Hepatitis C Treatment Naive Genotype 1 Consensus Interferon Trial
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Study type: Interventional
Phase: Phase 3

Summary: 
      Data have suggested that consensus interferon (CIFN) has greater antiviral activity in vitro
      compared with interferon alfa-2a or alfa-2b. Several clinical studies also suggest that CIFN
      has greater antiviral activity in patients with genotype 1 hepatitis C infection,
      particularly if given as a daily injection. These data indicate that the use of a regimen of
      daily CIFN and ribavirin will lead to greater virologic response rates compared with
      pegylated interferon alfa-2b and ribavirin in patients with genotype 1 infection, with
      comparable adverse events. Emerging data indicate that HCV genotype 1 patients with a delayed
      virologic response to initial therapy may benefit from an extended duration of therapy.
      Therefore, the goals of this pilot study are to determine the tolerability and efficacy of
      daily CIFN plus ribavirin when given for 52 weeks or an extended duration of therapy. The
      target population will consist of "difficult-to-treat" patients, defined as having the
      following characteristics: genotype 1, a North American patient population, predominantly
      male gender, and no specific exclusions for pre-existing psychiatric or substance abuse
      co-morbidities.
    

Detailed description: 
      Current treatment for hepatitis C is a pegylated interferon alfa plus ribavirin. This
      treatment is inadequate for patients with HCV genotype 1, since the majority of patients do
      not respond (termed non-responders) or respond but relapse (termed relapsers) following
      termination of these treatments. Data from the Veterans Health Administration (VHA) Hepatitis
      C Registry and community hospitals indicate that the large majority of patients identified
      with hepatitis C have characteristics associated with a poor treatment response and remain
      untreated at this time. Data have suggested that consensus interferon (CIFN, CIFN or
      interferon alfacon-1) has greater antiviral activity in vitro compared with interferon
      alfa-2a or alfa-2b. Preliminary data indicate that more patients with genotype 1 can respond
      to CIFN and ribavirin than current standard treatments, due to the fact that approximately
      25% of patients who are nonresponders to pegylated interferon and ribavirin may have a
      sustained response to a regimen of daily CIFN and ribavirin. Furthermore, difficult to treat
      patients may benefit from a longer duration of therapy than the standard 48 week regimen
      based on when an initial virologic response to therapy occurs.

      Aims: To determine the safety and efficacy of (A) daily CIFN (15 mcg/d sq) and ribavirin
      (1-1.2 gm/d PO) given for 52 weeks, vs (B) daily CIFN (15 mcg/d sq) and ribavirin (1-1.2 gm/d
      PO) given for 52 to 72 weeks for treatment-naïve patients with hepatitis C genotype 1, with
      treatment duration based on the virologic response during the initial 24 weeks.

      Methods: Patients who meet eligibility criteria will be stratified by race and randomized to
      one of two treatment arms, and all patients will have viral kinetics measured by quantitative
      PCR at weeks 4,8,12,16,20 and 24. Patients in treatment arm A will follow "standard" stopping
      rules, i.e., if there is not a 2-log drop in viremia by 12 weeks the treatment will be
      discontinued, otherwise they will all receive 52 weeks of treatment if they also are
      qualitative PCR negative by week 24. In treatment arm B the patients will be monitored
      monthly until they have a virologic response (defined as >2 log drop in viral levels from
      baseline) by quantitative PCR for up to 24 weeks. Once they have a virologic response by
      quantitative PCR their treatment will be continued for an additional 48 weeks. In both
      groups, treatment will be stopped if the patients do not become negative for HCV RNA by
      qualitative PCR by 24 weeks on therapy. A total of 192 patients at up to 10-20 sites will be
      recruited. The primary endpoint would be the number who achieve a sustained virologic
      response; secondary endpoints are the percentage of patients who complete therapy, have
      significant adverse events, and the relationship of early virologic response at each 4 week
      period between 4 and 24 weeks and those who achieve a sustained virologic response.

      Sample size determination: To detect an absolute difference of 20% or more in sustained
      virologic response between treatment arms A and B; the Log-rank test is performed at the
      alpha level of .05 and the test is maintained at least 80 percent statistical power; it is
      estimated that a total of 96 patients in each treatment arm will be required.

      Analysis: Univariate and multivariate analysis will be used to determine factors associated
      with final endpoints. Subgroup analyses will be done based on time to early virologic
      response and duration of therapy each stratification. The primary and secondary endpoints
      will be determined on an intention-to-treat basis starting with all patients that receive at
      least one dose of study medications. The primary and secondary endpoints will also be
      determined in a per-protocol analysis on those patients who take 80% of the prescribed CIFN
      and 80% of the prescribed ribavirin for 80% of the time.

      Significance: The current initial treatment of pegylated interferon alfa and ribavirin for
      patients with hepatitis C who are genotype 1 and have other "difficult-to-treat"
      characteristics is inadequate. The results of this trial are needed to demonstrate the safety
      and efficacy of two regimens of daily CIFN and ribavirin. Since the large majority of
      hepatitis C patients in VA and other community hospitals fall into this category, the results
      of this trial may influence the potential treatments recommended for these patients.
    

Intervention name(s): consensus interferon (Interferon Alfacon-1) and ribavirin; Consensus Interferon alfa (CIFN) and ribavirin
Intervention type(s): Drug; Drug
Intervention description(s): CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B); CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B)
Other intervention name(s): interferon alfacon-1; interferon alfacon-1
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alfacon-1
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hepatitis C; interferon alfa; ribavirin; interferon alfacon-1; antiviral therapy