of 3	2 Participants	6 Participants
Ishak Modification of Knodell Histological Index - Portal Inflammation Portal Inflammation Score of 4	0 Participants	1 Participants
Ishak Modification of Knodell Histological Index - Portal Inflammation Missing Portal Inflammation Score	9 Participants	4 Participants

Adverse Events

IDN-6556

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 20 other events

Deaths: 1 deaths

Serious adverse events

Measure	IDN-6556 n=41 participants at risk IDN-6556 25 mg BID IDN-6556	Placebo n=23 participants at risk Placebo BID Placebo: Placebo control
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death	0.00% 0/41 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.	4.3% 1/23 • Number of events 1 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.

Other adverse events

Measure	IDN-6556 n=41 participants at risk IDN-6556 25 mg BID IDN-6556	Placebo n=23 participants at risk Placebo BID Placebo: Placebo control
Gastrointestinal disorders Diarrhea	22.0% 9/41 • Number of events 10 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.	21.7% 5/23 • Number of events 6 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.
Vascular disorders Hypertension	14.6% 6/41 • Number of events 7 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.	17.4% 4/23 • Number of events 9 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.
Gastrointestinal disorders Nausea	17.1% 7/41 • Number of events 10 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.	21.7% 5/23 • Number of events 11 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.
Musculoskeletal and connective tissue disorders Arthralgia	14.6% 6/41 • Number of events 10 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.	8.7% 2/23 • Number of events 7 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.
General disorders Fatigue	19.5% 8/41 • Number of events 8 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.	26.1% 6/23 • Number of events 7 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.
Gastrointestinal disorders Abdominal pain	9.8% 4/41 • Number of events 6 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.	8.7% 2/23 • Number of events 2 • Treatment emergent adverse events were collected from the first day of study drug administration until the subject's last study follow-up visit. All treatment emergent adverse events were collected up to the subsequent follow-up visit of the month 24 month visit.

Additional Information

Steven Mento, Ph.D., CEO

Conatus Pharmaceuticals, Inc.

Phone: 858-376-2622

Email: smento@conatuspharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor has the right to publish the results before the PI.
• Publication restrictions are in place

Restriction type: OTHER