Hepatitis C, Transplantation Disease Transmission
Conditions
Brief summary
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.
Interventions
Sofosbuvir/Velpatasvir starting early post-transplant for total of 12 weeks.
Only for patients who fail initial treatment with Sofosbuvir/Velpatasvir. Dosage: 400mg/100mg/100mg daily for 12 weeks.
Sponsors
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Adult (≥ 18 year-old), wait-listed for primary kidney or liver transplant without a potential suitable living donor or for simultaneous liver kidney transplant; * HCV non-infected at the time of transplant. Subjects who were previously HCV infected but who have had documented SVR12 are eligible to participate; * Agree to use two methods of birth control during the study; * Donor characteristics: serum HCV NAT-positive and negative for hepatitis B surface antigen. For liver transplant: pre-donation liver biopsy with no fibrosis (F0) or minimal fibrosis (F1). For kidney transplant: kidney donor profile index \< 85%.
Exclusion criteria
* Donor and/or recipient HIV infection * Subject pregnant or nursing * Donor and/or recipient Hepatitis B surface antigen positive * Kidney-pancreas transplant * Single organ liver recipients who received hemodialysis for more than 7 days prior to liver transplantation * Kidney recipients: on dialysis for \> 5 years at time of Screening; subjects sensitized with panel reactive antibody \> 80%; for single organ kidney transplant, subjects with advanced liver fibrosis (Knodell stage 3) or cirrhosis * Individuals being treated with and needing to continue rifabutin, rifampin, carbamazepine, phenytoin, phenobarbital, oxcarbazepine, St. John's wort (Hypericum perforatum), medium- or high-dose rosuvastatin or atorvastatin, or high-dose proton pump inhibitors (See Concomitant Medications). * Individuals treated with amiodarone within 42 days of organ transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With HCV RNA Level Below Limits of Quantification (LOQ) | 12 weeks after end of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety as Measured by the Proportion of Participants Who Prematurely Discontinue Antiviral Therapy Before the Planned End of Treatment | 12 weeks after start of treatment | 1 of 23 patients prematurely discontinued antiviral therapy due to intercurrent graft-versus-host disease that progressed to multiorgan failure. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Survival Rate of Patients and Their Allografts 6 Months Post Transplant | 6 months from time of liver transplant | Graft and patient survival at 24 weeks after transplant |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Screening | developed exclusion criteria | 2 |
| Screening | didn't meet eligibility criteria | 3 |
| Screening | died on the wait-list | 2 |
| Screening | excluded by the investigator due to non-compliance | 1 |
| Screening | never listed for HCV-viremic donor | 1 |
| Screening | received organs from HCV-negative donors | 47 |
| Screening | remained on the wait list | 40 |
| Screening | withdrew consent | 2 |
Baseline characteristics
| Characteristic | Transplant Recipients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 57 years |
| Etiology of end-stage disease alcohol | 4 Participants |
| Etiology of end-stage disease alpha-1-anti-trypsin deficiency | 1 Participants |
| Etiology of end-stage disease chronic nephritis | 2 Participants |
| Etiology of end-stage disease diabetes | 1 Participants |
| Etiology of end-stage disease HCV/alcohol | 2 Participants |
| Etiology of end-stage disease hemochromatosis | 1 Participants |
| Etiology of end-stage disease hypertension | 4 Participants |
| Etiology of end-stage disease immunoglobulin A nephropathy | 2 Participants |
| Etiology of end-stage disease nonalcohol steatohepatitis | 5 Participants |
| Etiology of end-stage disease polycystic disease | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants |
| Race/Ethnicity, Customized Race Black | 3 Participants |
| Race/Ethnicity, Customized Race White | 20 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 24 |
| other Total, other adverse events | 7 / 24 |
| serious Total, serious adverse events | 13 / 24 |
Outcome results
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.
Time frame: 12 weeks after end of treatment
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm | Proportion of Participants With HCV RNA Level Below Limits of Quantification (LOQ) | 23 Participants |
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.
Time frame: 12 weeks after start of treatment
Population: 1 participant did not develop HCV viremia post transplant therefore was not included in the count of participants for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm | Safety as Measured by the Proportion of Participants Who Prematurely Discontinue Antiviral Therapy Before the Planned End of Treatment | 1 Participants |
Other Pre-specified
Survival Rate of Patients and Their Allografts 6 Months Post Transplant
Graft and patient survival at 24 weeks after transplant
Time frame: 6 months from time of liver transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm | Survival Rate of Patients and Their Allografts 6 Months Post Transplant | 23 Participants |