Heart Failure, Hepatitis C, Chronic, Lung Diseases, Interstitial, Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
This is a multicenter study in Hepatitis C Virus (HCV) infected adult patients who also have advanced cardiac disease or advanced lung disease.
Detailed description
This is a multicenter study in HCV infected adult patients who also have either advanced cardiac disease, or advanced lung disease. Advanced cardiac disease is defined as a marked limitation of physical activity, or discomfort upon physical activity. The patients in the advanced cardiac disease group must also have been hospitalized for heart failure within the last 12 months. Advanced lung disease is defined as patients who have been diagnosed with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD). Patients in the COPD group must have abnormalities in their forced expiratory volume (FEV) test, which measures the amount of air exhaled. They may or may not need supplemental oxygen. Patients in the ILD group must have been diagnosed with ILD and require supplement oxygen at all times.
Interventions
DRUGSofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC)
1 pill once daily of SOF/LDV FDC
Sponsors
Gilead Sciences
Duke University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic HCV Infection of Genotype 1, 4, 5, or 6 * HCV RNA \> 103 IU/mL at screening * 18 years of age or older * Diagnosis of chronic HCV infection, defined as positive HCV antibody or HCV RNA more than 6 months prior to screening OR an assessment of fibrosis F2 or greater prior to screening. Subjects in the advanced heart failure cohort must meet all HCV criteria, and all of the following criteria: * New York Heart Association (NYHA) Class III or IV functional classification * NYHA Class III: Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain. * NYHA Class IV: Patient with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. * ejection fraction ≤ 30% * hospitalized for heart failure in last 12 months Subjects in the advanced lung disease cohort must have been diagnosed with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) must meet all HCV criteria, and meet the following criteria for COPD or ILD: * ILD criteria: diagnosis of interstitial lung disease with chronic supplemental oxygen requirement at rest and/or with exertion. * COPD criteria (one of the following): * Forced expiratory volume (FEV1)\< 30% predicted * OR any FEV1 with chronic supplemental oxygen requirement at rest and/or with exertion * OR any FEV1 with chronic hypercapnia (baseline partial pressure of arterial carbon dioxide \[PaCO2\] \> 45)
Exclusion criteria
* Chronic HCV Infection with Genotype 2 or 3 * Treatment with any of the following agents * Amiodarone. Subjects previously treated with amiodarone must have stopped the amiodarone at least 60 days prior to day 1 of SOF/LDV FDC * Carbamazepine, phenytoin, phenobarbital, oxcarbazepine * Rifabutin, rifampin or rifapentine * HIV regimens containing tenofovir or tipranavir/ritonavir * St. John's wort * Rosuvastatin * Have any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance * History of hepatic encephalopathy or variceal hemorrhage * Hepatitis B surface antigen positive * Abnormal hematological and biochemical parameters, including: * Hemoglobin (Hb) \< 8 g/dL * Platelets ≤ 50,000/mm3 * alanine aminotransferase (ALT), aspartase aminotransferase (AST), or alkaline phosphatase ≥ 10 times upper limit of normal(ULN) * Total bilirubin \> 3 mg/dl * Severe renal impairment creatinine clearance (CrCl), i.e. \< 30 mL/min. * History of major organ transplantation with an existing functional graft. * History of clinically-significant drug allergy to nucleoside/nucleotide analogs. * Pregnant women or women planning to become pregnant * Women who are breastfeeding * Active or recent history (≤ 1 year) of drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Completed 24 Weeks of Therapy | 24 weeks | The primary safety endpoint is the number of subjects who complete a full course of therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Sustained Virologic Response (SVR) 12 | 12 weeks after completing treatment | The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 12 weeks after completing therapy. |
| Number of Subjects With Sustained Virologic Response (SVR) 4 | 4 weeks after completing treatment | The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 4 weeks after completing treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Discontinuation for Adverse Events and Serious Adverse Events | 12 weeks after completing treatment | Assessment for discontinuation due to adverse events and serious adverse events, as addressed by adverse events and laboratory tests. Final study visit is 12 weeks after treatment. |
Countries
United States
Participant flow
Recruitment details
Between 12/2016 and 12/2018, 15 subjects with chronic HCV and advanced heart failure or chronic HCV and lung disease were enrolled across 4 sites (academic medical centers in the US). Subjects all have genotype 1, 4, 5 or 6 HCV.
Participants by arm
| Arm | Count |
|---|---|
| Heart Failure Cohort Harvoni (sofosbuvir/ledipasvir fixed dose combination)
1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV)
Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC | 10 |
| Lung Disease Cohort Harvoni (sofosbuvir/ledipasvir fixed dose combination)
1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir
Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC | 5 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Heart Failure Cohort | Total | Lung Disease Cohort |
|---|---|---|---|
| Age, Continuous | 60.4 years STANDARD_DEVIATION 7.5 | 60.1 years STANDARD_DEVIATION 6.6 | 59.4 years STANDARD_DEVIATION 5.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 15 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 10 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 2 Participants |
| Region of Enrollment United States | 10 Participants | 15 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 5 |
| other Total, other adverse events | 0 / 10 | 0 / 5 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 |
Outcome results
Primary
Number of Subjects Who Completed 24 Weeks of Therapy
The primary safety endpoint is the number of subjects who complete a full course of therapy.
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Heart Failure Cohort | Number of Subjects Who Completed 24 Weeks of Therapy | 0 Participants |
| Lung Disease Cohort | Number of Subjects Who Completed 24 Weeks of Therapy | 1 Participants |
Secondary
Number of Subjects With Sustained Virologic Response (SVR) 12
The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 12 weeks after completing therapy.
Time frame: 12 weeks after completing treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Heart Failure Cohort | Number of Subjects With Sustained Virologic Response (SVR) 12 | 10 Participants |
| Lung Disease Cohort | Number of Subjects With Sustained Virologic Response (SVR) 12 | 3 Participants |
95% CI: [59.5, 98.3]
Secondary
Number of Subjects With Sustained Virologic Response (SVR) 4
The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 4 weeks after completing treatment.
Time frame: 4 weeks after completing treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Heart Failure Cohort | Number of Subjects With Sustained Virologic Response (SVR) 4 | 8 Participants |
| Lung Disease Cohort | Number of Subjects With Sustained Virologic Response (SVR) 4 | 3 Participants |
Other Pre-specified
Discontinuation for Adverse Events and Serious Adverse Events
Assessment for discontinuation due to adverse events and serious adverse events, as addressed by adverse events and laboratory tests. Final study visit is 12 weeks after treatment.
Time frame: 12 weeks after completing treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Heart Failure Cohort | Discontinuation for Adverse Events and Serious Adverse Events | 0 Participants |
| Lung Disease Cohort | Discontinuation for Adverse Events and Serious Adverse Events | 0 Participants |