Study of A Combination Pill With GS-7977 and GS-5885 for Hepatitis C in People With HIV
Condition: Hepatitis C; HIV
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: GS-7977/GS- 5885 FDC
Intervention description: 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.
Intervention MeSH terms: Sofosbuvir; Ledipasvir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Direct Acting Antiviral; Treatment Naive; Interferon Sparing; Ribavirin Sparing

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.
    

Eligibility 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 exclusion criteria are not to be enrolled in this
        study:

          1. Current or prior history of any of the following:

               1. Clinically significant illness (other than HCV) or any other major medical
                  disorder that may interfere with subject treatment, assessment or compliance with
                  the protocol; subjects currently under evaluation for a potentially
                  clinically-significant illness (other than HCV) are also excluded.

               2. Gastrointestinal disorder or post-operative condition that could interfere with
                  the absorption of the study drug.

               3. Poor venous access interfering with required study blood collection.

               4. Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal
                  hemorrhage).

               5. Solid organ transplantation.

               6. Significant pulmonary disease, significant cardiac disease or porphyria.

               7. Unstable psychiatric disease (Subjects with psychiatric illness that is
                  well-controlled on a stable treatment regimen or currently not requiring
                  medication may be included).

               8. Any malignancy or its treatment that in the opinion of the PI may cause ongoing
                  interference with host immunity; subjects under evaluation for malignancy are not
                  eligible.

               9. Significant drug allergy (such as anaphylaxis or hepatotoxicity).

              10. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson s
                  disease, alfa-1 antitrypsin deficiency, cholangitis).

              11. Patients with renal impairment or uncontrolled medical problems that could place
                  them at high risk for developing renal impairment.

          2. Positive test at screening for either HBsAg or quantifiable HBV DNA (completed only if
             necessary to rule out chronic HBV)

          3. Current use of non-protocol approved ARVs.

          4. A new AIDS-defining condition diagnosed within 30 days prior to screening or active,
             serious infection (other than HIV or HCV) requiring parenteral antibiotics, antivirals
             or antifungals within 30 days prior to Day 0.

          5. Cirrhosis of the liver

          6. Screening or baseline ECG with clinically significant ECG findings.

          7. Abnormal hematological and biochemical parameters, including:

               1. Neutrophil count < 750 cells/mm(3)

               2. Hemoglobin < 9 g/dL. If Hgb is < 11g/dL in women or < 12 g/dL in men. Other
                  causes of anemia should be excluded as medically indicated.

               3. Platelet count less than or equal to 50,000 cells/mm(3)

               4. Estimated GFR (calculated by the CKD-EP(I) equation) < 50 mL/min/per 1.73 m(2) if
                  not on ARV or < 60 mL/min if on ARVs

               5. ALT or AST greater than or equal to 10 times ULN

               6. Serum lipase greater than or equal to 1.5 times ULN (at screening or during the
                  screening period)

               7. Direct bilirubin greater than or equal to 1.50 times ULN

               8. Albumin less than or equal to 3.0 g/dL

               9. INR greater than or equal to 1.5 times ULN unless subject has known hemophilia or
                  is stable on an anticoagulant regimen affecting INR.

          8. Donation or loss of more than 400 mL blood within 8 weeks prior to first dose
             administration.

          9. Poorly controlled diabetes mellitus indicated by hemoglobin A1C > 10% at screening for
             known diabetics.

         10. Known hypersensitivity to, GS-5885, GS-7977, or formulation excipients.

         11. Pregnant/Breastfeeding women.

         12. Co-enrollment in other clinical trials is restricted, and requires approval of the
             Investigator.

             Study staff should be notified of co-enrollment status.

         13. Need for use of the following medications from 21 days prior to the start of study
             drugs through the end of treatment:

               1. Hematologic stimulating agents (e.g. erythropoiesis-stimulating agents (ESAs);
                  granulocyte colony stimulating factor (GCSF); thrombopoietin (TPO) mimetics)

               2. Chronic systemic immunosuppressants including, but not limited to,
                  corticosteroids (prednisone equivalent of > 10 mg/day for > 2 weeks),
                  azathioprine, or monoclonal antibodies (e.g., infliximab)

               3. Investigational agents or devices for any indication

               4. Medications for disease conditions excluded from the protocol (e.g., active
                  cancer, transplantation) are not listed under this Concomitant Medication section
                  and are disallowed in the study.

               5. Concomitant use of certain medications or herbal/natural supplements per PI
                  discretion expected to result in pharmacokinetic interactions resulting in
                  increases or decreases in exposure of study drug(s) as listed in Table of this
                  protocol.