Hematopoietic Stem Cell TransplantationPhase 4NCT03279133
Ledipasvir/Sofosbuvir Treatment for Hepatitis C in HCT Recipients.
A Phase 4 study testing Ledipasvir 90mg/Sofosubvir 400mg in people with Hematopoietic Stem Cell Transplantation, run by Kaiser Permanente at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematopoietic Stem Cell Transplantation
- What is being tested?
- Ledipasvir 90mg/Sofosubvir 400mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Sep 2017to 29 Apr 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be male or female at least 18 years of age at time of screening
- Participant must be able to provide written Informed Consent
- Participant must be able to adhere to study visit/procedure schedule and protocol requirements
- Time available (at least 12 weeks) for treatment of hepatitis C prior to autologous or allogeneic transplantation
- First autologous or allogeneic HCT and hematologic disease in remission on initiation of antiviral therapy for hepatitis C infection
- Patients with myelodysplastic syndrome, aplastic anemia or hemoglobinopathies will be eligible to participate regardless of disease status if plan is to proceed to HCT
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- Female participant without childbearing potential must meet at least one of the following:
- Postmenopausal defined as women >54 years of age with amenorrhea for ≥ 2 years prior to screening
- Surgically sterile defined as bilateral tubal ligation or bilateral oophorectomy or hysterectomy
- Has male sexual partner with vasectomy
- Female participant of childbearing potential must meet at least one of the following:
- Must be using at least 1 effective contraceptive method at screening and agree to practice 2 effective contraceptive methods1 for study duration, starting Screening through 30 days after stopping study drug
- Practice total abstinence from sexual intercourse (minimum 1 complete menstrual cycle)
- Sexually active with female partner only
- Male participant who is not surgically sterile and is sexually active with female partner of childbearing potential must agree to practice 2 effective contraceptive methods1 for study duration, starting at Screening through 30 days after stopping study drug
- Participant must have the following indicator- of chronic hepatitis C virus infection prior to study enrollment:
- Positive for HCV RNA at the time of screening
- Participant screening laboratory result must indicate HCV genotype 1, 4, 5 or 6-infection if historical result is not available.
Who cannot join
- Participant unwilling to provide written informed consent
- Participant unwilling to adhere to study visit/procedure schedule and protocol requirements
- Participant is pregnant or is a breastfeeding female
- Positive test result for hepatitis B surface antigen (HBsAG), hepatitis B core antibody (HBcAb), or confirmed positive anti-HIV antibody test
- Received study contraindicated medications prior to study drug administration including but not limited to those listed in the Full Prescribing Information Sheet for ledipasvir/sofosbuvir (Harvoni®).
- Clinically significant abnormalities or co-morbidities, other than HCV infection that in opinion of the investigator makes subject unsuitable for this study or drug regimen
Show all 17Show fewer
- Prior or current use of any investigational or commercially available anti-HCV agents other than interferon or ribavirin or receipt of any investigational product within 6 weeks prior to study drug administration
- Prior treatment of chronic HCV infection with a direct acting antiviral agent(s): telaprevir, boceprevir, sofosbuvir, simeprevir, or other direct acting antiviral
- History of solid organ transplant
- Screening laboratory analyses shows any of the following abnormal laboratory results:
- Estimated Glomerular filtration (eGFR) rate < 30 mL/min
- Evidence of cirrhosis, documented by one of the following:
- Liver biopsy histologic diagnosis: Metavir Score greater than 3 (includes 3 - 4 or ¾) or Ishak score greater than 4 In the absence of liver biopsy: a FibroScan score greater than or equal to 12.5 kPa or Fibrotest score of >0.75 AND an APRI score greater than 1.5
- History of liver decompensation: ascites noted on a physical exam, imaging or other test; variceal bleeding; hepatic encephalopathy
- Confirmed presence of hepatocellular carcinoma indicated on computed tomography, magnetic resonance, or other imaging techniques within 3 months prior to screening
- HCV genotype performed during screening indicates infection with genotype 2 or 3
- Recent history of drug or alcohol abuse that could, in the opinion of the investigator, affect adherence to the study protocol
Trial locations and contacts
2 sites in 1 country.
United States2 sites
City of Hope
Duarte, California, 91010
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
About this study
Official title: A Pilot/Feasibility Study of Ledipasvir/Sofosbuvir as Treatment for Hepatitis C in Hematopoietic Cell Transplantation (HCT) Recipients.
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.
Read more
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).
Read the detailed description
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.
- Conditions
- Hematopoietic Stem Cell Transplantation
- Being tested
- Ledipasvir 90mg/Sofosubvir 400mg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ledipasvir 90mg/Sofosubvir 400mgDrug
Also called Harvoni
Ledipasvir 90mg/Sofosubvir 400mg (LDV/SOF) FDC is to be administered once daily with or without food for12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| LDV/SOF for 12 weeks. | Experimental | Ledipasvir 90mg/Sofosubvir 400mg fixed-dose combination (FDC) tablet for 12 weeks. Receives: Drug: Ledipasvir 90mg/Sofosubvir 400mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of LDV/SOF Treatment in Candidates for HCT with hepatitis C infection
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.
Measured: 2 year
Secondary outcomes (5)
Rate of HCV Relapse Post HCT
To estimate the rate of hepatitis C relapse post HCT - until 2 year after HCT
Measured: 2 Years
Effect of Virologic Suppression on Post HCT Complications
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
Measured: 2 Years
Proportion of Patients with Sustained Virologic Response at Time of Transplant
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
Measured: 2 Years
Cumulative Incidence of HCV Relapse
To estimate the cumulative incidence of hepatitis C relapse
Measured: 2 Years
Progression of Liver Fibrosis After Transplant
Monitoring for progression of liver fibrosis post-HCT compared to baseline (prior to initiation of DAA treatment)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2017
- Study start1 Sep 2017
- Primary completion16 Feb 2018
- Study completion29 Apr 2018
Why it stopped: Unable to find eligible patients with untreated hepatitis C virus.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematopoietic Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by Kaiser PermanenteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kaiser Permanente
- Sponsor type
- University, hospital or other
- Collaborators
- City of Hope National Medical Center
- Responsible party
- Sponsor
- Investigators
- Amandeep Sahota, MD, Principal investigator, Kaiser Permanente
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03279133
- Sponsor's protocol ID
- IN-US-337-2116
- Status last verified
- Aug 2018
- First submitted
- 8 Sep 2017
- Last updated
- 31 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot/Feasibility Study of Ledipasvir/Sofosbuvir as Treatment for Hepatitis C in Hematopoietic Cell Transplantation (HCT) Recipients.
- ClinicalTrials.gov ID
- NCT03279133
- Acronym / sponsor ID
- IN-US-337-2116
- Conditions
- Hematopoietic Stem Cell Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to find eligible patients with untreated hepatitis C virus.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Kaiser PermanenteUniversity, hospital or other
- Collaborators
- City of Hope National Medical Center
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 16 Feb 2018 (actual)
- Study completion
- 29 Apr 2018 (actual)
- First posted
- 12 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| LDV/SOF for 12 weeks. | Experimental | Drug: Ledipasvir 90mg/Sofosubvir 400mgLedipasvir 90mg/Sofosubvir 400mg fixed-dose combination (FDC) tablet for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Participant must be male or female at least 18 years of age at time of screening
- Participant must be able to provide written Informed Consent
- Participant must be able to adhere to study visit/procedure schedule and protocol requirements
- Time available (at least 12 weeks) for treatment of hepatitis C prior to autologous or allogeneic transplantation
- First autologous or allogeneic HCT and hematologic disease in remission on initiation of antiviral therapy for hepatitis C infection
Key exclusion criteria (17 listed)
- Participant unwilling to provide written informed consent
- Participant unwilling to adhere to study visit/procedure schedule and protocol requirements
- Participant is pregnant or is a breastfeeding female
- Positive test result for hepatitis B surface antigen (HBsAG), hepatitis B core antibody (HBcAb), or confirmed positive anti-HIV antibody test
- Received study contraindicated medications prior to study drug administration including but not limited to those listed in the Full Prescribing Information Sheet for ledipasvir/sofosbuvir (Harvoni®).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ledipasvir 90mg/Sofosubvir 400mgAlso: HarvoniLedipasvir 90mg/Sofosubvir 400mg (LDV/SOF) FDC is to be administered once daily with or without food for12 weeks. | Drug | LDV/SOF for 12 weeks. |
Primary outcome
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.
5 secondary outcomes
Rate of HCV Relapse Post HCT
Time frame: 2 Years
Effect of Virologic Suppression on Post HCT Complications
Time frame: 2 Years
Proportion of Patients with Sustained Virologic Response at Time of Transplant
Time frame: 2 Years
Cumulative Incidence of HCV Relapse
Time frame: 2 Years
Progression of Liver Fibrosis After Transplant
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amandeep Sahota, MD principal investigator
Kaiser Permanente
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ledipasvir 90mg/Sofosubvir 400mg in people with Hematopoietic Stem Cell Transplantation, run by Kaiser Permanente at 2 sites 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 18 inclusion and 17 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: withdrawn, as of the sponsor's last update on 31 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Safety and Tolerability of LDV/SOF Treatment in Candidates for HCT with hepatitis C infection (time frame: 2 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Aug 2018.