Ledipasvir/Sofosbuvir Treatment for Hepatitis C in HCT Recipients.
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|ClinicalTrials.gov Identifier: NCT03279133|
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : September 18, 2017
The prevalence of Hepatitis C Virus (HCV) infection was reported to range between 10% and up to 30% prior to institution of routine HCV screening in recipients of HCT (hematopoietic cell transplantation). In an Italian prospective study 6% of HCT candidates were positive for HCV RNA. HCV in recipients of HCT carries both short-term and long-term consequences. In the short-term those with HCV after hematopoietic cell transplantation have been associated with risk for sinusoidal obstruction syndrome especially in patients with some level of hepatic dysfunction going in to the transplant. In addition, the type of conditioning chemotherapy (e.g., busulfan) and radiation may increase risk for sinusoidal obstruction syndrome. The rate of hematopoietic recovery was found to be lower in HCV infected recipients, with delayed neutrophil and platelet engraftment.
In the long-term, HCV may flare up once immunosuppression is being tapered off. The issue of reactivation of viral hepatitis (HBV and HCV) after HCT has been well documented. The risk for HCV reactivation in allogenic HCT in one study was reported at 100% by 12 months after HCT, with risk for death related to HCV of 8%. Also, of concern is rapid progression of liver disease in long-term survivors of HCV+ HCT. In such patients, cumulative incidence of cirrhosis has been reported in up to 11% and 24% at 15 and 20 years after HCT respectively.
Hepatitis C infection is associated with significant morbidity and mortality, due to the short-term and long-term complications associated with it. Treatment of hepatitis C virus with direct-acting antiviral (DAA) agents pre-hematopoietic cell transplantation (HCT) in candidates with hepatitis C may lead to reduction of both short-term and long-term complications from it.
Treatment with DAA's pre-HCT in candidates with hepatitis C would potentially prevent complications of hepatitis C infection; prevent reactivation of hepatitis C post-HCT, prevent delay in hematopoietic recovery (especially neutrophils and platelet), possibly reduce risk for sinsusoidal obstruction syndrome, prevent relapse of malignancy that could be related to hepatitis C (non-Hodgkin lymphoma), reduce non-relapse mortality and long-term complications (cirrhosis).
|Condition or disease||Intervention/treatment||Phase|
|Hematopoietic Stem Cell Transplantation||Drug: Ledipasvir 90mg/Sofosubvir 400mg||Phase 4|
This is an open-label observational/ feasibility study to treat candidates for HCT infected with hepatitis C prior to the transplantation to reduce the complications associated with hepatitis C in the post-transplant setting.
The study will be conducted at Kaiser Permanente Los Angeles Medical Center and City of Hope National Medical Center, Duarte, CA.
There is no data available on the outcomes of treating hepatitis C with DAA's pre-HCT in candidates with hepatitis C infection. The ASBMT task force made recommendation to consider treating hepatitis C infection pre-HCT based on potential benefits it may be associated with. A single case report has documented benefit of treating a donor infected with hepatitis C prior to stem cell collection with DAA and ribavirin
Subject Population will include autologous or allogeneic HCT candidates (for hematologic malignancy) who have hepatitis C infection. Subjects will be considered treatment-experienced if they have received prior interferon-based therapy. Treatment-experienced patients with prior use of DAA(s) are excluded from study participation.
This study will treat HCV patients prior to HCT, with the goal of reducing early post HCT complications in the first 100 days post HCT followed by measuring outcomes at 2 years post HCT.
Subjects will receive LDV 90mg/SOF 400mg FDC for 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is an open-label pilot, safety, feasibility study to treat candidates for HCT infected with hepatitis C prior to the transplantation to reduce the complications associated with hepatitis C in the post-transplant setting.|
|Masking:||None (Open Label)|
|Official Title:||A Pilot/Feasibility Study of Ledipasvir/Sofosbuvir as Treatment for Hepatitis C in Hematopoietic Cell Transplantation (HCT) Recipients.|
|Actual Study Start Date :||September 1, 2017|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||August 2021|
Experimental: LDV/SOF for 12 weeks.
Ledipasvir 90mg/Sofosubvir 400mg fixed-dose combination (FDC) tablet for 12 weeks.
Drug: Ledipasvir 90mg/Sofosubvir 400mg
Ledipasvir 90mg/Sofosubvir 400mg (LDV/SOF) FDC is to be administered once daily with or without food for12 weeks.
Other Name: Harvoni
- Safety and Tolerability of LDV/SOF Treatment in Candidates for HCT with hepatitis C infection [ Time Frame: 2 year ]To assess the safety and tolerability/feasibility of the two agent combination, ledipasvir and sofosbuvir (LDV/SOF), through evaluation of toxicities, including type frequency, severity, attribution, time course and duration.
- Rate of HCV Relapse Post HCT [ Time Frame: 2 Years ]To estimate the rate of hepatitis C relapse post HCT - until 2 year after HCT
- Effect of Virologic Suppression on Post HCT Complications [ Time Frame: 2 Years ]To evaluate the effect of virologic cure on the short term complications after HCT: hematopoietic recovery (neutrophil and platelet count), liver test abnormality, sinusoidal obstruction syndrome, liver disease decompensation in those with advanced fibrosis
- Proportion of Patients with Sustained Virologic Response at Time of Transplant [ Time Frame: 2 Years ]To estimate the proportion of patients who attained SVR by the time of transplantation (day 0 of HCT), and remain HCV negative at day 30, day 100, day 180, year 1 and year 2 post HCT
- Cumulative Incidence of HCV Relapse [ Time Frame: 2 Years ]To estimate the cumulative incidence of hepatitis C relapse
- Progression of Liver Fibrosis After Transplant [ Time Frame: 2 years ]Monitoring for progression of liver fibrosis post-HCT compared to baseline (prior to initiation of DAA treatment)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03279133
|Contact: Beatriz Ornelas, MBA, CCRPfirstname.lastname@example.org|
|United States, California|
|City of Hope||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Sanjeet Dadwal, MD|
|Kaiser Permanente Los Angeles Medical Center||Recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Beatriz Ornelas, MBA, CCRP 323-783-8977 email@example.com|
|Contact: Helen C Abad, MA 323-783-0945 Helen.C.Abad@kp.org|
|Principal Investigator:||Amandeep Sahota, MD||Kaiser Permanente|