telaprevir in treatment naïve gt-1 advance (study 108)

Hepatitisweb study

Hepatitisweb study

Telaprevir in Treatment Naïve GT-1ADVANCE (Study 108)

Phase 3

Treatment Naïve

Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.

Hepatitisweb studySource: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE: Study Design

Drug DosingTelaprevir = 750 mg every 8 hoursPeginterferon alfa-2a = 180 µg weeklyRibavirin = 1000 mg/day for wt < 75 kg; 1200 mg/day for wt > 75 kg

ADVANCE: Study Features N = 1,088 enrolled Randomized, double-blind, placebo-controlled, Phase 3 trial Genotype 1 HCV and treatment naïve 77% with HCV RNA ≥ 800,000 IU/ml Randomized to one of 3 arms RVR = HCV RNA undetectable at week 4 eRVR = HCV RNA undetectable at weeks 4 & 12 Erythroid stimulating agents not allowed Telaprevir-treated patients without eRVR received PR up to week 48

Hepatitisweb study

Telaprevir+

PEG + RBV

eRVR: PEG + RBV

No eRVR: PEG + RBV

Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Treatment Regimens

8 24 48Week 0

Telaprevir+

PEG + RBV

Placebo+

PEG + RBVPEG + RBV

12

T8PR 24 or 48

T12PR 24 or 48

PR48

N =364

N =363

N =361

PEG +

RBV

eRVR: PEG + RBV

No eRVR: PEG + RBV

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results

ADVANCE: SVR24 by Regimen


T8/PR24 or 48 T12/PR24 or 48 PR 480

20

40

60

80

100

6975

44

Patie

nts

with

SVR

(%)

SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin

250/364 271/363 158/361

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: RVR and eRVR Rates

ADVANCE: Patients with RVR and eRVR


RVR (week 4) eRVR (week 12)0

20

40

60

80

100

6657

68

58

9 8

T8/PR24 or 48T12/PR24 or 48PR48

Patie

nts

(%)

T = Telaprevir; PR = Peginterferon + Ribavirin; RVR = rapid virologic response; eRVR = extended rapid virologic response

242/364 246/363 34/361 207/364 212/363 29/361

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results According to eRVR

ADVANCE: SVR24 by eRVR Status


With eRVR Without eRVR0

20

40

60

80

100

83

50

89

54

97

39

T8/PR24 or 48T12/PR24 or 48PR48

Patie

nts

with

SVR

(%)

T = Telaprevir; PR= Peginterferon + Ribavirin; SVR = Sustained Virologic ResponseeRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)

171/207 189/212 28/29 79/157 82/151 130/342

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results According to eRVR

ADVANCE: SVR24 by eRVR Status


T8/PR24 or 48 T12/PR24 or 48 PR 480

20

40

60

80

100

8389

97

50 54

39

With eRVR Without eRVR

Patie

nts

with

SVR

(%)

SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin; eRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)

171/207 189/212 28/2979/157 82/151 130/342

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results According to Race

ADVANCE: SVR24 by Race


White Black Hispanic0

20

40

60

80

100

70

5866

75

62

74

46

25

39

T8/PR 24 or 48 T12/PR24 or 48 PR48

Patie

nts

with

SVR

(%)


221/315 147/318 16/26244/325 7/28 26/35 15/3829/4423/40

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results by Baseline HCV RNA

ADVANCE: SVR24 by Baseline HCV RNA Level


< 800,000 IU/ml ≥800,000 IU/ml 0

20

40

60

80

100

79

66

78 7470

36

T8/PR 24 or 48 T12/PR24 or 48 PR48

Baseline HCV RNA Level

Patie

nts

with

SVR

(%)


184/279 207/28164/82 57/8267/85 101/279

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results by Fibrosis Stage

ADVANCE: SVR24 by Fibrosis Stage

Source: Jacobson IM, et. al. Hepatology. 2010;52 (Supplement 1):427A. Abstract 211.

No or Minimal Fi-brosis

Portal Fibrosis Bridging Fibrosis Cirrhosis0

20

40

60

80

100

79

69

58

42

8175

62 62

46 48

33 33

T8/PR24 or 48 T12/PR24 or 48 PR48

Patie

nts

with

SVR

(%)


101/128 109/134 67/147 104/151 117/156 67/141 17/52 7/2132/52 13/2134/59 11/26

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Adverse EffectsADVANCE: Percentage of Patients with Anemia


Hb < 10 g/dL Hb < 8.5 g/dL0

10

20

30

40

50

60

40

9

36

914

2

T8/PR24 or 48T12/PR24 or 48PR48

Hemoglobin (Hb) Nadir Through Week 12

Patie

nts

(%)

T = Telaprevir; PR = Peginterferon + Ribavirin

146/364 33/364 33/363131/363 7/36151/361

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Adverse EffectsADVANCE: Percentage of Patients with Rash


Rash Severe (Grade 3) Rash0

10

20

30

40

50

60

35

4

37

6

24

1

T8/PR24 or 48T12/PR24 or 48PR48

Patie

nts

(%)

T = Telaprevir; PR = Peginterferon + Ribavirin

15/36422/363

4/361129/364 133/363 88/361

Hepatitisweb study

Telaprevir for Treatment-Naïve HCV Genotype 1SVR Rates by IL28B rs12979860 Genotype

ADVANCE: SVR24 by rs12979860 Genotype

Source: Telaprevir (Incivek) Prescribing Information. Vertex Pharmaceuticals.

PR48 T12/PR24 or 480

20

40

60

80

100

23

73

25

7164

90

T/T C/T C/C

Treatment Regimen

Patie

nts

with

SVR

(%)

PR48 = Peginteron/Ribavirin x 48 weeks PR/T12 = Peginteron/Ribavirin + Telaprevir x 12 weeks

45/5035/556/26 16/2220/80 48/68

Hepatitisweb studySource: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.

Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Conclusions

Conclusions: “Telaprevir with peginterferon–ribavirin, as compared with peginterferon–ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients.”

telaprevir in treatment naïve gt-1 advance (study 108)

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