A Trial of IDN-6556 in Post Orthotopic Liver Transplant for Chronic HCV (POLT-HCV-SVR)
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| ClinicalTrials.gov Identifier: NCT02138253 |
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Recruitment Status :
Completed
First Posted : May 14, 2014
Results First Posted : December 11, 2019
Last Update Posted : December 11, 2019
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Sponsor:
Conatus Pharmaceuticals Inc.
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.
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Brief Summary:
This is a double-blind, multicenter study involving patients with chronic HCV infection who had a liver transplantation; developed HCV-related liver fibrosis and/or incomplete cirrhosis; achieved a sustained virologic response (SVR) following anti-HCV therapy; but still have fibrosis and/or incomplete cirrhosis on liver biopsy to see if treatment with IDN-6556 is better than placebo in reversing or stopping the progression of the damage to the new liver caused by HCV.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Liver Fibrosis Hepatic Fibrosis Liver Cirrhosis Hepatic Cirrhosis | Drug: IDN-6556 Drug: Placebo | Phase 2 |
There are data to suggest that with eradication of the HCV virus, improvements in liver fibrosis can be seen in the post-transplant population. However, amelioration of inflammatory activity, and deceleration of fibrosis progression is a gradual process over the course of many years. This placebo-controlled study is designed to evaluate the effects of IDN-6556, compared to placebo, on markers of apoptosis and inflammation, and liver histology.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 64 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Double-Blind, Randomized Trial of IDN-6556 in Subjects Who Had Hepatitis C Virus (HCV) Reinfection and Liver Fibrosis Following Orthotopic Liver Transplantation for Chronic HCV Infection and Who Subsequently Achieved a Sustained Virologic Response Following Anti-HCV Therapy |
| Study Start Date : | May 2014 |
| Actual Primary Completion Date : | February 15, 2018 |
| Actual Study Completion Date : | March 9, 2018 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
North American Indian childhood cirrhosis
MedlinePlus related topics:
Liver Transplantation
| Arm | Intervention/treatment |
|---|---|
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Experimental: IDN-6556
IDN-6556 25 mg BID
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Drug: IDN-6556
Other Names:
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Placebo Comparator: Placebo
Placebo BID
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Drug: Placebo
Placebo control |
Primary Outcome Measures :
- Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score [ Time Frame: 24 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
Since the primary analysis used multiple imputation methodology, the numerator and denominator varied across 20 imputations.
Secondary Outcome Measures :
- Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score (Observed Cases Only) [ Time Frame: 24 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
- Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score [ Time Frame: 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
- Alanine Aminotransferase (ALT) - Change From Baseline [ Time Frame: Baseline and 24 months ]Liver function laboratory parameter
- Aspartate Aminotransferase (AST) Change From Baseline [ Time Frame: Baseline and 24 months ]Liver function laboratory parameter
- Caspase 3/7 Change From Baseline [ Time Frame: Baseline and 24 months ]Mechanistic biomarker of liver function
- cCK18/M30 Change From Baseline [ Time Frame: Baseline and 24 months ]Mechanistic biomarker of liver function.
- flCK18/M65 Change From Baseline [ Time Frame: Baseline and 24 months ]Mechanistic biomarker of liver function
- Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis [ Time Frame: 24 months ]
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)
- Ishak Modification of Knodell Histological Index - Confluent Necrosis [ Time Frame: 24 months ]
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
- Ishak Modification of Knodell Histological Index - Parenchymal Injury [ Time Frame: 24 months ]
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
- Ishak Modification of Knodell Histological Index - Portal Inflammation [ Time Frame: 24 months ]
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
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Male or female subjects of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and able to understand and willing to comply with the requirements of the study
- History of orthotopic liver transplantation for HCV-induced liver disease
- Diagnosis of HCV infection (HCV-RNA detectable in serum) and liver fibrosis and/or incomplete cirrhosis status post liver transplantation, and achieved a sustained virologic response (SVR) with anti-viral HCV treatment within 18 months of Day 1
- Liver fibrosis on liver histology as read by central histopathologist of Ishak F2 to F6 within three months of Day 1 (Up to 15 subjects with an Ishak score of F6 can be enrolled)
- Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from Screening to one month after the last dose of study drug
Exclusion Criteria:
- Known infection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV)
- History of renal transplant and/or severe renal impairment defined as eGFR (estimated glomerular filtration rate) of less than 30 mL/min/1.73 m2
- Evidence of tumor burden >Milan criteria, or evidence of micro- or macrovascular invasion in explanted liver
- Hepatocellular carcinoma (HCC) at entry into the study
- Concurrent sirolimus (rapamycin) use
- History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of > 480 milliseconds (msec)
- Subjects with diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA)
- If female: known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
Information from the National Library of Medicine
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): NCT02138253
Locations
Show 35 study locations
Sponsors and Collaborators
Conatus Pharmaceuticals Inc.
Investigators
| Study Chair: | David Hagerty, MD | Conatus Pharmaceuticals |
Study Documents (Full-Text)
Documents provided by Conatus Pharmaceuticals Inc.:
Documents provided by Conatus Pharmaceuticals Inc.:
Study Protocol [PDF] August 3, 2015
Statistical Analysis Plan [PDF] January 18, 2018
| Responsible Party: | Conatus Pharmaceuticals Inc. |
| ClinicalTrials.gov Identifier: | NCT02138253 |
| Other Study ID Numbers: |
IDN-6556-07 |
| First Posted: | May 14, 2014 Key Record Dates |
| Results First Posted: | December 11, 2019 |
| Last Update Posted: | December 11, 2019 |
| Last Verified: | November 2019 |
Keywords provided by Conatus Pharmaceuticals Inc.:
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liver transplant hepatitis C liver fibrosis |
hepatic fibrosis liver cirrhosis hepatic cirrhosis |
Additional relevant MeSH terms:
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Liver Cirrhosis Fibrosis Pathologic Processes Liver Diseases Digestive System Diseases |