Study Design |
HCV Status |
Treatment |
Results |
Phase Ib, randomized, dose-escalation, double-blind, placebo-controlled (n=34)22
|
Genotype 1, treatment-naïve (21%) and experienced (79%) |
Telaprevir 450 mg q8h, 750 mg q8h, or 1250 mg q12h, or placebo x 14 days |
Change in HCV RNA level on day 14: Placebo: no change Telaprevir 450 mg q8h: –3.46 log10 IU/ml Telaprevir 750 mg q8h: –4.77 log10 IU/ml Telaprevir 1250 mg q12h: –3.49 log10 IU/ml |
Phase I, randomized (n=20)25
|
Genotype 1, treatment-naïve |
Placebo + peginterferon alfa-2a, telaprevir alone, or telaprevir + peginterferon alfa-2a x 14 days Dosing: telaprevir 1250 mg x 1, then 750 mg q8h; peginterferon alfa-2a 180 μg/wk |
Change in HCV RNA level on day 15: Placebo + peginterferon alfa-2a: –1.09 log10 IU/ml Telaprevir alone: –3.99 log10 IU/ml Telaprevir + peginterferon alfa-2a: –5.49 log10 IU/ml |
Phase II, single-arm, open-label (n=12)26
|
Genotype 1, treatment-naïve |
Telaprevir + peginterferon alfa-2a + ribavirin x 28 days, then optional 44 wks of peginterferon alfa-2a + ribavirin Dosing: telaprevir 1250 mg x 1, then 750 mg q8h; peginterferon alfa-2a 180 μg/wk; ribavirin 1000 or 1200 mg/day |
Change in HCV RNA level on day 28: Decrease of ≥ 4 log10 IU/ml in all 12 patients |
Phase IIb, randomized, double-blind, placebo-controlled, multicenter (PROVE1) (n=263)27
|
Genotype 1, treatment-naïve |
PR48 (placebo + peginterferon alfa-2a + ribavirin x 12 wks, then peginterferon alfa-2a + ribavirin x 36 wks), T12PR24 (telaprevir + peginterferon alfa-2 + ribavirin x 12 wks, then peginterferon alfa-2 + ribavirin x 12 wks), T12PR48 (telaprevir + peginterferon alfa-2 + ribavirin x 12 wks, then peginterferon alfa-2 + ribavirin x 36 wks), or T12PR12 (telaprevir + peginterferon alfa-2a + ribavirin x 12 wks) Dosing: telaprevir 1250 mg x 1, then 750 mg q8h; peginterferon alfa-2a 180 μg/wk; ribavirin 1000 or 1200 mg/day |
SVR rates: PR48 group: 41% T12PR24 group: 61% (p=0.02 vs PR48) T12PR48 group: 67% (p=0.002 vs PR48, p=0.51 vs T12PR24) T12PR12 group: 35% |
Phase IIb, randomized, partially double-blind, placebo-controlled, multicenter (PROVE2) (n=334)28
|
Genotype 1, treatment-naïve |
PR48 (placebo + peginterferon alfa-2a + ribavirin x 12 wks, then peginterferon alfa-2a + ribavirin x 36 wks), T12PR24 (telaprevir + peginterferon alfa-2 + ribavirin x 12 wks, then peginterferon alfa-2 + ribavirin x 12 wks), T12PR12 (telaprevir + peginterferon alfa-2a + ribavirin x 12 wks, or T12P12 (telaprevir + peginterferon alfa-2a x 12 wks) Dosing: telaprevir 1250 mg x 1, then 750 mg q8h; peginterferon alfa-2a 180 μg/wk; ribavirin 1000 or 1200 mg/day |
SVR rates: PR48 group: 46% T12PR12 and T12P12 groups combined: 48% (p=0.89 vs PR48) T12PR24 group: 69% (p=0.004 vs PR48) T12P12 group: 36% (p=0.20 vs PR48) T12PR12 group: 60% (p=0.12 vs PR48, p=0.003 vs T12P12) |
Phase IIb, randomized, partially placebo-controlled, partially double-blind, multicenter (PROVE3) (n=465)29
|
Genotype 1, treatment-experienced |
PR48 (placebo + peginterferon alfa-2a + ribavirin x 24 wks, then peginterferon alfa-2a + ribavirin x 24 wks), T12PR24 (telaprevir + peginterferon alfa-2a + ribavirin x 12 wks, then placebo + peginterferon alfa-2a + ribavirin x 12 wks), T24PR48 (telaprevir + peginterferon alfa-2a + ribavirin x 24 wks, then peginterferon alfa-2a + ribavirin x 24 wks), or T24P24 (telaprevir + peginterferon alfa-2a x 24 wks) Dosing: telaprevir 1125 mg x 1, then 750 mg q8h; peginterferon alfa-2a 180 μg/wk; ribavirin 1000 or 1200 mg/day |
SVR rates: PR48 group: 14% T12PR24 group: 51% (p<0.001 vs PR48) T24PR48 group: 53% (p<0.001 vs PR48) T24P24 group: 24% (p=0.02 vs PR48) |
Phase II, randomized, open-label (n=166)23
|
Genotype 1, treatment-naïve |
Group A (telaprevir 750 mg q8h + peginterferon alfa-2a + ribavirin), group B (telaprevir 750 mg q8h + peginterferon alfa-2b + ribavirin), group C (telaprevir 1125 mg q12h + peginterferon alfa-2a + ribavirin), or group D (telaprevir 1125 mg q12h + peginterferon alfa-2b + ribavirin) Dosing: peginterferon alfa-2a 180 μg/wk; peginterferon alfa-2b 1.5 μg/kg/wk; ribavirin 1000 or 1200 mg/day with peginterferon alfa-2a; ribavirin 800 or 1200 mg/day with peginterferon alfa-2b |
SVR rates: Group A: 85.0% Group B: 81.0% Group C: 82.5% Group D: 82.1% (p>0.787 for differences between each group) |
Phase IIa, randomized, partially blinded (study C209) (n=49)30
|
Genotypes 2 and 3, treatment-naïve |
Group A (telaprevir alone), group B (telaprevir + peginterferon alfa-2a + ribavirin), or group C (placebo + peginterferon alfa-2a + ribavirin) x 14 days, followed by peginterferon + ribavirin through wk 24 Dosing: telaprevir 750 mg q8h; peginterferon alfa-2a 180 μg/wk; ribavirin 800 mg/day |
SVR rates, genotype 2: Group A: 56%; group B: 100%; group C: 89% SVR rates, genotype 3: Group A: 50%; group B: 67%; group C: 44% |
Phase IIa, randomized, partially blinded (study C210) (n=24)31
|
Genotype 4, treatment-naïve |
Group A (telaprevir alone), group B (telaprevir + peginterferon alfa-2a + ribavirin, or group C (placebo + peginterferon alfa-2a + ribavirin) x 14 days, followed by peginterferon alfa-2a + ribavirin x 46 wks Dosing: telaprevir 750 mg q8h; peginterferon alfa-2a 180 μg/wk; ribavirin 1000 or 1200 mg/day |
SVR rates: Group A: 63% Group B: 50% Group C: 63% |
Phase IIa, randomized, placebo-controlled, multicenter, 2-part (study 110) (n=60)32
|
HIV + HCV coinfection, genotype 1, naïve to HCV therapy |
Telaprevir + peginterferon alfa-2a + ribavirin x 12 wks, followed by peginterferon alfa-2a + ribavirin x 36 wks; or peginterferon alfa-2a + ribavirin x 48 wks (control) Dosing: telaprevir 750 mg q8h (1125 mg q8h if with efavirenz); peginterferon alfa-2a 180 μg/wk; ribavirin 1000 or 1200 mg/day (in France and Germany) or 800 mg/day (at all other institutions) |
Interim results (n=59): Telaprevir vs control: HCV RNA < 25 IU/ml at wk 12: 68% vs 14% HCV RNA < 25 IU/ml at wk 4: 70% vs 5% |
Phase III, randomized, open-label (ILLUMINATE) (n=540)33
|
Genotype 1, treatment-naïve |
Telaprevir + peginterferon alfa-2a + ribavirin x 12 wks, then peginterferon alfa-2a + ribavirin alone x 8 wks; if HCV RNA < 25 IU/ml (eRVR) at wks 4 and 20, patients were randomized 1:1 to continue peginterferon alfa-2a + ribavirin until wk 24 or 48; if HCV RNA ≥ 25 IU/ml (no eRVR) at wks 4 and 20, patients continued peginterferon alfa-2 + ribavirin until wk 48 Dosing: telaprevir 750 mg q8h; peginterferon alfa-2a 180 μg/wk; ribavirin 1000 or 1200 mg/day |
SVR rates in patients who achieved eRVR: 24-wk group: 92% 48-wk group: 87.5% (change of 4.5%, 95% CI –2.1–11.1%) |
Phase III, randomized, double-blind, placebo-controlled, multicenter (ADVANCE) (n=1095)34
|
Genotype 1, treatment-naïve |
Telaprevir + peginterferon alfa-2a + ribavirin x 8 wks or 12 wks, then if eRVR was achieved, peginterferon alfa-2a + ribavirin x 16 or 12 wks, respectively (total of 24 wks of therapy); if eRVR was not achieved, a total of 48 wks of peginterferon alfa-2a + ribavirin therapy was administered; control group received placebo + peginterferon alfa-2a + ribavirin x 12 wks, followed by peginterferon alfa-2a + ribavirin x 36 wks Dosing: telaprevir 750 mg q8h; peginterferon alfa-2a 180 μg/wk; ribavirin 1000 or 1200 mg/day |
SVR rates: 8-wk telaprevir group: 69% 12-wk telaprevir group: 75% Control group: 44% (p<0.0001 for each telaprevir group vs control) |
Phase III, randomized, open-label (ILLUMINATE) (n=540)33
|
Genotype 1, treatment-naïve |
Telaprevir + peginterferon alfa-2a + ribavirin x 12 wks, then peginterferon alfa-2a + ribavirin alone x 8 wks; if HCV RNA < 25 IU/ml (eRVR) at wks 4 and 20, patients were randomized 1:1 to continue peginterferon alfa-2a + ribavirin until wk 24 or 48; if HCV RNA ≥ 25 IU/ml (no eRVR) at wks 4 and 20, patients continued peginterferon alfa-2 + ribavirin until wk 48 Dosing: telaprevir 750 mg q8h; peginterferon alfa-2a 180 μg/wk; ribavirin 1000 or 1200 mg/day |
SVR rates in patients who relapsed after previous therapy: PR48: 24%; T12PR48: 83% (p<0.0001 vs PR48); lead-in T12PR48: 88% (p<0.001 vs PR48) SVR rates in nonresponders to previous therapy: PR48: 9%; T12PR48: 41% (p<0.0001 vs PR48); lead-in T12PR48: 41% (p<0.001 vs PR48) SVR rates in "null responders" to previous therapy: PR48: 5%; T12PR48: 29% (p<0.0001 vs PR48); lead-in T12PR48: 33% (p<0.001 vs PR48) SVR rates in partial responders to previous therapy: PR48: 15%; T12PR48: 59% (p<0.0001 vs PR48); lead-in T12PR48: 54% (p<0.001 vs PR48) |
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