Trial Outcomes & Findings for Prevention of De Novo HCV With Antiviral HCV Therapy Post-Liver and Post-Kidney Transplant (NCT NCT03619837)
NCT ID: NCT03619837
Last Updated: 2021-03-03
Results Overview
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.
COMPLETED
PHASE4
122 participants
12 weeks after end of treatment
2021-03-03
Participant Flow
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.
Participant milestones
| Measure |
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.
|
|---|---|
|
Screening
STARTED
|
122
|
|
Screening
COMPLETED
|
24
|
|
Screening
NOT COMPLETED
|
98
|
|
Main Study
STARTED
|
24
|
|
Main Study
COMPLETED
|
24
|
|
Main Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Screening
received organs from HCV-negative donors
|
47
|
|
Screening
died on the wait-list
|
2
|
|
Screening
remained on the wait list
|
40
|
|
Screening
didn't meet eligibility criteria
|
3
|
|
Screening
withdrew consent
|
2
|
|
Screening
never listed for HCV-viremic donor
|
1
|
|
Screening
developed exclusion criteria
|
2
|
|
Screening
excluded by the investigator due to non-compliance
|
1
|
Baseline Characteristics
Prevention of De Novo HCV With Antiviral HCV Therapy Post-Liver and Post-Kidney Transplant
Baseline characteristics by cohort
| Measure |
Transplant Recipients
n=24 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
57 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
20 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Black
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
|
Etiology of end-stage disease
nonalcohol steatohepatitis
|
5 Participants
n=5 Participants
|
|
Etiology of end-stage disease
alcohol
|
4 Participants
n=5 Participants
|
|
Etiology of end-stage disease
HCV/alcohol
|
2 Participants
n=5 Participants
|
|
Etiology of end-stage disease
alpha-1-anti-trypsin deficiency
|
1 Participants
n=5 Participants
|
|
Etiology of end-stage disease
hemochromatosis
|
1 Participants
n=5 Participants
|
|
Etiology of end-stage disease
hypertension
|
4 Participants
n=5 Participants
|
|
Etiology of end-stage disease
diabetes
|
1 Participants
n=5 Participants
|
|
Etiology of end-stage disease
polycystic disease
|
2 Participants
n=5 Participants
|
|
Etiology of end-stage disease
chronic nephritis
|
2 Participants
n=5 Participants
|
|
Etiology of end-stage disease
immunoglobulin A nephropathy
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 weeks after end of treatmentPopulation: 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.
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.
Outcome measures
| Measure |
Treatment Arm
n=23 Participants
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.
|
|---|---|
|
Proportion of Participants With HCV RNA Level Below Limits of Quantification (LOQ)
|
23 Participants
|
SECONDARY outcome
Timeframe: 12 weeks after start of treatmentPopulation: 1 participant did not develop HCV viremia post transplant therefore was not included in the count of participants for this outcome.
1 of 23 patients prematurely discontinued antiviral therapy due to intercurrent graft-versus-host disease that progressed to multiorgan failure.
Outcome measures
| Measure |
Treatment Arm
n=23 Participants
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.
|
|---|---|
|
Safety as Measured by the Proportion of Participants Who Prematurely Discontinue Antiviral Therapy Before the Planned End of Treatment
|
1 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 months from time of liver transplantGraft and patient survival at 24 weeks after transplant
Outcome measures
| Measure |
Treatment Arm
n=24 Participants
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.
|
|---|---|
|
Survival Rate of Patients and Their Allografts 6 Months Post Transplant
|
23 Participants
|
Adverse Events
Transplant Recipients
Serious adverse events
| Measure |
Transplant Recipients
n=24 participants at risk
Treatment Arm Single Arm: Sofosbuvir/Velpatasvir
Dosage: 400mg/100mg. Once daily for 12 weeks.
|
|---|---|
|
Immune system disorders
GVHD
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Immune system disorders
Rejection
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Hepatobiliary disorders
Biliary sclerosis
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Cardiac disorders
cardiomyopathy
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Infections and infestations
Fever
|
20.8%
5/24 • Number of events 7 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Hepatobiliary disorders
Cholangitis
|
8.3%
2/24 • Number of events 2 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
8.3%
2/24 • Number of events 2 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Renal and urinary disorders
Delayed graft function
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Renal and urinary disorders
Ureteral stricture
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Cardiac disorders
Supraventricular tachycardia
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Gastrointestinal disorders
Colitis
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Surgical and medical procedures
Bleeding
|
8.3%
2/24 • Number of events 2 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Surgical and medical procedures
Pancreatitis
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Gastrointestinal disorders
Gastrointestinal bleeding
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Renal and urinary disorders
hyperkalemia
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
Other adverse events
| Measure |
Transplant Recipients
n=24 participants at risk
Treatment Arm Single Arm: Sofosbuvir/Velpatasvir
Dosage: 400mg/100mg. Once daily for 12 weeks.
|
|---|---|
|
Hepatobiliary disorders
abnormal liver tests
|
20.8%
5/24 • Number of events 5 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Blood and lymphatic system disorders
anemia
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Gastrointestinal disorders
nausea
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Renal and urinary disorders
hematuria
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Renal and urinary disorders
Elevated creatinine
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
|
Blood and lymphatic system disorders
leukopenia
|
4.2%
1/24 • Number of events 1 • 6 months
AEs were graded using the Common Terminology Criteria for Adverse Events, Version 4.03, published June 2010
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place