Tags

Type your tag names separated by a space and hit enter

Simeprevir versus telaprevir with peginterferon and ribavirin in previous null or partial responders with chronic hepatitis C virus genotype 1 infection (ATTAIN): a randomised, double-blind, non-inferiority phase 3 trial.
Lancet Infect Dis. 2015 Jan; 15(1):27-35.LI

Abstract

BACKGROUND

We did a phase 3 study in previous non-responders with chronic hepatitis C virus (HCV) genotype 1 infection and compensated liver disease that related to the standard of care for these patients at the time this study was initiated. We investigated whether simeprevir is non-inferior in terms of efficacy to telaprevir, each in combination with peginterferon alfa-2a and ribavirin.

METHODS

We did this randomised, double-blind, phase 3 trial at 169 investigational sites in 24 countries. We enrolled adults (≥18 years) with chronic HCV genotype 1 infection, compensated liver disease, and plasma HCV RNA higher than 10 000 IU/mL who were null or partial responders during at least one previous course of peginterferon alfa-2a and ribavirin treatment. We randomly assigned (1:1) patients (stratified by HCV genotype 1 subtype [1a plus other/1b] and previous treatment response [partial or null]) to receive simeprevir (150 mg once a day) plus telaprevir placebo (three times a day 7-9 h apart) or telaprevir (750 mg three times a day) plus simeprevir placebo (once a day) in combination with peginterferon alfa-2a and ribavirin for 12 weeks followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. The primary efficacy endpoint was sustained virological response 12 weeks after end of treatment (SVR12) in the intention-to-treat and the per-protocol population. We compared groups with the Cochran-Mantel-Haenszel test. We established a non-inferiority margin of 12%. Adverse events were reported descriptively. This trial is registered with ClinicalTrials.gov, number NCT01485991.

FINDINGS

Patient screening began on Jan 19, 2012, and the last visit was on April 7, 2014. We included 763 patients (472 previous null responders [62%]). Simeprevir and peginterferon alfa-2a and ribavirin was non-inferior to telaprevir and peginterferon alfa-2a and ribavirin for SVR12 (54% [203/379] vs 55% [210/384]; difference -1·1%, 95% CI -7·8 to 5·5; p=0·0007). SVR12 was achieved in 70% (101/145) versus 68% (100/146) of previous partial responders and 44% (102/234) versus 46% (110/238) of previous null responders with simeprevir and peginterferon alfa-2a and ribavirin and telaprevir and peginterferon alfa-2a and ribavirin treatment, respectively. We recorded differences between treatment groups in simeprevir or telaprevir-related adverse events (69% [261/379] in the simeprevir group vs 86% [330/384] in the telaprevir group), serious adverse events (2% [8/379] vs 9% [33/384]), and adverse events leading to simeprevir or telaprevir discontinuation (2% [7/379] vs 8% [32/384]).

INTERPRETATION

Simeprevir once a day with peginterferon alfa-2a and ribavirin was well tolerated in HCV genotype 1-infected previous non-responders and was non-inferior to telaprevir, thus providing an alternative treatment in areas of the world where all-oral HCV regimens are not available or accessible.

FUNDING

Janssen.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: rajender.reddy@uphs.upenn.edu.Department of Medicine, JW Goethe University Hospital, Frankfurt, Germany.Hospices Civils de Lyon, INSERM U1052, Lyon 1 University, Lyon, France.Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.Warsaw Medical University and Hospital of Infectious Diseases, Warsaw, Poland.Gastromedica Clinic, University Hospital St Spiridon, Iasi, Romania.CIPREC, Buenos Aires, Argentina.Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna and AOU Policlinico Sant'Orsola-Malpighi, Bologna, Italy.Storr Liver Unit, Westmead Hospital and Westmead Millennium Institute, Westmead, NSW, Australia.Janssen Infectious Diseases BVBA, Beerse, Belgium.Janssen Research and Development, Spring House, PA, USA.Janssen Research and Development, Titusville, NJ, USA.Janssen Infectious Diseases BVBA, Beerse, Belgium.Janssen Research and Development, Beerse, Belgium.Janssen Infectious Diseases BVBA, Beerse, Belgium.Janssen Global Services, High Wycombe, UK.Janssen Infectious Diseases BVBA, Beerse, Belgium.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25482330

Citation

Reddy, K Rajender, et al. "Simeprevir Versus Telaprevir With Peginterferon and Ribavirin in Previous Null or Partial Responders With Chronic Hepatitis C Virus Genotype 1 Infection (ATTAIN): a Randomised, Double-blind, Non-inferiority Phase 3 Trial." The Lancet. Infectious Diseases, vol. 15, no. 1, 2015, pp. 27-35.
Reddy KR, Zeuzem S, Zoulim F, et al. Simeprevir versus telaprevir with peginterferon and ribavirin in previous null or partial responders with chronic hepatitis C virus genotype 1 infection (ATTAIN): a randomised, double-blind, non-inferiority phase 3 trial. Lancet Infect Dis. 2015;15(1):27-35.
Reddy, K. R., Zeuzem, S., Zoulim, F., Weiland, O., Horban, A., Stanciu, C., Villamil, F. G., Andreone, P., George, J., Dammers, E., Fu, M., Kurland, D., Lenz, O., Ouwerkerk-Mahadevan, S., Verbinnen, T., Scott, J., & Jessner, W. (2015). Simeprevir versus telaprevir with peginterferon and ribavirin in previous null or partial responders with chronic hepatitis C virus genotype 1 infection (ATTAIN): a randomised, double-blind, non-inferiority phase 3 trial. The Lancet. Infectious Diseases, 15(1), 27-35. https://doi.org/10.1016/S1473-3099(14)71002-3
Reddy KR, et al. Simeprevir Versus Telaprevir With Peginterferon and Ribavirin in Previous Null or Partial Responders With Chronic Hepatitis C Virus Genotype 1 Infection (ATTAIN): a Randomised, Double-blind, Non-inferiority Phase 3 Trial. Lancet Infect Dis. 2015;15(1):27-35. PubMed PMID: 25482330.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simeprevir versus telaprevir with peginterferon and ribavirin in previous null or partial responders with chronic hepatitis C virus genotype 1 infection (ATTAIN): a randomised, double-blind, non-inferiority phase 3 trial. AU - Reddy,K Rajender, AU - Zeuzem,Stefan, AU - Zoulim,Fabien, AU - Weiland,Ola, AU - Horban,Andrzej, AU - Stanciu,Carol, AU - Villamil,Federico Guillermo, AU - Andreone,Pietro, AU - George,Jacob, AU - Dammers,Elisabeth, AU - Fu,Min, AU - Kurland,Darryl, AU - Lenz,Oliver, AU - Ouwerkerk-Mahadevan,Sivi, AU - Verbinnen,Thierry, AU - Scott,Jane, AU - Jessner,Wolfgang, Y1 - 2014/12/05/ PY - 2014/12/9/entrez PY - 2014/12/9/pubmed PY - 2015/3/10/medline SP - 27 EP - 35 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 15 IS - 1 N2 - BACKGROUND: We did a phase 3 study in previous non-responders with chronic hepatitis C virus (HCV) genotype 1 infection and compensated liver disease that related to the standard of care for these patients at the time this study was initiated. We investigated whether simeprevir is non-inferior in terms of efficacy to telaprevir, each in combination with peginterferon alfa-2a and ribavirin. METHODS: We did this randomised, double-blind, phase 3 trial at 169 investigational sites in 24 countries. We enrolled adults (≥18 years) with chronic HCV genotype 1 infection, compensated liver disease, and plasma HCV RNA higher than 10 000 IU/mL who were null or partial responders during at least one previous course of peginterferon alfa-2a and ribavirin treatment. We randomly assigned (1:1) patients (stratified by HCV genotype 1 subtype [1a plus other/1b] and previous treatment response [partial or null]) to receive simeprevir (150 mg once a day) plus telaprevir placebo (three times a day 7-9 h apart) or telaprevir (750 mg three times a day) plus simeprevir placebo (once a day) in combination with peginterferon alfa-2a and ribavirin for 12 weeks followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. The primary efficacy endpoint was sustained virological response 12 weeks after end of treatment (SVR12) in the intention-to-treat and the per-protocol population. We compared groups with the Cochran-Mantel-Haenszel test. We established a non-inferiority margin of 12%. Adverse events were reported descriptively. This trial is registered with ClinicalTrials.gov, number NCT01485991. FINDINGS: Patient screening began on Jan 19, 2012, and the last visit was on April 7, 2014. We included 763 patients (472 previous null responders [62%]). Simeprevir and peginterferon alfa-2a and ribavirin was non-inferior to telaprevir and peginterferon alfa-2a and ribavirin for SVR12 (54% [203/379] vs 55% [210/384]; difference -1·1%, 95% CI -7·8 to 5·5; p=0·0007). SVR12 was achieved in 70% (101/145) versus 68% (100/146) of previous partial responders and 44% (102/234) versus 46% (110/238) of previous null responders with simeprevir and peginterferon alfa-2a and ribavirin and telaprevir and peginterferon alfa-2a and ribavirin treatment, respectively. We recorded differences between treatment groups in simeprevir or telaprevir-related adverse events (69% [261/379] in the simeprevir group vs 86% [330/384] in the telaprevir group), serious adverse events (2% [8/379] vs 9% [33/384]), and adverse events leading to simeprevir or telaprevir discontinuation (2% [7/379] vs 8% [32/384]). INTERPRETATION: Simeprevir once a day with peginterferon alfa-2a and ribavirin was well tolerated in HCV genotype 1-infected previous non-responders and was non-inferior to telaprevir, thus providing an alternative treatment in areas of the world where all-oral HCV regimens are not available or accessible. FUNDING: Janssen. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/25482330/Simeprevir_versus_telaprevir_with_peginterferon_and_ribavirin_in_previous_null_or_partial_responders_with_chronic_hepatitis_C_virus_genotype_1_infection__ATTAIN_:_a_randomised_double_blind_non_inferiority_phase_3_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(14)71002-3 DB - PRIME DP - Unbound Medicine ER -