Gastroenterology

Gastroenterology

Volume 146, Issue 7, June 2014, Pages 1669-1679.e3
Gastroenterology

Original Research
Full Report: Clinical—Liver
Simeprevir With Peginterferon and Ribavirin Leads to High Rates of SVR in Patients With HCV Genotype 1 Who Relapsed After Previous Therapy: A Phase 3 Trial

https://doi.org/10.1053/j.gastro.2014.02.051Get rights and content
Under a Creative Commons license
open access

Background & Aims

Simeprevir is an oral, once-daily inhibitor of hepatitis c virus (HCV) protease NS3/4A. We investigated the safety and efficacy of simeprevir with peg-interferon α-2a and ribavirin (PR) in a randomized, double-blind, placebo-controlled, phase 3 trial of patients with HCV genotype 1 infection who relapsed after previous interferon-based therapy.

Methods

Patients were assigned randomly (2:1) to groups given simeprevir (150 mg, once daily) and PR (n = 260) or placebo and PR (n = 133) for 12 weeks. Patients then were given PR alone for 12 or 36 weeks (simeprevir group, based on response-guided therapy criteria) or 36 weeks (placebo group).

Results

Simeprevir and PR was significantly superior to placebo and PR; rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were 79.2% vs 36.1%, respectively (43.8% difference; 95% confidence interval, 34.6–53.0; P < .001). Among patients given simeprevir, 92.7% met the response-guided therapy criteria and were eligible to complete PR at week 24; of these, 83.0% achieved SVR12. HCV RNA was undetectable at week 4 in 77.2% of patients given simeprevir and 3.1% given placebo. On-treatment failure and relapse rates were lower among patients given simeprevir and PR than those given placebo and PR (3.1% vs 27.1%, and 18.5% vs 48.4%, respectively). Patients given simeprevir did not have adverse events beyond those that occurred in patients given PR alone. Most adverse events were grades 1/2; the prevalence of anemia and rash was similar in both groups. Patients in both groups reported similar severity of fatigue and functional impairments during the study, but duration was reduced among patients given simeprevir.

Conclusions

In a phase 3 trial of patients who had relapsed after interferon-based therapy, the addition of simeprevir to PR was generally well tolerated, with an SVR12 rate of 79.2%. Most patients (92.7%) receiving simeprevir were able to shorten therapy to 24 weeks. ClinicalTrials.gov number: NCT01281839.

Keywords

PROMISE
Chronic Hepatitis C
Drug
DAA

Abbreviations used in this paper

AE
adverse event
CI
confidence interval
DAA
direct-acting antiviral agent
EC50
median effective concentration
EOT
end of treatment
FDA
Food and Drug Administration
HCV
hepatitis C virus
IQR
interquartile range
PegIFN
peginterferon
PR
peginterferon α-2a/ribavirin
RBV
ribavirin
RGT
response-guided treatment
RVR
rapid virologic response
SAE
serious adverse event
SVR
sustained virologic response
SVR12
sustained virologic response at 12 weeks
SVR24
sustained virologic response at 24 weeks

Cited by (0)

Conflicts of interest These authors disclose the following: Xavier Forns has received unrestricted grant support from Jansen and Merck Sharp and Dohme Ltd (MSD), and has acted as an advisor for Jansen, Gilead, MSD, and Abbott. Eric Lawitz has received research/grant support from AbbVie, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb (BMS), Gilead Sciences, GlaxoSmithKline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Medtronic, Merck & Co, Novartis, Presidio, Roche, Santaris Pharmaceuticals, and Vertex Pharmaceuticals; has acted as a speaker for Gilead, Kadmon, Merck, and Vertex; and has participated in Advisory Boards for AbbVie, Achillion Pharmaceuticals, BioCryst, Biotica, Enanta, Idenix Pharmaceuticals, Janssen, Merck & Co, Novartis, Santaris Pharmaceuticals, Theravance, and Vertex Pharmaceuticals. Stefan Zeuzem has acted as a consultant for Abbvie, Achillion, BMS, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Novartis, Presidio, Roche, Santaris, and Vertex. Ed Gane has acted as an advisor for Janssen, Gilead, AbbVie, Novartis, Tibotec, Achillion, and Roche; and as a speaker for Gilead, Roche, and Novartis. Jean Pierre Bronowicki has been a clinical investigator, speaker, and/or consultant for Boehringer Ingelheim, BMS, Gilead Sciences, Janssen Pharmaceuticals, MSD, Novartis, and Roche. Pietro Andreone has received research grants from Gilead, MSD, and Roche, and has acted as an advisor for Janssen, MSD, and Roche; and as a consultant for BMS and MSD. Ashley Brown has acted as an advisor and/or speaker for Abbvie, Achillion, BMS, Boehringer Ingelheim, Gilead, Janssen, Merck, Novartis, Presidio, and Roche. Monika Peeters, Oliver Lenz, Rekha Sinha, and Maria Beumont–Mauviel are employees of Janssen Infectious Diseases. Sivi Ouwerkerk–Mahadevan is an employee of Janssen Research & Development. Jane Scott, Guy De La Rosa, and Ronald Kalmeijer are employees of Janssen Global Services, LLC. Andrzej Horban discloses no conflicts.

Funding Supported by Janssen.