Transplanting Hepatitis C Lungs Into Negative Lung Recipients

NCT03724149 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 829397
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to determine safety and effectiveness of transplanting lungs from Hepatitis C-positive donors into Hepatitis C-negative patients on the lung transplant waitlist, who will then be treated with appropriate direct-acting antiviral (DAA) after transplantation.

Conditions

Lung Diseases

Keywords

Lung Disease

Outcome Measures

Primary Outcomes (2)

• Subject Sustained Virologic Response (SVR-12) at 12-weeks Post-treatment

  The primary outcome measure is Sustained Virologic Response (SVR) rate at 12 weeks (number of subjects with SVR; negative HCV RNA after completing therapy) / (number of subjects treated post-lung transplantation). SVR will be based on the standard definition of SVR-12, defined as an undetectable HCV RNA in a subject's serum 12 weeks after completing treatment for HCV (12 weeks after the subject takes the last dose of Zepatier, Epclusa, or another appropriate antiviral treatment).

  Baseline to 12 weeks

• Major Adverse Events Attributable to HCV Therapy in Post-lung Transplant Patients Post-lung Transplant Patients

  Baseline to 52 weeks

Study Arms (1)

Direct-acting antiviral treatment for HCV

EXPERIMENTAL

Drug: Zepatier; Drug: Epclusa

Interventions

Zepatier DRUG

Zepatier (grazoprevir 100mg and elbasvir 50 mg once daily) is taken by mouth for 12 weeks unless a genetic variation is detected. In this case treatment with Zepatier will be extended to 16 weeks. Study subjects with treatment failure will be provided open-label Zepatier + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.

Direct-acting antiviral treatment for HCV

Epclusa DRUG

Epclusa (sofosbuvir 400mg and velpatasvir 100mg once daily) is taken by mouth for 12 weeks. Study subjects with treatment failure will be provided an alternative DAA + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.

Direct-acting antiviral treatment for HCV

Eligibility Criteria

• Age: 18 Years - 67 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• Obtained agreement for participation from the lung transplant team
• No evident contraindication to lung transplantation other than the underlying lung disorder
• Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 12 months after transplantation
• No active illicit substance abuse
• Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant due to the increased risk of birth defects and/or miscarriage
• Both men and women must agree to use at least one barrier method of birth control or remain abstinent following transplant due to risk of HCV transmission
• Able to provide informed consent

You may not qualify if:

• Hepatocellular carcinoma
• HIV positive
• HCV RNA positive
• Hepatitis B surface antigen and/or DNA positive
• Any chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD)) that is occurring in the setting of persistently elevated liver enzymes (patients with Alpha-1-antitrypsin lung disease without hepatic involvement are eligible)
• Significant fibrosis (≥F2 on the Fibroscan)-for patients with cystic fibrosis, the cutoff will be 11kPa (cutoff for F2 for patients with chronic cholestatic liver disease), whereas for all other patients the cutoff will be 8kPa (the cutoff for fatty liver disease used in the THINKER study).
• Pregnant or nursing (lactating) women
• Known allergy or intolerance to tacrolimus that would require post-transplant administration of cyclosporine, rather than tacrolimus given the drug-drug interaction between cyclosporine and Zepatier/Epclusa
• Pre-transplant treatment with amiodarone given the drug-drug interaction between amiodarone and Epclusa
• Waitlisted for a multi-organ transplant
• Patients with underlying liver disease with or without liver cirrhosis
• Patients with cystic fibrosis who have underlying liver disease
• Re-transplant candidate
• Use of ECMO or mechanical ventilation as a bridge to lung transplantation
• Inability to provide study consent

Sponsors & Collaborators

• University of Pennsylvania: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Lung Diseases

Interventions

elbasvir-grazoprevir drug combination; sofosbuvir-velpatasvir drug combination

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Peter Reese
• Organization: Perelman School of Medicine

amussell@upenn.edu

215-900-3782

Study Officials

• Peter Reese, MD, MSCE

  Perelman School of Medicine at the University of Pennsylvania

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2018
• First Posted: October 30, 2018
• Study Start: December 12, 2018
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2022
• Last Updated: April 14, 2023
• Results First Posted: April 14, 2023

Record last verified: 2023-04

Locations

US (1)