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Efficacy of Immunotherapy With TG4040, Peg-Interferon, and Ribavirin in a Phase 2 Study of Patients With Chronic HCV Infection

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Titel: Efficacy of Immunotherapy With TG4040, Peg-Interferon, and Ribavirin in a Phase 2 Study of Patients With Chronic HCV Infection
Autoren: Vicente Carreño, Adrian M. Di Bisceglie, Patricia Zerr, Manuel Romero Gomez, Coman Tănăsescu, Ewa Janczweska–Kazek, Geneviève Inchauspé, Jean Marc Limacher, Heiner Wedemeyer, Włodzimierz Mazur, Delphine Agathon, François Habersetzer, Marie Hennequi, Géraldine Honnet, Robert Flisiak, Carol Stanciu, Vincent Bataille, Alexander Fich, Myew–Ling Toh
Quelle: Gastroenterology. 147:119-131.e3
Verlagsinformationen: Elsevier BV, 2014.
Publikationsjahr: 2014
Schlagwörter: Male, 0301 basic medicine, chronic - drug therapy, Polyethylene glycols - pharmacology, Viral vaccines - therapeutic use, Antiviral agents - adverse effects, Recombinant proteins - adverse effects, Hepacivirus, Polyethylene Glycols, chronic - immunology, Interferon-alpha - adverse effects, Immunotherapy - adverse effects, Vaccines, DNA, Treatment outcome, Middle aged, Interferon-alpha - pharmacology, Polyethylene glycols - adverse effects, Polyethylene glycols - therapeutic use, Viral vaccines - pharmacology, anti-idiotypic - metabolism, Middle Aged, Hepatitis C, Recombinant Proteins, Antibodies, Anti-Idiotypic, 3. Good health, Treatment Outcome, Drug Therapy, Combination, Female, Drug therapy, Immunotherapy, Adult, Viral vaccines - adverse effects, Genotype, Antiviral agents - therapeutic use, Recombinant proteins - therapeutic use, Ribavirin - pharmacology, Antiviral Agents, Antibodies, Interferon-alpha - therapeutic use, 03 medical and health sciences, Recombinant proteins - pharmacology, Ribavirin, Humans, Aged, combination, chronic - genetics, Interferon-alpha, Viral Vaccines, Hepatitis C, Chronic, Ribavirin - therapeutic use, Hepacivirus - drug effects, Antiviral agents - pharmacology, Ribavirin - adverse effects
Beschreibung: 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.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.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.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.
Publikationsart: Article
Sprache: English
ISSN: 0016-5085
DOI: 10.1053/j.gastro.2014.03.007
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/24657484
https://www.gastrojournal.org/article/S0016-5085(14)00356-4/pdf
https://www.sciencedirect.com/science/article/pii/S0016508514003564
https://pubmed.ncbi.nlm.nih.gov/24657484/
https://www.gastrojournal.org/article/S0016-5085(14)00356-4/fulltext
https://www.ncbi.nlm.nih.gov/pubmed/24657484
Rights: Elsevier TDM
Dokumentencode: edsair.doi.dedup.....e5fbfb6fa4116cafe60a34612763a2cc
Datenbank: OpenAIRE
Beschreibung
Abstract: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.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.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.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.
ISSN:00165085
DOI:10.1053/j.gastro.2014.03.007