Pilot Study Evaluate Efficacy of Grazoprevir + Elbasvir for 12 or 16 Weeks in Liver Transplant Recipients.

Phase 3

Withdrawn

• Conditions: Hepatitis C; Liver Transplantation
• Interventions: Drug: Grazoprevir 100 mg/day; Drug: Elbasvir 50 mg/d; Drug: Elbasvir 50 mg/day; Drug: Ribavirin 1200 mg/day

• Registration Number: NCT02890719
• Lead Sponsor: Fundacion Clinic per a la Recerca Biomédica

Brief Summary

Pilot, single center, open-label study to evaluate the efficacy and tolerability of Grazoprevir and Elbasvir in HCV GT1 and 4 liver transplant recipients.30 liver transplant recipients with hepatitis C recurrence.

Detailed Description

Not available

Study Timeline

• Status Verified: 2016-08
• Study First Submitted: 2016-08-24
• Study First Submitted QC: 2016-08-31
• Study First Posted: 2016-09-07
• Study Start: 2017-05-02
• Primary Completion: 2017-06-01
• Last Update Submitted: 2017-11-02
• Last Update Posted: 2017-11-06
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Age between 18 and 78 year-old.
• Previous liver transplantation(more than 6 month).
• Genotype 1 and 4 infection.
• Hepatitis C recurrence defined by the presence of abnormal liver function test, positive HCV-RNA, histological signs of hepatitis C recurrence.
• Viral load ≥10000UI/mL.
• Immunosuppression with tacrolimus and/or mycophenolate (Prednisone use is allowed at low dose, ≤10 mg/d).
• Treatment naïve or treatment experienced (Peg-RBV or triple therapy).

Exclusion Criteria

• Genotype 2, 3, 5 or 6 infection.

• Decompensated cirrhosis defined by the presence of actual or previous history of clinical decompensation including ascites, hepatic encephalopathy, variceal bleeding or spontaneous bacterial peritonitis, or a Child-Pugh B or C.

• Hepatocellular carcinoma after liver transplantation.

• Total bilirubin > 3 mg/dL.

• Immunosuppression with cyclosporine or an mTOR inhibitor (everolimus or sirolimus).

• Severe extrahepatic diseases: cardiovascular, respiratory, cerebrovascular and poorly controlled diabetes.

• Platelets < 75 x 109 cells/L.

• Neutrophil count < 0.5 x 109 cells/L.

• Hemoglobin < 9 g/dL.

• Albumin < 3g/dL.

• HIV infection.

• Hepatitis B infection.

• Active intake of toxic amounts of alcohol or recreational drugs.

• Females who are pregnant, become to be pregnant or breastfeeding or males whose partners are pregnant, become to be pregnant or breastfeeding.

• Intake of disallowed medications including(but not limited to):

  1. Antibiotics: clarithromycin, erythromycin, telithromycin, nafcillin, rifampin
  2. Antifungals: itraconazole, ketoconazole, voriconazole
  3. Antihypertensives: nifedipine
  4. Anticonvulsants: carbamazepine, phenytoin, phenobarbital
  5. Bosentan
  6. Modafinil
  7. St.Jonh's Wort
  8. Immunosuppressants: cyclosporin, everolimus, sirolimus
  9. Diabetes agents: glibenclamide, glyburide
  10. Lipid lowering agents: gemfibrozil
  11. Eltrombopag
  12. Lapatinib
  13. HIV medications: efavirenz, etravirine, all ritonavir boosted and unboosted HIV protease inhibitors
  14. Statins: simvastatin, fluvastatin, rosuvastatin at doses greater than 10 mg/d, atorvastatin at doses greater than 10 mg/d.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Genotype 1B	Elbasvir 50 mg/d	treatment 12 weeks
Genotype 1A and 4	Elbasvir 50 mg/day	treatment 16 weeks
Genotype 1A and 4	Ribavirin 1200 mg/day	treatment 16 weeks
Genotype 1A and 4	Grazoprevir 100 mg/day	treatment 16 weeks
Genotype 1B	Grazoprevir 100 mg/day	treatment 12 weeks

Primary Outcome Measures

Name	Time	Method
Sustained virological response	12 weeks post-treatment	Sustained virological response 12 w (SVR24) defined as HCV-RNA undetectable at post-treatment week 12.

Secondary Outcome Measures

Name	Time	Method
Sustained virological response	4 weeks and 24 weeks post-treatment	Sustained virological response 12 ( SVR12) defined as HCV-RNA undetectable at post-treatment weeks 4 and , 24 respectively.
To assess the impact of therapy in kidney function.	24 weeks post-treatment	Elevation Transaminases blood analyses in all visits
To evaluate the beneficial effects of antiviral therapy on renal function.	24 weeks post-treatment	creatinine sample analyses blood analyses in all visits
Tolerability of this combination in liver transplant recipients.	Every visit	Serious advers events evaluation