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In this study, subjects that do not have Hepatitis C virus (HCV) will be transplanted with livers or kidneys from donors who do have HCV. Medications that are used to treat HCV will be given to the study subjects shortly after transplant to protect them from developing the problems HCV can cause to the liver.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Arm | Experimental | Single Arm: Sofosbuvir/Velpatasvir Dosage: 400mg/100mg. Once daily for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sofosbuvir/Velpatasvir | Drug | Sofosbuvir/Velpatasvir starting early post-transplant for total of 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants With HCV RNA Level Below Limits of Quantification (LOQ) | The primary outcome was sustained virologic response, defined as HCV RNA below the lower limit of quantification 12 weeks after treatment completion (SVR12). Secondary outcomes included the proportion of patients with SVR24 defined as HCV RNA < lower limit of quantification 24 weeks after the end of treatment; with viral relapse defined as HCV RNA <LLOQ at end of treatment with subsequent quantifiable HCV RNA; and with on-treatment virologic breakthrough defined as > 1 log increase in viral RNA after treatment week 1. Safety was measured as the adverse events and serious adverse events attributed by the investigator to HCV infection or antiviral therapy; the proportion of recipients who prematurely discontinued antiviral therapy before the planned end of treatment; and patient and graft survival at 6 months post-transplant. | 12 weeks after end of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Safety as Measured by the Proportion of Participants Who Prematurely Discontinue Antiviral Therapy Before the Planned End of Treatment | 1 of 23 patients prematurely discontinued antiviral therapy due to intercurrent graft-versus-host disease that progressed to multiorgan failure. | 12 weeks after start of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Survival Rate of Patients and Their Allografts 6 Months Post Transplant | Graft and patient survival at 24 weeks after transplant | 6 months from time of liver transplant |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Claus Niemann, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco | San Francisco | California | 94143 | United States | ||
| University of Colorado Denver |
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From July 13, 2018, to December 21, 2019, 122 patients were recruited from 6 U.S. transplant centers and completed the first part of the informed consent and were enrolled in this trial, and 24 (20%) of these received organs from HCV-viremic donors completed the second consent to receive transplant: 13 liver transplants and 11 kidney transplants.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Arm | Single Arm: Sofosbuvir/Velpatasvir Dosage: 400mg/100mg. Once daily for 12 weeks. Sofosbuvir/Velpatasvir: Sofosbuvir/Velpatasvir starting early post-transplant for total of 12 weeks. Sofosbuvir/Velpatasvir/Voxilaprevir: Only for patients who fail initial treatment with Sofosbuvir/Velpatasvir. Dosage: 400mg/100mg/100mg daily for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Screening |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 18, 2018 |
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| Sofosbuvir/Velpatasvir/Voxilaprevir | Drug | Only for patients who fail initial treatment with Sofosbuvir/Velpatasvir. Dosage: 400mg/100mg/100mg daily for 12 weeks. |
|
| Aurora |
| Colorado |
| 80045 |
| United States |
| Piedmont Research Institute | Atlanta | Georgia | 30309 | United States |
| Columbia University | New York | New York | 10032 | United States |
| Baylor University Medical Center - Dallas | Dallas | Texas | 75246 | United States |
| Houston Methodist Hospital | Houston | Texas | 77030 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| Main Study |
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Subjects that do not have Hepatitis C virus (HCV) will be transplanted with livers or kidneys from donors who do have HCV.
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| ID | Title | Description |
|---|---|---|
| BG000 | Transplant Recipients | Single Arm: Sofosbuvir/Velpatasvir Dosage: 400mg/100mg. Once daily for12 weeks. Sofosbuvir/Velpatasvir:Sofosbuvir/Velpatasvir starting early post-transplant for total of 12 weeks. Sofosbuvir/Velpatasvir/Voxilaprevir:Only for patients who fail initial treatment with Sofosbuvir/Velpatasvir. [no patients failed initial treatment] Dosage: 400mg/100mg/100mg daily for12 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||||
| Etiology of end-stage disease | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Participants With HCV RNA Level Below Limits of Quantification (LOQ) | The primary outcome was sustained virologic response, defined as HCV RNA below the lower limit of quantification 12 weeks after treatment completion (SVR12). Secondary outcomes included the proportion of patients with SVR24 defined as HCV RNA < lower limit of quantification 24 weeks after the end of treatment; with viral relapse defined as HCV RNA <LLOQ at end of treatment with subsequent quantifiable HCV RNA; and with on-treatment virologic breakthrough defined as > 1 log increase in viral RNA after treatment week 1. Safety was measured as the adverse events and serious adverse events attributed by the investigator to HCV infection or antiviral therapy; the proportion of recipients who prematurely discontinued antiviral therapy before the planned end of treatment; and patient and graft survival at 6 months post-transplant. | All patients with HC viremia documented post-transplant. 1 participant did not develop HCV viremia post transplant therefore was not included in the count of participants for this outcome. | Posted | Count of Participants | Participants | 12 weeks after end of treatment |
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|
| ||||||||||||||||||||||||||
| Secondary | Safety as Measured by the Proportion of Participants Who Prematurely Discontinue Antiviral Therapy Before the Planned End of Treatment | 1 of 23 patients prematurely discontinued antiviral therapy due to intercurrent graft-versus-host disease that progressed to multiorgan failure. | 1 participant did not develop HCV viremia post transplant therefore was not included in the count of participants for this outcome. | Posted | Count of Participants | Participants | 12 weeks after start of treatment |
|
| |||||||||||||||||||||||||||
| Other Pre-specified | Survival Rate of Patients and Their Allografts 6 Months Post Transplant | Graft and patient survival at 24 weeks after transplant | Posted | Count of Participants | Participants | 6 months from time of liver transplant |
|
|
6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Transplant Recipients | Treatment Arm Single Arm: Sofosbuvir/Velpatasvir Dosage: 400mg/100mg. Once daily for 12 weeks. | 1 | 24 | 13 | 24 | 7 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| GVHD | Immune system disorders | Common Terminology | Systematic Assessment | Subject was diagnosed with GVHD beginning day 19 following transplant. Study drug was started 8 days post_LT but was permanently discontinued after only 7 weeks of treatment per investigator discretion due to multisystem organ complications. |
|
| Rejection | Immune system disorders | Common Terminology | Systematic Assessment | Subject received an A2→O graft and began the study drug 5 days post-transplant developed early antibody-mediated rejection that was treated with intravenous immunoglobulin G with normalization of liver biochemistries by day 36 after transplant. |
|
| Biliary sclerosis | Hepatobiliary disorders | Common Terminology | Systematic Assessment | Subject who began the study drug 6 days after surgery developed a progressive, intrahepatic biliary sclerosis starting by day 31. An ischemic etiology was excluded. No other clinical sequelae other than elevated ALKP. |
|
| cardiomyopathy | Cardiac disorders | Common Terminology | Systematic Assessment | Subject started study treatment 6 days after surgery and found to have idiopathic pericardial effusion with decreased left-ventricular ejection fraction about 1 month after transplant that resolved with pericardiocentesis. |
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| Fever | Infections and infestations | Common Terminology | Systematic Assessment | N=5 without origin; n=1 with diarrhea and n=1 with UTI |
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| Cholangitis | Hepatobiliary disorders | Common Terminology | Systematic Assessment |
| |
| Fracture | Musculoskeletal and connective tissue disorders | Common Terminology | Systematic Assessment | N=1 hip; N=1 humerus |
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| Delayed graft function | Renal and urinary disorders | Common Terminology | Systematic Assessment | Required hemodialysis but recovered. |
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| Ureteral stricture | Renal and urinary disorders | Common Terminology | Systematic Assessment | Associated with acute kidney injury, treated with nephrostomy with resolution |
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| Supraventricular tachycardia | Cardiac disorders | Common Terminology | Systematic Assessment | Intraoperative with liver transplantation; treated with amiodarone |
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| Colitis | Gastrointestinal disorders | Common Terminology | Systematic Assessment | Secondary to C. difficle |
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| Bleeding | Surgical and medical procedures | Common Terminology | Systematic Assessment | Intraabdominal bleeding (post-op - N=2 liver transplant recipients) |
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| Pancreatitis | Surgical and medical procedures | Common Terminology | Systematic Assessment | Post procedural |
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| Gastrointestinal bleeding | Gastrointestinal disorders | Common Terminology | Systematic Assessment |
| |
| hyperkalemia | Renal and urinary disorders | Common Terminology | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| abnormal liver tests | Hepatobiliary disorders | Common Terminology | Systematic Assessment |
| |
| anemia | Blood and lymphatic system disorders | Common Terminology | Systematic Assessment |
| |
| nausea | Gastrointestinal disorders | Common Terminology | Systematic Assessment | with vomiting |
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| hematuria | Renal and urinary disorders | Common Terminology | Systematic Assessment | post kidney biopsy |
|
| Elevated creatinine | Renal and urinary disorders | Common Terminology | Systematic Assessment |
| |
| leukopenia | Blood and lymphatic system disorders | Common Terminology | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Norah Terrault | University of Southern California | 323-442-5100 | terrault@usc.edu |
| Dec 20, 2020 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 19, 2018 | Dec 22, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C000611331 | sofosbuvir-velpatasvir drug combination |
| C000654129 | sofosbuvir velpatasvir voxilaprevir drug combination |
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| Asian |
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| HCV/alcohol |
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| alpha-1-anti-trypsin deficiency |
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| hemochromatosis |
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| hypertension |
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| diabetes |
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| polycystic disease |
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| chronic nephritis |
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| immunoglobulin A nephropathy |
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