Hepatitis C, HIV
Conditions
Keywords
Direct Acting Antiviral, Treatment Naive, Interferon Sparing, Ribavirin Sparing
Brief summary
Background: \- Present treatment for hepatitis C includes the use of a weekly injection and two different pills. This treatment is associated with serious side effects. Drugs that can be taken by mouth and cure HCV infection without serious side effects would be a great help to the large number of people infected with HCV. GS-7977 and GS-5885 are new medications being developed to treat the hepatitis C virus (HCV) infection. They are still being researched and are not approved by the Food and Drug Administration. They are being developed as treatment for hepatitis C as a single pill taken once a day. Objectives: \- To determine whether a combination of the two study drugs can safely and effectively treat HCV infection in people with HIV infection and who do not have cirrhosis of the liver. Eligibility: \- Individuals who have HIV infection and have liver disease caused by infection with HCV. Design: * Participants will be screened with a physical exam and medical history. Blood samples will be collected. Urine samples will be collected from participants who might become pregnant. If a participant has not had a liver biopsy in the past 3 years, one will be required. * Participants will take one pill daily for 12 weeks. This pill will be a combination of the two study drugs. * Treatment will be monitored with frequent clinic visits and blood tests over a total of 60 weeks.
Detailed description
Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the US an estimated 4.1 million people are infected with HCV which is the principal cause of death from liver disease and leading indication for liver transplantation. Significant advances have been made with the approval of directly acting antivirals (DAA) namely the protease inhibitors, telaprevir (TVR) and boceprevir (BOC) which have been shown to significantly improve rates of sustained virologic response (SVR). Response rates to these new combinations in HIV/HCV are also very promising, however treatment has been characterized with high rates of toxicities. Recently several trials have confirmed the efficacy of potent DAA therapy without concomitant IFN in the treatment of HCV monoinfected individuals. Given the improved response rates achieved with a combination of DAAs with fast HCV suppression and improved side-effect profiles; and the need for better therapy for HIV/HCV co-infected subjects, we propose a study to determine the safety, tolerability and efficacy of 12 weeks of treatment with a fixed dose combination of GS-7977 and GS-5885 in HIV/HCV Genotype 1 (GT-1) subjects. We hypothesize that anti-HCV therapy that does not rely on the host immune system will provide an enhanced rate of SVR among HIV/HCV GT-1 coinfected subjects. The findings from this study will aid in our understanding of determinants of response to an IFN-free regimen in HIV/HCV coinfected individuals.
Interventions
DRUGGS-7977/GS- 5885 FDC
The GS-7977/GS-5885 FDC product combines a potent HCV nucleotide inhibitor and a potent HCV NS5A inhibitor and will be given for 12 weeks.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: 1. Eighteen years of age or older at screening. 2. HCV treatment-naive, as defined as no prior exposure to any IFN, RBV, or other approved or experimental HCV-specific direct-acting antiviral agent. 3. Participants must be willing to practice either: 1. Abstinence from sexual intercourse or 2. At least 2 forms of contraception including one barrier method from 2 weeks prior to Day 0 through 30 days after the last dose is received. i. Female partners of male study subjects may rely upon hormonal contraception as one of the 2 methods; however female study subjects may not. 4. Chronic hepatitis C infection defined as one of the following: 1. Positive for anti-HCV antibody, HCV RNA, or an HCV genotype at least 6 months before screening, and positive for HCV RNA and anti-HCV antibody at the time of screening or 2. Positive for anti-HCV antibody and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of chronic hepatitis C disease, such as the presence of fibrosis). 5. HIV treatment status: 1. Documented HIV infection, ARV untreated for \> 8 weeks preceding dosing and having either: 1. a CD4 T-cell count greater than or equal to 500 cells/mm3 within 8 weeks of Day 0 or 2. an HIV viral load less than 500 copies/mL with a stable CD4 count for at least 3 months. 2. Documented HIV infection on a stable, protocol-approved, ARV regimen for greater than or equal to 8 weeks prior to dosing and is expected to continue the current ARV regimen through the end of study with all of the following: 1. a CD4 T-cell count \> 100 cells/mm3 2. a documented plasma HIV-1 RNA level less than the level of detection for at least 8 weeks preceding dosing. If the lower limit of detection of the local HIV-1 RNA assay is \< 50 copies/mL (e.g.,\< 20 copies/mL), the Screening plasma HIV-1 RNA level cannot exceed 50 copies/mL. 3. HIV ARV agents including only combination regimens consisting of medications from the following list: tenofovir (TDF), emtricitabine (FTC), efavirenz, raltegravir, and rilpivirine administered according to their manufacturer s prescribing information. (reference Section 10.3 for additional information) 6. Documentation of hepatitis C genotype 1a, 1b or mixed 1a/1b 7. Absence of cirrhosis, defined as one of the following: 1. A liver biopsy performed within 36 calendar months of screening showing absence of cirrhosis. 2. FibroTest score of \< 0.48 AND APRI of \< 1 performed during the 8 weeks preceding dosing (In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy is required). 8. Able to effectively communicate with the Investigator and other center personnel. 9. Willing to give written informed consent and comply with the study restrictions and requirements. 10. If opioid-dependent, subjects must be participating in a supervised treatment. 11. Participants must have a primary medical provider outside of OP8 and the NIH for medical management.
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Achieved SVR12 (HCV RNA <LLOQ 12 Weeks After Completion of Treatment) | 12 weeks after completion of treatment | The primary end point was sustained virologic response \[plasma HCV RNA level \<12 IU/mL by real-time HCV assay (Abbott)\] at 12 weeks after treatment completion (SVR12) among all patients enrolled in the study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subjects With HIV and HCV on Antiretroviral Agents Subjects with HIV and HCV on antiretroviral agents given 'Drug: GS-7977 (sofosbuvir 400mg)/GS-5885 (ledipasvir 90mg) FDC' once daily by mouth for 12 weeks. The GS-7977/GS-5885 product combines a potent HCV nucleotide inhibitor and a potent HCV NS5A inhibitor. | 37 |
| Subjects With HIV and HCV Who Are Not on Antiretroviral Agents Subjects with HIV and HCV who are not on antiretroviral agents given 'Drug: GS-7977 (sofosbuvir 400mg)/GS-5885 (ledipasvir 90mg) FDC' once daily by mouth for 12 weeks. The GS-7977/GS-5885 product combines a potent HCV nucleotide inhibitor and a potent HCV NS5A inhibitor. | 13 |
| Total | 50 |
Baseline characteristics
| Characteristic | Subjects With HIV and HCV on Antiretroviral Agents | Subjects With HIV and HCV Who Are Not on Antiretroviral Agents | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 0 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 13 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 13 Participants | 48 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 | 31 Participants | 10 Participants | 41 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 | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 30 Participants | 7 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 37 | 13 / 13 |
| serious Total, serious adverse events | 0 / 37 | 1 / 13 |
Outcome results
Primary
Percentage of Participants With Achieved SVR12 (HCV RNA <LLOQ 12 Weeks After Completion of Treatment)
The primary end point was sustained virologic response \[plasma HCV RNA level \<12 IU/mL by real-time HCV assay (Abbott)\] at 12 weeks after treatment completion (SVR12) among all patients enrolled in the study.
Time frame: 12 weeks after completion of treatment
Population: The analysis included all subjects who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With HIV and HCV on Antiretroviral Agents | Percentage of Participants With Achieved SVR12 (HCV RNA <LLOQ 12 Weeks After Completion of Treatment) | 97 percentage of participants |
| Subjects With HIV and HCV Who Are Not on Antiretroviral Agents | Percentage of Participants With Achieved SVR12 (HCV RNA <LLOQ 12 Weeks After Completion of Treatment) | 100 percentage of participants |