Lung DiseasesPhase 1/2SHELTERNCT03724149
Transplanting Hepatitis C Lungs Into Negative Lung Recipients
A Phase 1/2 study testing Zepatier and Epclusa in people with Lung Diseases, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 67 years
- Conditions the study is for
- Lung Diseases
- What is being tested?
- Zepatier and Epclusa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Dec 2018to 31 Dec 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 67 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-67 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
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- 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
- Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA by week 4 post-lung transplantation
- Able to provide informed consent
- Detectable HCV RNA
- Age ≤55 years
- PaO2/FiO2 ≥300 on FiO2 = 100% and PEEP=5
- Cigarette use history ≤20 pack years
- No evidence of cirrhosis
- No prior treatment of HCV with a DAA-based therapy
- Can be isolated hepatitis B Core IgG positive, but cannot have a detectable HBV Core IgM, HBSAg, and/or HBV DNA (positive HBV NAT test)
- Donor Exclusion Criteria:
- Donation after circulatory death determination (DCDD)
- HIV positive
Who cannot join
- 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).
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- 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
- Chronic kidney disease with GFR<50 ml/min/1.73 m^2
- Relative contraindications for study subjects that will be reviewed on a case-by-case basis by the Lung Transplant Selection Committee and the Principal Investigators:
- Evidence of end organ damage due to diabetes (e.g. retinopathy, nephropathy, ulcerations) and /or brittle diabetes mellitus (e.g. history of diabetic ketoacidosis) and/or uncontrolled diabetes as evidence by a HgbA1C of 7.5-8.5.
- Hematologic: Significant coagulation abnormalities, and/or bleeding diatheses.
- Active or recent solid or liquid malignancy in the past 5 years (apart from select skin malignancies).
- Patient refusal to receive blood products or transfusions during lung transplant surgery.
- Psychosocial: Profound neurocognitive impairment with absence of social support.
- Active mental illness or psychosocial instability
- Inadequate insurance and/or financial support for post-transplant care.
- Evidence of drug, tobacco or alcohol abuse within the past six months and failure to satisfy recommended therapy/services/parameters as indicated by social work staff and/or consult team.
- History of chronic non-adherence to medical recommendations and/or medications
- PRA >10%.
- Severe malnutrition, BMI <18
- Major chronic disabling comorbidity (e.g. lupus, severe arthritis, neurologic diseases, previous stroke with profound residual).
- Symptomatic or severe vascular disease (History of CABG, Aorta-femoral surgery)
- Donor Organ Selection Criteria
- Broad goal: To include donors with confirmed HCV expected to have acceptable post-transplant graft outcomes based on large retrospective lung transplant studies.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Open-Labeled Trial Of Direct-acting Antiviral Treatment Of Hepatitis C-Negative Patients Who Receive Lung Transplants From Hepatitis C-Positive Donors
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.
Read the detailed description
Open-labelled pilot clinical trial of Zepatier (Grazoprevir + Elbasvir), Epclusa (Sofosbuvir + Velpatasvir), or another appropriate DAA in at least 10 HCV-negative subjects receiving a lung transplant from a hepatitis C (HCV)-positive donor. Eligible subjects will receive a lung transplant from a deceased-donor, and then will receive treatment after lung transplantation when infection with HCV is confirmed in these lung transplant recipients. Treatment will be complete after 12 weeks for most subjects.
- Conditions
- Lung Diseases
- Being tested
- Zepatier, Epclusa
- Keywords
- Lung Disease
- Medical subject headings
- Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZepatierDrug
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.
EpclusaDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Direct-acting antiviral treatment for HCV | Experimental | Not described Receives: Drug: Zepatier; Drug: Epclusa |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline to 12 weeks
Major Adverse Events Attributable to HCV Therapy in Post-lung Transplant Patients Post-lung Transplant Patients
Measured: Baseline to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2018
- Study start12 Dec 2018
- Primary completion31 Dec 2021
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lung DiseasesStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Peter Reese, MD, MSCE, Study director, Perelman School of Medicine at the University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03724149
- Sponsor's protocol ID
- 829397
- Acronym
- SHELTER
- Status last verified
- Apr 2023
- First submitted
- 26 Oct 2018
- Last updated
- 14 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Labeled Trial Of Direct-acting Antiviral Treatment Of Hepatitis C-Negative Patients Who Receive Lung Transplants From Hepatitis C-Positive Donors
- ClinicalTrials.gov ID
- NCT03724149
- Acronym / sponsor ID
- SHELTER / 829397
- Conditions
- Lung Diseases
- Keywords
- Lung Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 12 Dec 2018 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 30 Oct 2018 (actual)
- Results
- Posted 14 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Open-labelled pilot clinical trial of Zepatier (Grazoprevir + Elbasvir), Epclusa (Sofosbuvir + Velpatasvir), or another appropriate DAA in at least 10 HCV-negative subjects receiving a lung transplant from a hepatitis C (HCV)-positive donor. Eligible subjects will receive a lung transplant from a deceased-donor, and then will receive treatment after lung transplantation when infection with HCV is confirmed in these lung transplant recipients. Treatment will be complete after 12 weeks for most subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Direct-acting antiviral treatment for HCV | Experimental | Drug: Zepatier, Drug: Epclusa |
Who may qualify
- Ages
- 18 to 67 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 18-67 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
Key exclusion criteria (32 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZepatierZepatier (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. | Drug | Direct-acting antiviral treatment for HCV |
| EpclusaEpclusa (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. | Drug | Direct-acting antiviral treatment for HCV |
Primary outcome
Subject Sustained Virologic Response (SVR-12) at 12-weeks Post-treatment
Time frame: Baseline to 12 weeks
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).
Major Adverse Events Attributable to HCV Therapy in Post-lung Transplant Patients Post-lung Transplant Patients
Time frame: Baseline to 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Reese, MD, MSCE study director
Perelman School of Medicine at the University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Zepatier and Epclusa in people with Lung Diseases, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subject Sustained Virologic Response (SVR-12) at 12-weeks Post-treatment (time frame: Baseline to 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2023.