Abstract LBPS9/5
 
Simeprevir (TMC435) plus Peginterferon/Ribavirin in Patients Co-infected with HCV genotype-1 and HIV-1: Primary Analysis of the C212 Study Print
 
D. Dieterich1, J. Rockstroh2, C. Orkin3, F. Gutiérrez4, M.B. Klein5, J. Reynes6, W. Jessner7, A. Jenkins8, O. Lenz7, S. Ouwerkerk-Mahadevan7, M. Peeters7, G. De La Rosa9, L. Tambuyzer7, M. Beumont-Mauviel7
1Icahn School of Medicine at Mount Sinai, New York, United States, 2Mediz. Universitätsklinik-Immunologische Ambulanz, Bonn, Germany, 3Royal London Hospital, London, United Kingdom, 4Hospital General de Elche and Universidad Miguel Hernández, Alicante, Spain, 5McGill University Health Centre, Montreal, Canada, 6Hopital Gui De Chauliac, Montpellier, France, 7Janssen Infectious Diseases BVBA, Beerse, Belgium, 8Janssen Research & Development, Raritan, United States, 9Janssen Global Services, Titusville, United States
 
Objectives: HIV co-infection accelerates progression of HCV-associated liver disease. Simeprevir is a potent, oral, HCV NS3/4A protease inhibitor in late-stage development for the treatment of chronic HCV infection. Given once-daily (QD) as a single pill, simeprevir is active against HCV genotypes 1, 2, 4, 5 and 6, with a favourable safety profile. This Phase III, open-label trial evaluated the safety and efficacy of simeprevir (versus historic controls) in patients co-infected with HCV genotype-1 and HIV-1.
Methods: Patients received simeprevir (150 mg QD) with peginterferon and ribavirin (PR) for 12 weeks. Treatment-naïve patients and prior relapsers (without cirrhosis) received response-guided therapy (RGT) with PR up to 24 or 48 weeks. All other patients (prior null responders, -partial responders and all patients with cirrhosis) received PR up to 48 weeks. The primary endpoint was the sustained virologic response (SVR) rate 12 weeks after end of treatment (EOT).
Results: 106 patients were enrolled and treated, 93 were receiving HAART. SVR12 rates were 79.2% in HCV treatment-naive patients, 57.1% in prior null responders (both p< 0.001 versus historic controls; ITT), 86.7% in -relapsers and 70.0% in -partial responders (Table 1). Most eligible patients (88.5%; 54/61) met RGT criteria, 87% (47/54) of whom achieved SVR12. SVR12 rates were high irrespective of baseline Metavir fibrosis score: 80.0% and 63.6% overall for patients with of F0-F2 and F3-F4 respectively although sub-groups were small (Table 1). Up to Week 12, the most common adverse events (AEs) were consistent with peginterferon-based therapy (fatigue, headache, nausea, neutropenia). Most AEs were grade 1 or 2. Serious AEs occurred in 5.7% of patients, none were fatal.
Conclusion: Simeprevir was generally well tolerated with safety similar to studies in patients without HIV and high SVR12 rates in HCV treatment-naïve patients, prior null-responders, -partial responders and -relapsers co-infected with HIV-1.
Endpoints, % (n)OverallHCV treatment naiveHCV treatment experienced (n=53)
   Prior relapsersPrior partial respondersPrior null responders
SVR1273.6
(78/106)
79.2
(42/53)*
86.7
(13/15)
70.0
(7/10)
57.1
(16/28)*
SVR12 by Metavir score:     
F0-F280.0
(36/45)
88.9
(24/27)
77.8
(7/9)
50.0
(1/2)
57.1
(4/7)
F3-F463.6
(14/22)
57.1
(4/7)
100.0
(2/2)
66.7
(2/3)
60.0
(6/10)
On-treatment failure27.4
(29/106)
9.4
(5/53)
0
(0/15)
20
(2/10)
39.3
(11/28)
HCV viral relapse†10.3
(9/87)
10.4
(5/48)
13.3
(2/15)
0
(0/7)
11.8
(2/17)
*p<0.001 vs historical PR-only controls (SVR12 for PR controls was assumed to be 29.0% in treatment naive patients and 5.4% in prior null responders); †Calculated only for patients with undetectable HCV RNA (or unconfirmed detectable) at EOT and with at least one follow-up HCV RNA measurement

ITT, intent-to-treat (population includes all patients who were enrolled and received at least one dose of study medication); On-treatment failure defined as confirmed detectable HCV RNA at EOT; HCV viral relapse defined as failure but with undetectable (or unconfirmed detectable) HCV RNA at EOT

Metavir scores as follows: F0, no fibrosis; F1, portal fibrosis without septa; F2, portal fibrosis with few septa; F3, numerous septa without cirrhosis; F4, cirrhosis

EOT, end of treatment; n, number; SVR, sustained virologic response
[Table 1]


Assigned speakers:
MD Douglas Dieterich , Icahn School of Medicine at Mount Sinai , New York , United States

Assigned in sessions:
18.10.2013, 14:00-16:00, Parallel Session, PS9, HIV and Hepatitis Co-Infection, Bozar (Plenary Hall)