Recurrent Hepatitis C
Conditions
Keywords
Fibrosis progression, recurrent hepatitis C, viral infection, liver transplant recipients, everolimus, Hepatitis C recurrence after orthotopic liver transplantation (OLT)
Brief summary
This study will assess the efficacy of everolimus as an inhibitor of fibrosis progression in liver transplant patients who have a recurrence of hepatitis C viral infection in the transplant
Interventions
DRUGCsA-TAC (standard Treatment)
Continuation of current immunosuppressive regimen (continuation of CNI with or without MPA, with or without steroids) / no everolimus introduction.
DRUGEverolimus
Hepatitis C recurrence after orthotopic liver transplantation (OLT)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients 18 - 65 years of age * Recipients of deceased or living donors * Patients who had undergone primary liver transplantation at least 6 months before enrolment * Recurrent Hepatitis C viral infection and histologically confirmed liver fibrosis (stage I-IV in the Ishak-Knodell scale) obtained at baseline or within the previous 6 months to the date of enrolment * Patients receiving tacrolimus or cyclosporine micro-emulsion with or without - Mycophenolic acid (MPA), with or without steroids. * Absence of acute rejection episodes within the previous 6 months to the date of enrolment * Patient in whom an allograft biopsy will not be contraindicated * Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 24 months * Patients with Hepatocellular carcinoma (HCC) within the University California, San Francisco (UCSF) Criteria and no recurrence for at least 18 months after OLT.
Exclusion criteria
* Recipients of multiple organ transplants or patients who have undergone retransplantation * Current biliary complications * History of drug or alcohol abuse within 1 year before enrolment * Patients treated with anti-hepatitis C virus treatment at the time of enrollment or within the previous month to the date of enrolment * Co-infection with Hepatitis B virus (HBV) or Human Immunodeficiency Virus (HIV) * Patients with Leukocyte count (WBC) \< 3000/mm3, platelet count \< 75000/mm3 or Hemoglobin (Hb) \< 8 g/dl * Patients with proteinuria \>1g/24 hours * Patient with a current severe systemic infection Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant. | baseline, 24 Months | Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite Decrease in score from baseline indicates improvement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups | 24 Months | — |
| Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months | 12 months, 24 months | — |
| Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups | 12 months, 24 months/EOS | GFR Month 9 value if available, otherwise minimal first year post-randomization available value. Imputation rule of missing Month 24 GFR values: GFR Month 18 value if available, otherwise Month 12 GFR is used. Least square means are from an ANCOVA model containing treatment as factor and baseline eGFR as a covariate. |
| Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Baseline, 12 months, 24 months | Metavir Score: F0=No fibrosis; F1=Portal fibrosis without septa; F2=Portal fibrosis with rare septa; F3=Numerous septa without cirrhosis Decrease in score from baseline indicates improvement |
| Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | baseline, 12 and 24 months | The Fibrosure test is the combination of Fibro-test + Acti-test. FibroTest (FT) was for the assessment of fibrosis. Fibro test was calculated using an original combination of five highly concentrated serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin and gammaglutamyltransferase (GGT). FibroTest scores range from 0.00 to 1.00 where 0.0-0.21 is no fibrosis and \>= 0.59 is cirrhosis. Acti-test was calculated using 6 serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT and alanine aminotransferase (ALT). ActiTest (AT) was used for the assessment of necroinflammatory activity. Test score ranges from 0.00 to 1.00, where 0.00-0.17 indicates no necrosis and \>= 0.61 indicates severe necrosis If 12-month Actitest value was the last available assessment, the value is used to impute the final staging score(End of Study) |
| Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis | baseline to month 24 | Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite. |
| Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | baseline, 12 months, 24 months/EOS | End of Study (EOS) endpoint is the last available assessment on or after Month 12. A reduction of at least two logs in HCV RNA viral load was considered as success |
| Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) | baseline, 12 months, 24 months | Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite |
Countries
Argentina
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction. | 21 |
| Everolimus Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids. | 22 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Problems | 7 | 8 |
| Overall Study | Adverse Event | 0 | 5 |
| Overall Study | Graft Lost | 0 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Standard Treatment | Everolimus | Total |
|---|---|---|---|
| Age Continuous | 60.0 years FULL_RANGE 6.79 | 56.5 years FULL_RANGE 8.01 | 57 years |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 11 Participants | 15 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 21 | 20 / 22 |
| serious Total, serious adverse events | 0 / 21 | 11 / 22 |
Outcome results
Primary
Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant.
Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite Decrease in score from baseline indicates improvement
Time frame: baseline, 24 Months
Population: The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication. Small number of biopsies obtained at Month 24 due to study being prematurely terminated.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| CsA-TAC | Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant. | -0.5 Score on Scale | Full Range 1.2 |
| Everolimus | Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant. | 0.0 Score on Scale | Full Range 0.45 |
Secondary
Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization
Metavir Score: F0=No fibrosis; F1=Portal fibrosis without septa; F2=Portal fibrosis with rare septa; F3=Numerous septa without cirrhosis Decrease in score from baseline indicates improvement
Time frame: Baseline, 12 months, 24 months
Population: The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication. Only participants with observations at baseline and specified timepoints were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| CsA-TAC | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Month 12 (n=18, 14) | 1.0 Scores on a Scale | Full Range 1.04 |
| CsA-TAC | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Month 12-Baseline (n=18, 14) | 0.0 Scores on a Scale | Full Range 0.76 |
| CsA-TAC | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Month 24 (n=8, 5) | 1.0 Scores on a Scale | Full Range 1.04 |
| CsA-TAC | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Month 24-Baseline (n=8, 5) | 0.0 Scores on a Scale | — |
| CsA-TAC | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Baseline (n=18, 14) | 1.0 Scores on a Scale | Full Range 0.84 |
| Everolimus | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Month 24-Baseline (n=8, 5) | 0.0 Scores on a Scale | — |
| Everolimus | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Baseline (n=18, 14) | 1.5 Scores on a Scale | Full Range 0.83 |
| Everolimus | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Month 12 (n=18, 14) | 1.0 Scores on a Scale | Full Range 0.8 |
| Everolimus | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Month 24 (n=8, 5) | 1.0 Scores on a Scale | Full Range 0.89 |
| Everolimus | Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization | Month 12-Baseline (n=18, 14) | 0.0 Scores on a Scale | Full Range 0.85 |
Secondary
Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization
End of Study (EOS) endpoint is the last available assessment on or after Month 12. A reduction of at least two logs in HCV RNA viral load was considered as success
Time frame: baseline, 12 months, 24 months/EOS
Population: The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. If 12-month HCV was the last available assessment, this value is used to impute the End of Study value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CsA-TAC | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | 24 months/EoS (n=20, 20) | 6.9 log10 copies/ml | Standard Deviation 0.69 |
| CsA-TAC | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | Month 12 - baseline (n=20,20) | -0.1 log10 copies/ml | Standard Deviation 0.71 |
| CsA-TAC | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | Monh 24 - baseline (n=20,20) | 0.3 log10 copies/ml | Standard Deviation 0.76 |
| CsA-TAC | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | baseline | 6.6 log10 copies/ml | Standard Deviation 0.69 |
| CsA-TAC | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | 12 months (n=20, 20) | 6.5 log10 copies/ml | Standard Deviation 0.84 |
| Everolimus | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | Month 12 - baseline (n=20,20) | 0.2 log10 copies/ml | Standard Deviation 0.72 |
| Everolimus | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | 24 months/EoS (n=20, 20) | 6.7 log10 copies/ml | Standard Deviation 0.87 |
| Everolimus | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | Monh 24 - baseline (n=20,20) | 0.3 log10 copies/ml | Standard Deviation 0.84 |
| Everolimus | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | baseline | 6.4 log10 copies/ml | Standard Deviation 0.94 |
| Everolimus | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization | 12 months (n=20, 20) | 6.6 log10 copies/ml | Standard Deviation 0.85 |
Secondary
Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups
GFR Month 9 value if available, otherwise minimal first year post-randomization available value. Imputation rule of missing Month 24 GFR values: GFR Month 18 value if available, otherwise Month 12 GFR is used. Least square means are from an ANCOVA model containing treatment as factor and baseline eGFR as a covariate.
Time frame: 12 months, 24 months/EOS
Population: The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CsA-TAC | Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups | 12 Months (n=21, 22) | 62.2 mL/min/1.73^2 | Standard Error 2.95 |
| CsA-TAC | Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups | 24 months (n=20, 18) | 65.5 mL/min/1.73^2 | Standard Error 2.51 |
| Everolimus | Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups | 12 Months (n=21, 22) | 65.6 mL/min/1.73^2 | Standard Error 2.88 |
| Everolimus | Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups | 24 months (n=20, 18) | 71.6 mL/min/1.73^2 | Standard Error 2.65 |
Secondary
Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation)
Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite
Time frame: baseline, 12 months, 24 months
Population: The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CsA-TAC | Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) | Baseline (n= 18, 14) | 1.8 Score on a scale | Standard Deviation 1.04 |
| CsA-TAC | Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) | Month 12 (n = 18, 14) | 1.9 Score on a scale | Standard Deviation 1.02 |
| CsA-TAC | Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) | Month 24 (n = 8, 5) | 2.1 Score on a scale | Standard Deviation 0.35 |
| Everolimus | Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) | Baseline (n= 18, 14) | 2.4 Score on a scale | Standard Deviation 0.93 |
| Everolimus | Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) | Month 12 (n = 18, 14) | 1.9 Score on a scale | Standard Deviation 1 |
| Everolimus | Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) | Month 24 (n = 8, 5) | 2.0 Score on a scale | Standard Deviation 0.71 |
Secondary
Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry
The Fibrosure test is the combination of Fibro-test + Acti-test. FibroTest (FT) was for the assessment of fibrosis. Fibro test was calculated using an original combination of five highly concentrated serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin and gammaglutamyltransferase (GGT). FibroTest scores range from 0.00 to 1.00 where 0.0-0.21 is no fibrosis and \>= 0.59 is cirrhosis. Acti-test was calculated using 6 serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT and alanine aminotransferase (ALT). ActiTest (AT) was used for the assessment of necroinflammatory activity. Test score ranges from 0.00 to 1.00, where 0.00-0.17 indicates no necrosis and \>= 0.61 indicates severe necrosis If 12-month Actitest value was the last available assessment, the value is used to impute the final staging score(End of Study)
Time frame: baseline, 12 and 24 months
Population: The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| CsA-TAC | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | Baseline (n=21,21,21,21) | 0.40 units on a scale | Full Range 0.3 |
| CsA-TAC | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | month 24 (n=1,2,1,2) | 0.60 units on a scale | Full Range 0 |
| CsA-TAC | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | month 12 (n=20,17, 20, 17) | 0.60 units on a scale | Full Range 0.28 |
| CsA-TAC | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | end of study [month 24] (n=20,21,20,21) | 0.60 units on a scale | Full Range 0.32 |
| Everolimus | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | end of study [month 24] (n=20,21,20,21) | 0.50 units on a scale | Full Range 0.26 |
| Everolimus | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | month 12 (n=20,17, 20, 17) | 0.50 units on a scale | Full Range 0.23 |
| Everolimus | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | Baseline (n=21,21,21,21) | 0.50 units on a scale | Full Range 0.25 |
| Everolimus | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | month 24 (n=1,2,1,2) | 0.70 units on a scale | Full Range 0.33 |
| Standard Treatment -Summary of Fibrotest by Treatment | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | end of study [month 24] (n=20,21,20,21) | 0.80 units on a scale | Full Range 0.15 |
| Standard Treatment -Summary of Fibrotest by Treatment | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | Baseline (n=21,21,21,21) | 0.80 units on a scale | Full Range 0.18 |
| Standard Treatment -Summary of Fibrotest by Treatment | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | month 12 (n=20,17, 20, 17) | 0.80 units on a scale | Full Range 0.16 |
| Standard Treatment -Summary of Fibrotest by Treatment | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | month 24 (n=1,2,1,2) | 0.90 units on a scale | Full Range 0 |
| Everolimus - Summary of Fibrotest by Treatment | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | end of study [month 24] (n=20,21,20,21) | 0.70 units on a scale | Full Range 0.17 |
| Everolimus - Summary of Fibrotest by Treatment | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | Baseline (n=21,21,21,21) | 0.80 units on a scale | Full Range 0.13 |
| Everolimus - Summary of Fibrotest by Treatment | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | month 24 (n=1,2,1,2) | 1.0 units on a scale | Full Range 0.04 |
| Everolimus - Summary of Fibrotest by Treatment | Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry | month 12 (n=20,17, 20, 17) | 0.80 units on a scale | Full Range 0.15 |
Secondary
Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months
Time frame: 12 months, 24 months
Population: The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CsA-TAC | Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months | 12 months | 0 participants |
| CsA-TAC | Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months | 24 months | 0 participants |
| Everolimus | Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months | 12 months | 0 participants |
| Everolimus | Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months | 24 months | 1 participants |
Secondary
Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis
Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite.
Time frame: baseline to month 24
Population: Difference Ishak-Knodell Score at End-of-Study The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CsA-TAC | Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis | 38.9 percentage of participants |
| Everolimus | Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis | 7.1 percentage of participants |
Secondary
Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups
Time frame: 24 Months
Population: The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CsA-TAC | Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups | Death | 0 Percentage of Participants |
| CsA-TAC | Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups | Graft Loss | 0 Percentage of Participants |
| CsA-TAC | Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups | Acute Rejection (BPAR) | 0 Percentage of Participants |
| Everolimus | Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups | Death | 4.5 Percentage of Participants |
| Everolimus | Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups | Graft Loss | 4.5 Percentage of Participants |
| Everolimus | Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups | Acute Rejection (BPAR) | 0.0 Percentage of Participants |