Efficacy of immunotherapy with TG4040, peg-interferon, and ribavirin in a Phase 2 study of patients with chronic HCV infection

Gastroenterology. 2014 Jul;147(1):119-131.e3. doi: 10.1053/j.gastro.2014.03.007. Epub 2014 Mar 18.

Abstract

Background & aims: TG4040 is a modified vaccinia Ankara (MVA) virus that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B. We performed a phase II open-label study to determine the efficacy, safety, and immunotherapeutic properties of TG4040 in combination with pegylated interferon α-2a and ribavirin (PEG-IFNα/RBV) in patients with chronic HCV infection.

Methods: Treatment-naive patients with HCV genotype 1 infection were assigned randomly to 1 of the following groups: PEG-IFNα/RBV for 48 weeks (group A, n = 31), PEG-IFNα/RBV for 4 weeks followed by PEG-IFNα/RBV for 44 weeks with 6 injections of TG4040 (group B, n = 63), or TG4040 for 12 weeks (7 injections) followed by PEG-IFNα/RBV for 48 weeks with 6 injections of TG4040 (group C, n = 59). The primary end point was complete early virologic response (cEVR), defined as HCV-RNA level less than 10 IU/mL after 12 weeks of PEG-IFNα/RBV treatment.

Results: In group C, 64.2% of evaluable patients achieved cEVR, compared with 30.0% in group A and 45.9% in group B (P = .0003 for group C vs A). A higher percentage of patients achieved a sustained virologic response 24 weeks after therapy ended in group C (58.2%) than in groups A (48.4%) or B (50.8%). HCV- and MVA-specific T-cell responses were observed predominantly in group C. As expected, most patients given injections of TG4040 developed anti-MVA antibodies. The combination of TG4040 and PEG-IFNα/RBV was reasonably well tolerated. However, PEG-IFNα-associated thrombocytopenia developed in 3 patients who carried the class II HLA allele DRB01*04.

Conclusions: A higher percentage of patients with chronic HCV infection who received immunotherapy with TG4040 followed by TG4040 and PEG-IFNα/RBV achieved a cEVR compared with patients who received only PEG-IFNα/RBV therapy. These findings show that immunotherapies that activate T cells are effective in patients with chronic HCV infection. ClinicalTrials.gov number, NCT01055821.

Keywords: ELISpot; Immune Response; SVR24; Vaccine.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Anti-Idiotypic / metabolism
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology
  • Humans
  • Immunotherapy* / adverse effects
  • Interferon-alpha / adverse effects
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Ribavirin / adverse effects
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use*
  • Treatment Outcome
  • Viral Vaccines / adverse effects
  • Viral Vaccines / pharmacology
  • Viral Vaccines / therapeutic use*

Substances

  • Antibodies, Anti-Idiotypic
  • Antiviral Agents
  • Interferon-alpha
  • MVA vaccine
  • Recombinant Proteins
  • Viral Vaccines
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT01055821