Sofosbuvir Plus Ribavirin Without Interferon For Treatment of Acute HCV in HIV-Infected Individuals (SWIFT-C)
Brief Summary: A5327 is an open-label, two cohort study, in which 44 acutely HCV infected HIV-1 positive subjects will be enrolled and administered oral sofosbuvir (SOF) in combination with weight based ribavirin (RBV). The first cohort, 17 subjects, will receive treatment for 12 weeks. The second cohort, 27 subjects, will receive treatment for 8 weeks if non-inferiority of the 12-week cohort is met or 12 weeks if not. We hypothesize that an interferon-sparing regimen of SOF and RBV can achieve a sustained virologic response 12 (SVR) rates that are non-inferior to the current SOC treatment for acute HCV in HIV/HCV coinfected individuals with an improved safety profile and with a shorter length of treatment.
Objectives: The primary objectives are to evaluate HCV treatment response to SOF and RBV taken for 12 or 8 weeks and to evaluate the safety and tolerability of this combination oral therapy for HCV.
The secondary objectives are as follows:
- To evaluate the antiviral efficacy of SOB and RBV as measured by the proportion of patients with undetectable HCV RNA at specified weeks during and post treatment.
- To assess the emergence of viral resistance to SOF when administered with RBV for acute HCV infection.
- To estimate RBV pharmacokinetics (PK) and evaluate covariates which may affect RBV PK.
- To assess the relationship of viral clearance and RBV PK with baseline predictors including genetic polymorphisms (e.g., IL28 and ITPA), expression of key host immune response genes and proteins.
- To evaluate subject adherence using several tools including RBV intracellular levels
- To assess how successful DAA based therapy alleviates type I IFN-induced immune dysfunction during acute HCV infection.
Inclusion/Exclusion Criteria: (Full I/E criteria can be found in section 4.0 of the protocol.)
The subjects must be 18 years of age or older and have HIV infection. They also must have documentation of new or re-infection of acute HCV infection (any genotype) within 6 months prior to entry. They should be on stable ARV’s (didanosine, stavudine zidovudine excluded) or based on your assessment does not require HIV therapy at this time. They cannot have had an investigational drug within 30 days prior to screening and never been exposed to direct-acting antiviral targeting the HCV NS5B polymerase.
Definition of Acute HCV infection and acute HCV re-infection is as follows:
Acute HCV infection will be defined as meeting one of the following criteria:
- New (<24 weeks prior to initial A5327 screening) ALT elevation to ≥ 5X ULN OR >250 U/L in subjects with documented normal ALT in the preceding 12 months or ≥ 10X ULN OR >500 U/L in subjects with abnormal or no measured ALT baseline in the preceding 12 months with positive HCV RNA excluding those with any prior positive anti-HCV
- Positive HCV RNA with prior negative anti-HCV or HCV RNA within the preceding 6 months
AND the following criterion:
- Negative anti-HAV IgM and anti-HBV core IgM as well as exclusion of other causes of acute hepatitis;
Acute re-infection will be defined as meeting one of the following criteria:
- New (<24 weeks prior to initial A5327 screening) ALT elevation to ≥ 5X ULN OR >250 U/L in subjects with documented normal ALT in the preceding 12 months or ≥ 10X ULN OR >500 U/L in subjects with abnormal or no measured ALT baseline in the preceding 12 months with positive HCV RNA
- Positive HCV RNA with prior negative HCV RNA within the preceding 6 months
AND both of the following:
- Documentation of clearance of prior infection either spontaneously or after treatment with two negative HCV RNA a minimum of 6 months apart AND
- Negative anti-HAV IgM and anti-HBV core IgM as well as exclusion of other causes of acute hepatitis.
Treatment: Study treatment is defined as oral sofosbuvir (SOF) in combination with weight based (WB) ribavirin (RBV). Cohort 1 will receive 400mg of SOF and WB RBV for 12 weeks. SOF is taken every morning with food and WB RBV is taken every morning and every night with food. Cohort 2 will receive 400mg SOF and WB RBV for 8 weeks. If cohort 1 does not meet non-inferiority criteria, cohort 2 will open for 12 weeks of treatment.
Duration of Study: Participants will be in this study for up to 36 weeks (8-12 weeks on-treatment followed by 24 weeks of follow-up)
For more information contact:Ericka R. Patrick, RN, MSN