1403 SIGNIFICANT IMPROVEMENT OF COMPLETE EVR IN HCVAC PHASE II CLINICAL TRIAL WHEN ADDING TG4040 THERAPEUTIC VACCINE TO PEGIFNα2A AND RIBAVIRIN

Wedemeyer, Heiner; Janczewska, Ewa; Wlodzimierz, M.; Stanciu, C; Habersetzer, F.; Carréño, Vicente; Bisceglie, Adrian M. Di; Tănăsescu, C; Flisiak, Robert; Romero-Gómez, María Pilar; Fich, Alexander; Zemmour, Christophe; Fournillier, Anne; Zerr, Philippe; Agathon, Delphine; He, Huiling; Bonnefoy, Jean‐Yves; Inchauspe, F.; Limacher, Jean Marc

doi:10.1016/s0168-8278(12)61414-7

Cited by 5 publications

(7 citation statements)

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“… 72 Comparing the results with other vaccine candidates, in the case of IC-41, 73 which failed to prevent relapse in the study group. and TG4040 (Transgene, France), in a Phase II trial 74 we were able to reduce HCV viral load to approximately 0.5 log IU/mL. Although those results were attributed by the authors to the vaccine candidate, criteria described elsewhere 66 suggest that the resulting changes in viral load should be >1 log IU/mL to be considered as secondary to therapeutic intervention.…”

Section: Discussionmentioning

confidence: 73%

Clinical Evaluation of Terap C Vaccine in Combined Treatment with Interferon and Ribavirin in Patients with Hepatitis C

Guridi

Fernández

Dueñas‐Carrera

et al. 2017

Current Therapeutic Research

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BackgroundAn estimated 170 million individuals worldwide are infected with the hepatitis C virus (HCV). Although treatment options using a combination of pegylated interferon and ribavirin (P-IFN/RBV) are available, sustained clearance of the virus is only achieved in approximately 40% of individuals infected with HCV genotype 1. Recent advances in the treatment of HCV using directly acting antiviral agents have been achieved; however, treatment can be very expensive and is associated with substantial side effects. The development of a new treatment modality is needed. One possible modality could be specific immunotherapy. Terap C is a therapeutic vaccine candidate composed of pIDKE2, a plasmid expressing HCV structural antigens, with a recombinant HCV core protein, Co.120.ObjectiveTo assess the safety and efficacy of concomitant therapy with the candidate vaccine, Terap C, IFN α-2b and ribavirin in untreated individuals with HCV genotype 1 infection.MethodsThis was a Phase II randomized, placebo-controlled, double-blind clinical trial evaluating the safety and efficacy of Terap C concomitant with IFN α-2b/RBV in 92 treatment-naïve patients with HCV genotype 1 infection. The study was conducted at the Gastroenterology Institute in Havana, Cuba. Patients were randomly assigned to 1 of 5 groups. The control group (Group 1) received IFN α-2b/RBV and placebo for 48 weeks. Groups 2 and 3 were administered Terap C 6 and 9 times, respectively, in addition to standard IFN α-2b/RBV treatment. In groups 4 and 5, Terap C was introduced 12 weeks after the initiation of IFN α-2b/RBV and administered 6 and 9 times, respectively, concomitant with IFN α-2b/RBV.ResultsAll patients showed some adverse events. Out of 3615 adverse events, only 18.8% were considered to be probably associated with administration of Terap C. Most events (47.4%) were considered to be improbably associated with of administration Terap C. Only 33.8% were considered possibly temporarily associated with Terap C, and can be explained by the use of conventional IFN α-2b + RBV or by HCV itself. The most common adverse events (≥65%) observed were pain at the injection site, headache, asthenia, psychiatric disturbances, fever, and gastrointestinal symptoms. Regarding sustained virological response, a 20% superiority was observed in the patients who received concomitant Terap C treatments from the beginning of the study compared with those who started after Week 12.ConclusionsVaccination with Terap C in patients with chronic HCV infection was safe and well tolerated. Clinical trial protocol code: IG/VHI/HC/0701; Public Register Code: RPCEC00000074.

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Section: Discussionmentioning

confidence: 73%

Clinical Evaluation of Terap C Vaccine in Combined Treatment with Interferon and Ribavirin in Patients with Hepatitis C

Guridi

Fernández

Dueñas‐Carrera

et al. 2017

Current Therapeutic Research

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“…GI-5005 is not able to increase SVR compared to PR alone, except in a subgroup of difficult-to-treat patients. Other vaccines, such as ChronVac-C, IC41, and TG-4040, demonstrate limited antiviral activity 30,58. Polyclonal and monoclonal antibodies do not reach any endpoint in trials evaluating recurrence after liver transplantation.…”

Section: Treatment Of Gt-1 Patients Beyond Boceprevir and Telaprevirmentioning

confidence: 99%

“…Other vaccines, such as ChronVac-C, IC41, and TG-4040, demonstrate limited antiviral activity. 30 , 58 Polyclonal and monoclonal antibodies do not reach any endpoint in trials evaluating recurrence after liver transplantation. Toll-like receptors may enhance the host immune system against HCV; they are currently in the early development phase.…”

Section: Treatment Of Gt-1 Patients Beyond Boceprevir and Telaprevirmentioning

confidence: 99%

Chronic hepatitis C: future treatment

Wendt¹,

Adhoute²,

Castellani³

et al. 2014

CPAA

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The launch of first-generation protease inhibitors (PIs) is a major step forward in HCV treatment. However, the major advance is up to now restricted to genotype 1 (GT-1) patients. The development of second-wave and second-generation PIs yields higher antiviral potency through plurigenotypic activity, more convenient daily administration, fewer side effects and, for the second-generation PIs, potential activity against resistance-associated variants. NS5B inhibitors include nucleoside/nucleotide inhibitors (NIs) and non-nucleotide inhibitors (NNIs). NIs have high efficacy across all genotypes. Sofosbuvir has highly potent antiviral activity across all genotypes in association with pegylated interferon and ribavirin (PR), thus allowing shortened treatment duration. NS5A inhibitors (NS5A.I) have highly potent antiviral activity. It has recently been shown for the first time that NS5A.I in combination with protease inhibitors can cure GT-1b null responders in an interferon-free regimen. Besides, several studies demonstrate that interferon (IFN)-free regimens with direct-acting antiviral agent combinations are able to cure a large number of either naïve or treatment-experienced GT-1 patients. Moreover, quadruple regimen with PR is able to cure almost all GT-1 null responders. The development of pan-genotypic direct-acting antiviral agents (NIs or NS5A.I) allows new combinations with or without PR that increase the rate of sustained virological response for all patients, even for those with cirrhosis and independently of the genotype. Therefore, the near future of HCV treatment looks promising. The purpose of this article is to provide an overview of the clinical results recently reported for HCV treatment.

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“… 66 Recently, Transgene's report of a phase II clinical trial showed that pre-treatment of HCV-infected patients with the vaccine prior to treatment with INF-α and ribavirin increased the early virological response (64% versus 30% in the control group). 67 However, significant side effects of this combined therapy have been reported rendering this regimen potentially problematic. Okarios is conducting a phase Ib trial using the prime/boost method with replication defective adenovirus 6 and modified vaccinia Ankara expressing the HCV NS3, NS4a, NS4b, NS5a and NS5b genes in concert with standard-of-care drug therapy.…”

Section: Therapeutic Vaccinementioning

confidence: 99%

Progress towards a hepatitis C virus vaccine

Law

Landi

Magee

et al. 2013

Emerging Microbes & Infections

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New drugs to treat hepatitis C are expected to be approved over the next few years which promise to cure nearly all patients. However, due to issues of expected drug resistance, suboptimal activity against diverse hepatitis C virus (HCV) genotypes and especially because of their extremely high cost, it is unlikely that these HCV drugs will substantially reduce the world's HCV carrier population of around 170 million in the near future or the estimated global incidence of millions of new HCV infections. For these reasons, there is an urgent need to develop a prophylactic HCV vaccine and also to determine if therapeutic vaccines can aid in the treatment of chronically infected patients. After much early pessimism on the prospects for an effective prophylactic HCV vaccine, our recent knowledge of immune correlates of protection combined with the demonstrated immunogenicity and protective animal efficacies of various HCV vaccine candidates now allows for realistic optimism. This review summarizes the current rationale and status of clinical and experimental HCV vaccine candidates based on the elicitation of cross-neutralizing antibodies and broad cellular immune responses to this highly diverse virus.

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1403 SIGNIFICANT IMPROVEMENT OF COMPLETE EVR IN HCVAC PHASE II CLINICAL TRIAL WHEN ADDING TG4040 THERAPEUTIC VACCINE TO PEGIFNα2A AND RIBAVIRIN

Cited by 5 publications

References 0 publications

Clinical Evaluation of Terap C Vaccine in Combined Treatment with Interferon and Ribavirin in Patients with Hepatitis C

Clinical Evaluation of Terap C Vaccine in Combined Treatment with Interferon and Ribavirin in Patients with Hepatitis C

Chronic hepatitis C: future treatment

Progress towards a hepatitis C virus vaccine

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