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1. Results of a screening campaign for hepatitis C viral infection in a Brussels hospital : do we need to go further?

Author

UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Lanthier, N, Ruiz-Moreno, A, Dahlqvist, G, Delire, B, Stärkel, P, Horsmans, Y, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Lanthier, N, Ruiz-Moreno, A, Dahlqvist, G, Delire, B, Stärkel, P, and Horsmans, Y

Abstract

No abstract available

Published
2022

21. Ombitasvir/paritaprevir/ritonavir plus ribavirin for 24 weeks in patients with HCV GT4 and compensated cirrhosis (AGATE-I Part II)

Author

Asselah, Tarik, Alami, Negar Niki, Moreno, Christophe, Pol, Stanislas, Karatapanis, Stylianos, Gschwantler, Michael, Horsmans, Y., Elefsiniotis, Ioannis, Larrey, Dominique, Ferrari, Carlo, Rizzetto, Mario, Orlandini, Alessandra, Calleja, José Luís Uis J.L., Bruno, Savino, Schnell, Gretja, Qaqish, Roula R.B., Redman, Rebecca, Pilot-Matias, Tami, Kopecky-Bromberg, Sarah, Yu, Yao, Mobashery, Niloufar, Asselah, Tarik, Alami, Negar Niki, Moreno, Christophe, Pol, Stanislas, Karatapanis, Stylianos, Gschwantler, Michael, Horsmans, Y., Elefsiniotis, Ioannis, Larrey, Dominique, Ferrari, Carlo, Rizzetto, Mario, Orlandini, Alessandra, Calleja, José Luís Uis J.L., Bruno, Savino, Schnell, Gretja, Qaqish, Roula R.B., Redman, Rebecca, Pilot-Matias, Tami, Kopecky-Bromberg, Sarah, Yu, Yao, and Mobashery, Niloufar

Abstract

Background and Aims: AGATE-I Part I previously reported high sustained virologic response rates in hepatitis C genotype 4 patients with cirrhosis, with 12 and 16 weeks' treatment with a combination of two direct-acting antivirals, ombitasvir and paritaprevir (codosed with ritonavir), plus ribavirin. Part II, reported here, extended the trial to include a 24-week treatment arm to fully assess treatment duration in patients with chronic hepatitis C genotype 4 infection and compensated cirrhosis. Methods: Enrollment took place between June and November of 2015. Treatment-naive and interferon-experienced patients with chronic hepatitis C genotype 4 infection and compensated cirrhosis were enrolled into Arm C; patients previously treated with a sofosbuvir-based regimen were enrolled into Arm D. All patients received a 24-week treatment with ombitasvir, paritaprevir, and ritonavir plus ribavirin. The primary outcome was the proportion of patients with a sustained virologic response (hepatitis C virus RNA < 25 IU/mL) at posttreatment week 12 in the intention-to-treat population. The safety population included all patients who received at least one dose of study drug. Results: In total, 64 patients were enrolled into AGATE-I Part II. Sustained virologic response at posttreatment week 12 was achieved in 57 of 61 patients (93.4%; 97.5% confidence interval, 92.6-97.7) in Arm C and 3 of 3 patients (100%) in Arm D. Two patients were missing SVR12 data, and two prematurely discontinued treatment. The most common adverse events for Arm C were fatigue (16 [26%]) and asthenia (15 [25%]). Results were comparable with those reported in Part I. Conclusions: AGATE-I Part II indicates that extending treatment beyond 12 weeks in genotype 4–infected patients with compensated cirrhosis does not offer additional benefit., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

42. Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort

Author

GUARD C, Study Group, Hassanein, T, Bakalos, G, Ahlers, S, Shiffman, Ml, Tallarico, L, Reddy, Kr, Orlandini, A, Ferenci, P, Derbala, M, Coppola, C, Foster, Gr, Basho, J, Shabanaj, G, Harxhi, A, Debzi, N, Afredj, N, Guessab, N, Mahindad, N, Mahiou, H, Aissaoui, M, Al Qameesh, J, Al Ghandoor, Z, Assene, C, Bastens, B, Brixko, C, Cool, M, De Galocsy, C, Delwaide, J, George, C, Laukens, P, Lefebvre, V, Mulkay, Jp, Nevens, F, Servais, B, Van Vlierberghe, H, Horsmans, Y, Henrion, J, Sprengers, D, Michielsen, P, Bourgeois, S, Lasser, L, Langlet, P, Robaeys, G, Martinet, Jp, Warzee, P, Hoste, P, Reynaert, H, Juriens, I, Decaestecker, J, Van Der Meersch, F, Janssens, F, Ahmetagic, S, Verhaz, A, Bevanda, M, Calkic, L, Ibrahimpasic, N, Mesihovic, R, Mello, Ce, Ruiz, Fj, Martins Junior, E, Ferraz, Ml, Silva, G, Mendes, C, Lyra, A, Silva, Mh, Gomide, G, Fernandes, Jc, Pereira, P, Correa, Mc, Teixeira, R, Yousry, A, Hanno, A, Gabr, M, Omar, A, Esmat, G, Karatapanis, S, Nikolopoulou, V, Giannoulis, G, Manolakopoulos, S, Elefsiniotis, I, Drakoulis, C, Dimitroulopoulos, D, Kanatakis, S, Ketikoglou, I, Mimidis, K, Evgenidis, N, Akriviades, E, Vafiadi Zoubouli, I, Tsianos, E, Mela, M, Orfanou, E, Mousoulis, G, Karagiannis, I, Manesis, E, Varga, M, Nemesánszky, E, Fried, K, Schuller, J, Szalay, F, Lengyel, G, Tornai, I, Banyai, T, Lesch, M, Nagy, I, Gervain, J, Tusnadi, A, Schneider, F, Szentgyörgyi, L, Hunyady, B, Vincze, A, Tolvaj, G, Varkonyi, I, Makkai, E, Enyedi, J, Racz, I, Hausinger, P, Váczi, Z, Patai, Á, Ozsvár, Z, Lakner, L, Ribiczey, P, Bhalla, A, Somani, S, Luaia, R, Rao, P, Philip, M, Lawate, P, Nagral, A, Sood, A, Parikh, S, Merat, S, Nassiri Toosi, M, Alavian, Sm, Zali, Mr, Daryani, Ne, Drenaggi, D, Attili, Af, Bandiera, F, Bassi, P, Bellati, G, Bellantani, S, Brunetto, MAURIZIA ROSSANA, Bruno, S, Castelli, F, Castellacci, R, Cattelan, Am, Colombo, M, Craxi, A, D'Angelo, S, Colombo, S, Demelia, L, Di Perri, G, Di Giacomo, A, Ferrari, C, Francisci, D, Casinelli, K, Ganga, R, Costa, C, Mangia, A, Russo, Fp, Matarazzo, F, Mazzella, G, Mazzeo, M, Memoli, M, Montalbano, M, Montalto, G, Pieri, A, Passariello, N, Picciotto, A, Pietrangelo, A, Pirisi, M, Quirino, T, Raimondo, G, Rapaccini, Gl, Rizzardini, G, Rizzetto, M, Russello, M, Sabusco, G, Santantonio, T, Soardo, G, Amedea, A, Verucchi, G, Vinelli, F, Zignego, Al, Zuin, M, Ascione, A, Vinci, M, Pigozzi, Mg, Tundo, P, Saracco, Gm, Amoroso, P, Andreoni, M, Colletta, C, Erne, E, Megna, As, Biglino, A, Chiriaco, P, Foti, G, Spinzi, G, D'Amico, E, Paik, Sw, Ahn, Sh, Lee, Yn, Kim, Y, Yang, J, Han, Sy, Varghese, R, Al Gharabally, A, Askar, H, Sharara, A, Yaghi, C, Rached, Aa, Houmani, Z, Zaarour, F, Dohaibi, A, Ivanovski, L, Joksimovic, N, Abbas, Z, Memon, S, Mohsin, A, Masood, S, Hashmi, Z, Halota, W, Deron, Z, Mazur, W, Flisiak, R, Lipczynski, A, Musialik, J, Piekarska, A, Augustyniak, K, Baka Cwierz, B, Simon, K, Gietka, A, Berak, H, Sieklucki, J, Radowska, D, Szlauer, B, Piekos, T, Olszok, I, Jablkowski, M, Orszulak, G, Warakomska, I, Aleixo, Mj, Valente, C, Macedo, G, Sarmento Castro, R, Roxo, F, Faria, T, Mansinho, K, Velez, J, Ramos, Jp, Guerreiro, H, Alberto, S, Monteverde, C, Serejo, F, Peixe, P, Malhado, J, Curescu, M, Streinu Cercel, A, Caruntu, F, Livia, H, Preotescu, L, Arama, V, Ancuta, I, Gheorghe, L, Stanciu, C, Trifan, A, Acalovschi, M, Andreica, V, Pascu, O, Lencu, M, Sporea, I, Olteanu, D, Ionita Radu, F, Fierbinteanu Braticevici, C, Motoc, A, Silaghi, R, Musat, M, Coman, F, Stan, M, Cijevschi, C, Miftode, E, Delic, D, Jesic, R, Nozic, D, Svorcan, P, Fabri, M, Konstantinovic, L, Pelemis, M, Jankovic, G, Todorovic, Z, Nagorni, A, Kupcova, V, Skladany, L, Szantova, M, Krkoska, D, Jarcuska, P, Schreter, I, Oltman, M, Bocakova, J, Bunganic, I, Holoman, J, Giguere, A, Abdou, A. M., Basic (bio-) Medical Sciences, Gastroenterology, Laboratory of Molecullar and Cellular Therapy, Liver Cell Biology, Michielsen, Peter, GUARD-C Study Group, Graham R. Foster, Carmine Coppola, Moutaz Derbala, Peter Ferenci, Alessandra Orlandini, K. Rajender Reddy, Ludovico Tallarico, Mitchell L. Shiffman, Silke Ahler, Georgios Bakalo, Tarek Hassanein, GUARD-C Study Group: [.., Davide Drenaggi, Adolfo Francesco Attili, Franco Bandiera, Paolo Bassi, Giorgio Bellati, Stefano Bellantani, Maurizia Brunetto, Savino Bruno, Francesco Castelli, Roberto Castellacci, Anna Maria Cattelan, Massimo Colombo, Antonio Craxi, Salvatore D'angelo, Silvia Colombo, Luigi Demelia, Giovanni Di Perri, Antonio Di Giacomo, Carlo Ferrari, Daniela Francisci, Katia Casinelli, Roberto Ganga, Chiara Costa, Alessandra Mangia, Francesco Paolo Russo, Filippo Matarazzo, Giuseppe Mazzella, Maurizio Mazzeo, Massimo Memoli, Marzia Montalbano, Giuseppe Montalto, Alessandro Pieri, Nicola Passariello, Antonio Picciotto, Antonello Pietrangelo, Mario Pirisi, Tiziana Quirino, Giovanni Raimondo, Gian Ludovico Rapaccini, Giuliano Rizzardini, Mario Rizzetto, Maurizio Russello, Giuseppe Sabusco, Teresa Santantonio, Giorgio Soardo, Alessandri Amedea, Gabriella Verucchi, Francesco Vinelli, Anna Linda Zignego, Massimo Zuin, Antonio Ascione, Maria Vinci, Maria Graziella Pigozzi, Paolo Tundo, Giorgio Maria Saracco, Pietro Amoroso, Massimo Andreoni, Cosimo Colletta, Elke Erne, Angelo Salomone Megna, Alberto Biglino, Piergiorgio Chiriaco, Giuseppe Foti, Giancarlo Spinzi, Emilio D'amico, …], Foster G.R., Coppola C., Derbala M., Ferenci P., Orlandini A., Reddy K.R., Tallarico L., Shiffman M.L., Ahlers S., Bakalos G., Hassanein T., Basho J., Shabanaj G., Harxhi A., Debzi N., Afredj N., Guessab N., Mahindad N., Mahiou H., Aissaoui M., Al Qameesh J., Al Ghandoor Z., Assene C., Bastens B., Brixko C., Cool M., De Galocsy C., Delwaide J., George C., Laukens P., Lefebvre V., Mulkay J.-P., Nevens F., Servais B., Van Vlierberghe H., Horsmans Y., Henrion J., Sprengers D., Michielsen P., Bourgeois S., Lasser L., Langlet P., Robaeys G., Martinet J.-P., Warzee P., Hoste P., Reynaert H., Juriens I., Decaestecker J., Van Der Meersch F., Janssens F., Ahmetagic S., Verhaz A., Bevanda M., Calkic L., Ibrahimpasic N., Mesihovic R., Mello C.E., Ruiz F.J., Junior E.M., Ferraz M.L., Silva G., Mendes C., Lyra A., Silva M.H., Gomide G., Fernandes J.C., Pereira P., Correa M.C., Teixeira R., Yousry A., Hanno A., Gabr M., Omar A., Esmat G., Karatapanis S., Nikolopoulou V., Giannoulis G., Manolakopoulos S., Elefsiniotis I., Drakoulis C., Dimitroulopoulos D., Kanatakis S., Ketikoglou I., Mimidis K., Evgenidis N., Akriviades E., Vafiadi-Zoubouli I., Tsianos E., Mela M., Orfanou E., Mousoulis G., Karagiannis I., Manesis E., Varga M., Nemesanszky E., Fried K., Schuller J., Szalay F., Lengyel G., Tornai I., Banyai T., Lesch M., Nagy I., Gervain J., Tusnadi A., Schneider F., Szentgyorgyi L., Hunyady B., Vincze A., Tolvaj G., Varkonyi I., Makkai E., Enyedi J., Racz I., Hausinger P., Vaczi Z., Patai A., Ozsvar Z., Lakner L., Ribiczey P., Bhalla A., Somani S., Luaia R., Rao P., Philip M., Lawate P., Nagral A., Sood A., Parikh S., Merat S., Nassiri-Toosi M., Alavian S.-M., Zali M.R., Daryani N.E., Drenaggi D., Attili A.F., Bandiera F., Bassi P., Bellati G., Bellantani S., Brunetto M., Bruno S., Castelli F., Castellacci R., Cattelan A.M., Colombo M., Craxi A., D'angelo S., Colombo S., Demelia L., Di Perri G., Di Giacomo A., Ferrari C., Francisci D., Casinelli K., Ganga R., Costa C., Mangia A., Russo F.P., Matarazzo F., Mazzella G., Mazzeo M., Memoli M., Montalbano M., Montalto G., Pieri A., Passariello N., Picciotto A., Pietrangelo A., Pirisi M., Quirino T., Raimondo G., Rapaccini G.L., Rizzardini G., Rizzetto M., Russello M., Sabusco G., Santantonio T., Soardo G., Amedea A., Verucchi G., Vinelli F., Zignego A.L., Zuin M., Ascione A., Vinci M., Pigozzi M.G., Tundo P., Saracco G.M., Amoroso P., Andreoni M., Colletta C., Erne E., Megna A.S., Biglino A., Chiriaco P., Foti G., Spinzi G., D'amico E., Paik S.W., Ahn S.-H., Lee Y.N., Kim Y., Yang J., Han S.Y., Varghese R., Al Gharabally A., Askar H., Sharara A., Yaghi C., Abou Rached A., Houmani Z., Zaarour F., Dohaibi A., Ivanovski L., Joksimovic N., Abbas Z., Memon S., Mohsin A., Masood S., Hashmi Z., Halota W., Deron Z., Mazur W., Flisiak R., Lipczynski A., Musialik J., Piekarska A., Augustyniak K., Baka-Cwierz B., Simon K., Gietka A., Berak H., Sieklucki J., Radowska D., Szlauer B., Piekos T., Olszok I., Jablkowski M., Orszulak G., Warakomska I., Aleixo M.J., Valente C., Macedo G., Sarmento-Castro R., Roxo F., Faria T., Mansinho K., Velez J., Ramos J.P., Guerreiro H., Alberto S., Monteverde C., Serejo F., Peixe P., Malhado J., Curescu M., Streinu-Cercel A., Caruntu F., Livia H., Preotescu L., Arama V., Ancuta I., Gheorghe L., Stanciu C., Trifan A., Acalovschi M., Andreica V., Pascu O., Lencu M., Sporea I., Olteanu D., Ionita-Radu F., Fierbinteanu-Braticevici C., Motoc A., Silaghi R., Musat M., Coman F., Stan M., Cijevschi C., Miftode E., Delic D., Jesic R., Nozic D., Svorcan P., Fabri M., Konstantinovic L., Pelemis M., Jankovic G., Todorovic Z., Nagorni A., Kupcova V., Skladany L., Szantova M., Krkoska D., Jarcuska P., Schreter I., Oltman M., Bocakova J., Bunganic I., Holoman J., Giguere A., Abdou A.M.S., UCL - SSS/IREC-Institut de recherche expérimentale et clinique, UCL - SSS/IREC/GAEN-Pôle d'Hépato-gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie

Subjects
Genetics and Molecular Biology (all), Male, Chronic Hepatitis, Hepacivirus, Ribavirin/adverse effects, Asthenia/chemically induced, Polyethylene Glycol, Biochemistry, Polyethylene Glycols, Body Mass Index, Chronic Liver Disease, 0302 clinical medicine, Neutropenia/chemically induced, Interferon-alpha/adverse effects, Medicine, Chronic, lcsh:Science, Liver Diseases, virus diseases, Antiviral Agents/adverse effects, Cohort, Science & Technology - Other Topics, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Cohort study, Human, medicine.medical_specialty, Alpha interferon, Gastroenterology and Hepatology, Antiviral Agents, Microbiology, Dose-Response Relationship, 03 medical and health sciences, Pharmacotherapy, Hepatitis C, Chronic/drug therapy, Dose Prediction Methods, Drug Therapy, Anemia/chemically induced, Humans, Hemoglobin, Aged, Medicine and health sciences, Biochemistry, Genetics and Molecular Biology (all), Hepaciviru, Science & Technology, Dose-Response Relationship, Drug, Flaviviruses, lcsh:R, Organisms, Biology and Life Sciences, Proteins, medicine.disease, digestive system diseases, chemistry, Agricultural and Biological Sciences (all), Withholding Treatment, Asthenia, Immunology, Proportional Hazards Model, lcsh:Q, Human medicine, RNA viruses, Physiology, lcsh:Medicine, Peginterferon-alfa, Polyethylene Glycols/adverse effects, Adult, Anemia, Cohort Studies, Female, Hepatitis C, Chronic, Host-Pathogen Interactions, Interferon-alpha, Middle Aged, Neutropenia, Outcome Assessment (Health Care), Proportional Hazards Models, RNA, Viral, Recombinant Proteins, Ribavirin, Medicine (all), chemistry.chemical_compound, Outcome Assessment, Health Care, Medicine and Health Sciences, 030212 general & internal medicine, Viral, Pathology and laboratory medicine, Multidisciplinary, biology, Hepatitis C virus, Pharmaceutics, Hepatitis C, Hematology, Recombinant Protein, Outcome Assessment (Health Care)/methods, Medical microbiology, Host-Pathogen Interaction, Multidisciplinary Sciences, Physiological Parameters, Research Design, Combination, Viruses, Drug, Pathogens, Host-Pathogen Interactions/drug effects, Research Article, Clinical Research Design, Research and Analysis Methods, Internal medicine, Recombinant Proteins/adverse effects, RNA, Viral/blood, Antiviral Agent, business.industry, Body Weight, Hepacivirus/drug effects, Viral pathogens, biology.organism_classification, Hepatitis viruses, Microbial pathogens, RNA, Adverse Events, Cohort Studie, business
Abstract

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA

Published
2015

47. Different adjuvants induce common innate pathways that are associated with enhanced adaptive responses against a model antigen in humans

Author

Burny, Wivine, Callegaro, Andrea, Bechtold, Viviane, Clément, Frédéric, Delhaye, Sophie, Fissette, Laurence, Janssens, Michel, Leroux-Roels, Geert, Marchant, Arnaud, van den Berg, Robert R.A., Garçon, Nathalie, van der Most, Robbert, Didierlaurent, Arnaud M, Carletti, Isabelle, Esen, Meral, Gabor, Julian Justin, Haelterman, Edwige, Hervé, Caroline, Horsmans, Y., Kremsner, Peter Gottfried Gottfried P.G., Moris, Philippe, Schwarz, Tino F, da Silva, Fernanda Tavares, Van Belle, Pascale, Van Damme, Pierre, Zuchner, Dirk, Burny, Wivine, Callegaro, Andrea, Bechtold, Viviane, Clément, Frédéric, Delhaye, Sophie, Fissette, Laurence, Janssens, Michel, Leroux-Roels, Geert, Marchant, Arnaud, van den Berg, Robert R.A., Garçon, Nathalie, van der Most, Robbert, Didierlaurent, Arnaud M, Carletti, Isabelle, Esen, Meral, Gabor, Julian Justin, Haelterman, Edwige, Hervé, Caroline, Horsmans, Y., Kremsner, Peter Gottfried Gottfried P.G., Moris, Philippe, Schwarz, Tino F, da Silva, Fernanda Tavares, Van Belle, Pascale, Van Damme, Pierre, and Zuchner, Dirk

Abstract

To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B ,AS01E ,AS03, AS04, or Alum/ Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B ,AS01E ,and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

48. Pharmacokinetic interactions between simeprevir and ledipasvir in treatment-naive hepatitis C virus genotype 1-infected patients without cirrhosis treated with a simeprevir-sofosbuvir-ledipasvir regimen

Author

Bourgeois, Stefan, Hillewaert, Vera, Van Remoortere, Pieter, Van De Logt, Jolanda, Ouwerkerk-Mahadevan, Sivi, Horsmans, Y., Nevens, Frederik, Van Vlierberghe, Hans, Moreno, Christophe, Beumont, Maria, Vijgen, Leen, Van Eygen, Veerle, Luo, Donghan, Bourgeois, Stefan, Hillewaert, Vera, Van Remoortere, Pieter, Van De Logt, Jolanda, Ouwerkerk-Mahadevan, Sivi, Horsmans, Y., Nevens, Frederik, Van Vlierberghe, Hans, Moreno, Christophe, Beumont, Maria, Vijgen, Leen, Van Eygen, Veerle, and Luo, Donghan

Abstract

Interactions between simeprevir (hepatitis C virus [HCV] NS3/4A protease inhibitor) and ledipasvir (HCV NS5A replication complex inhibitor) were investigated in treatment-naive HCV genotype 1-infected patients without cirrhosis, treated with simeprevir-sofosbuvir-ledipasvir in a two-panel, phase 2, open-label study. Patients had stable background treatment with sofosbuvir (400 mg once daily [QD]). In panel 1 (n 20), the effect of ledipasvir (90 mg QD) on simeprevir (150 mg QD) was studied. Patients received simeprevir and sofosbuvir from days 1 to 14; steady-state pharmacokinetics (PK) of simeprevir was assessed (day 14). On day 15, ledipasvir was added and steady-state PK of simeprevir in the combination was evaluated (day 28). In panel 2 (n 20), the effect of simeprevir on ledipasvir was investigated. From days 1 to 14, patients received ledipasvir and sofosbuvir and steady-state PK of ledipasvir was assessed (day 14). On day 15, simeprevir was added and a full PK profile was obtained (day 28). The least-squares mean maximum plasma concentration and area under the concentration-time curve (90% confidence interval) increased 2.3-fold (2.0- to 2.8-fold) and 3.1-fold (2.4- to 3.8-fold) for simeprevir, respectively (panel 1), and 1.6-fold (1.4- to 1.9-fold) and 1.7-fold (1.6- to 2.0-fold) for ledipasvir, respectively (panel 2), in the presence versus the absence of the other drug. All patients achieved sustained virologic responses 12 weeks after treatment end. Adverse events, mainly grade 1/2, occurred in 80% of patients; the most common was photosensitivity (45%). Due to the magnitude of interaction and the limited amount of safety data available, the use of this treatment combination is not recommended. (This study has been registered at ClinicalTrials.gov under registration no. NCT02421211.), SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

49. Efficacy, safety and pharmacokinetics of simeprevir and TMC647055/ritonavir with or without ribavirin and JNJ-56914845 in HCV genotype 1 infection

Author

Bourgeois, Stefan, Francque, Sven, Vijgen, Leen, Kakuda, Thomas T.N., Hoeben, Eva, Luo, Donghan, Vandebosch, An, Jacquemyn, Bert, Van Remoortere, Pieter, Verloes, René, Van Vlierberghe, Hans, Moreno, Christophe, Orlent, Hans, Nevens, Frederik, Arasteh, Keikawus, Horsmans, Y., Schattenberg, Jörn Markus, Buggisch, Peter, Bourgeois, Stefan, Francque, Sven, Vijgen, Leen, Kakuda, Thomas T.N., Hoeben, Eva, Luo, Donghan, Vandebosch, An, Jacquemyn, Bert, Van Remoortere, Pieter, Verloes, René, Van Vlierberghe, Hans, Moreno, Christophe, Orlent, Hans, Nevens, Frederik, Arasteh, Keikawus, Horsmans, Y., Schattenberg, Jörn Markus, and Buggisch, Peter

Abstract

Background: A Phase 2a, open-label study (NCT01724086) was conducted to assess the efficacy and safety of a once-daily, 2-direct-acting-antiviral-agent (2-DAA) combination of simeprevir + TMC647055/ritonavir ± ribavirin and of the 3-DAA combination of simeprevir + TMC647055/ritonavir + JNJ-56914845 in chronic hepatitis C virus genotype (GT)1-infected treatment-naïve and prior-relapse patients. Methods: The study comprised four 12-week treatment panels: Panel 1 (n = 10; GT1a) and Panel 2-Arm 1 (n = 12; GT1b): simeprevir 75 mg once daily + TMC647055 450 mg once daily/ritonavir 30 mg once daily + ribavirin 1000-1200 mg/day; Panel 2-Arm 2 (n = 9; GT1b): simeprevir 75 mg + TMC647055 450 mg/ritonavir 30 mg without ribavirin; Panel 3: simeprevir 75 mg + TMC647055 600 mg/ritonavir 50 mg with (Arm 1: GT1a; n = 7) or without (Arm 2: GT1b; n = 8) ribavirin; Panel 4: simeprevir 75 mg + TMC647055 450 mg/ritonavir 30 mg + JNJ-56914845 30 mg once daily (Arm 1: n = 22; GT1a/GT1b) or 60 mg once daily (Arm 2: n = 22; GT1a/GT1b). Primary endpoint was sustained virologic response 12 weeks after end of treatment (12 weeks of combination treatment; SVR12). Results: In Panel 1 and Panel 2-Arm 1, 5/10 and 6/12 (50%) GT1a/GT1b + ribavirin patients achieved SVR12, versus 3/9 (33%) GT1b without ribavirin patients in Panel 2-Arm 2. In Panel 3-Arm 1 and Panel 3-Arm 2, 6/7 (86%) GT1a + ribavirin and 4/8 (50%) GT1b without ribavirin patients, respectively, achieved SVR12. In Panel 4, 10/14 (71%) and 14/15 (93%) GT1a patients in Arms 1 and 2 achieved SVR12 compared with 8/8 and 7/7 (100%) GT1b patients in each arm, respectively. No deaths, serious adverse events (AEs), Grade 4 AEs or AEs leading to treatment discontinuation occurred. Conclusions: The 2- and 3-DAA combinations were well tolerated. High SVR rates of 93% and 100% in GT1a- and GT1b-infected patients, respectively, were achieved in this study by combining simeprevir with JNJ-56914845 60 mg and TMC647055/ritonavir. Trial registration:NC, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

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