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Heart FailurePhase 1/2USHERNCT03146741

Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors (HCV)

A Phase 1/2 study testing Zepatier in people with Heart Failure, run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is being conducted to determine safety and effectiveness of transplanting hearts from Hepatitis C-positive donors into Hepatitis C-negative patients on the heart transplant waitlist, who will then be treated with Zepatier after transplantation. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Heart Failure
What is being tested?
Zepatier
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
16 May 2017to 30 Nov 2019
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • New York Heart Association (NYHA) Class III or IV CHF refractory to maximal medical therapy (ACE inhibitor, B-blocker, digoxin and diuretics, resynchronization therapy or Implantable Cardioverter Defibrillator when applicable) and/or conventional surgery.
  • Inoperable coronary artery disease with intractable anginal symptoms
  • Malignant ventricular arrhythmias unresponsive to medical or surgical therapy
  • 18-65 years of age
  • Obtained agreement for participation from the transplant cardiology team
  • No evident contraindication to liver transplantation other than the underlying cardiac disorder
Show all 12Show fewer
  • Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 6 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
  • Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA by week 4 post-heart transplantation
  • Able to provide informed consent

Who cannot join

  • Hepatocellular carcinoma
  • HIV positive
  • HCV antibody positive and/or RNA positive
  • Hepatitis B surface antigen, core antibody, and/or DNA positive
  • Any other chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD) with abnormal liver enzymes
  • Persistently elevated liver transaminases
Show all 58Show fewer
  • Congenital heart disease
  • Fibrosis by liver biopsy or total bilirubin > 2.5 with associated evidence of synthetic dysfunction.
  • 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
  • Waitlisted for a multi-organ transplant
  • 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.
  • Chronic bronchitis, chronic obstructive pulmonary disease, inability to stop smoking.
  • Hematologic: Significant coagulation abnormalities, bleeding diatheses.
  • Psychosocial: Profound neurocognitive impairment with absence of social support.
  • Active mental illness or psychosocial instability
  • Inadequate insurance or financial support for post-transplant care.
  • Evidence of drug, tobacco or alcohol abuse within the past six months and completion of recommended therapy/services or meets satisfied parameters as indicated by social work staff and/or consult team.
  • History of chronic non-compliance.
  • Amyloidosis (restricted to cardiac only, without evidence of extra cardiac involvement)
  • BMI ≥38
  • Active peptic ulcer disease.
  • Severe malnutrition.
  • Major chronic disabling illness (e.g. lupus, severe arthritis, neurologic diseases, previous stroke with profound residual).
  • Pulmonary infarction within the past 6 weeks
  • Severe pulmonary hypertension as evidenced by a fixed pulmonary vascular resistance of greater than 4 Wood units on appropriate medical therapy.
  • Patient refusal to receive blood products or transfusions during heart transplant surgery.
  • Severe chronic obstructive pulmonary disease
  • Current clinical sepsis.
  • Symptomatic or severe vascular disease.
  • Chronic Kidney Disease Stage IV, Glomerular Filtration Rate < 30
  • History of Mantle radiation.
  • Asymptomatic renal cell carcinoma <1 year from curative treatment.
  • Symptomatic renal cell carcinoma <5 years from curative treatment.
  • Prostate cancer <2 years from curative treatment.
  • Uterine or cervical cancer <2 years from curative treatment.
  • Any other cancer other than the above including malignant melanoma, < 5 years from treatment apart from other skin malignancies.
  • Donor Organ Selection Criteria:
  • General criteria (although there can be exceptions on a case-by-case basis)
  • Detectable HCV RNA
  • Genotype 1 or 4 HCV
  • Age <=55 years
  • No history of coronary artery disease
  • No congenital heart disease except a repaired atrial septal defect (ASD) provided the patient has normal right ventricular function
  • No history of arrhythmia (atrial fibrilation, atrial flutter or VT) except during resuscitation from fatal event.
  • No evidence of cirrhosis
  • Echocardiographic criteria:
  • Left ventricular ejection fraction (LVEF) >=50%
  • Normal right ventricular function
  • No left ventricular hypertrophy (LVH) - septal wall thickness <1 cm
  • No left ventricular hypertrophy (LVH)- posterior wall thickness <1 cm
  • No significant valvular heart disease - more than mild tricuspid regurgitation, more than mild mitral regurgitation, more than trace aortic regurgitation. No mitral or aortic stenosis.
  • No congenital heart disease - transposition of the great vessels, ventricular septal defect (VSD), ASD, and/or single ventricle (Fontan)
  • Right heart catheterization criteria:
  • Right atrial pressure <=10mmHg
  • Pulmonary capillary wedge pressure <=18mmHg
  • CI >=2.1 l/min/m2
  • Pulmonary hypertension is allowed if the patient has normal right ventricular function and a normal tricuspid valve

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Open-Labeled Trial Of Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors

This study is being conducted to determine safety and effectiveness of transplanting hearts from Hepatitis C-positive donors into Hepatitis C-negative patients on the heart transplant waitlist, who will then be treated with Zepatier after transplantation.

Read the detailed description

Open-labelled pilot clinical trial of Zepatier (MK-5172 and MK-8742/Grazoprevir + Elbasvir) in at least 20 HCV-negative subjects receiving a heart transplant from a HCV-positive donor. Eligible subjects will receive a heart transplant from a deceased-donor with genotype 1 or 4 HCV, and then will receive 12 weeks of Zepatier after heart transplantation when infection with HCV is confirmed in these heart transplant recipients. Treatment will be complete after 12 weeks.

Conditions
Heart Failure
Being tested
Zepatier
Keywords
Heart Failure
Medical subject headings
Heart Failure

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.

Study groups in NCT03146741
Study groupRoleWhat they receive
Zepatier (grazoprevir 100mg and elbasvir 50 mg)ExperimentalNot described
Receives: Drug: Zepatier

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Post-treatment Sustained Virologic Response (SVR)

    The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR; negative HCV RNA after completing Zepatier therapy) / (number of subjects treated with Zepatier post-heart transplantation)

    Measured: Baseline to 24 weeks

  2. Number of Severe Adverse Events (SAE) Attributable to HCV Therapy Post-heart Transplant

    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.

  1. First posted10 May 2017
  2. Study start16 May 2017
  3. Primary completion10 Sep 2019
  4. Study completion30 Nov 2019

Resources

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
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03146741
Sponsor's protocol ID
826708
Acronym
USHER
Status last verified
Nov 2021
First submitted
27 Apr 2017
Last updated
22 Nov 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Sulkowski M, Hezode C, Gerstoft J, Vierling JM, Mallolas J, Pol S, Kugelmas M, Murillo A, Weis N, Nahass R, Shibolet O, Serfaty L, Bourliere M, DeJesus E, Zuckerman E, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015 Mar 21;385(9973):1087-97. doi: 10.1016/S0140-6736(14)61793-1. Epub 2014 Nov 11.

    PubMed 25467560

  • Lawitz E, Gane E, Pearlman B, Tam E, Ghesquiere W, Guyader D, Alric L, Bronowicki JP, Lester L, Sievert W, Ghalib R, Balart L, Sund F, Lagging M, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015 Mar 21;385(9973):1075-86. doi: 10.1016/S0140-6736(14)61795-5. Epub 2014 Nov 11.

    PubMed 25467591

  • Forns X, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Buti M. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.

    PubMed 25895428

  • Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z, Zhao Y, Brown DD, Wan S, DiNubile MJ, Nguyen BY, Robertson MN, Wahl J, Barr E, Butterton JR. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med. 2015 Jul 7;163(1):1-13. doi: 10.7326/M15-0785.

    PubMed 25909356

  • O'Leary JG, Neri MA, Trotter JF, Davis GL, Klintmalm GB. Utilization of hepatitis C antibody-positive livers: genotype dominance is virally determined. Transpl Int. 2012 Aug;25(8):825-9. doi: 10.1111/j.1432-2277.2012.01498.x. Epub 2012 May 30.

    PubMed 22643162

  • Reese PP, Abt PL, Blumberg EA, Goldberg DS. Transplanting Hepatitis C-Positive Kidneys. N Engl J Med. 2015 Jul 23;373(4):303-5. doi: 10.1056/NEJMp1505074. No abstract available.

    PubMed 26200976

  • Reddy KR FS, et al. Ledipasvir/Sofosbuvir with Ribavirin for the Treatment of HCV in Patients with Post Transplant Recurrence: Preliminary Results of a Prospective, Multicenter Study. Hepatology. 2014;60:200A.

  • Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londono MC, Hassanein T, Zamor PJ, Zuckerman E, Wan S, Jackson B, Nguyen BY, Robertson M, Barr E, Wahl J, Greaves W. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015 Oct 17;386(10003):1537-45. doi: 10.1016/S0140-6736(15)00349-9. Epub 2015 Oct 5.

    PubMed 26456905

  • Van Deerlin, V. (December 2015). Hepatitis C Virus Genotyping (GenMark Assay) Validation Summary.

  • Pawlak R RJ, Maranan G, Michel-Treil V, Schutzbank T. A Comparative Evaluation of the Siemens VERSANT HCV Genotype 2.0 (LiPA) and GenMark eSensor HCV Direct Genotyping Tests. CVS 2013 Covance; 2013

  • Dahl A HD, Ogorek T, Hansen G. Comparison of the GenMark Direct Genotype Assay with the LiPA Genotype Assay Using a Diverse Spectrum of HCV Clinical Samples Encountered in a High Risk Inner City HCV Population. CVS 2013 Hennepin; 2013.

  • Woodberry M SK, Castor J, Cook L, Jerome K. Genotyping of Hepatitis C Virus by the Genmark DX Esensor HCVG Direct Test. CVS 2013 UW-Seattle 2013

  • U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. (June 2010). Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

  • Merck Sharp & Dohme Corporation (January 2016). ZEPATIER™ tablets. Highlights of Prescribing Information. 2016.

  • Merck Sharp & Dohme Corporation (July 2015). Elbasvir (MK-8742). Investigator's Brochure (8th Ed.). 2015.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Zepatier in people with Heart Failure, 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 12 inclusion and 58 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 22 Nov 2021. 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 26 Feb 2020). 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?

Number of Participants With Post-treatment Sustained Virologic Response (SVR) (time frame: Baseline to 24 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?

On the ClinicalTrials.gov record for NCT03146741, which also lists 16 linked publications.

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 22 Nov 2021.

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