Paper # 146LB
Interim Analysis of a Phase 2a Double-blind Study of TVR in Combination with pegIFN-a2a and RBV in HIV/HCV Co-infected Patients
Mark Sulkowski*1, D Dieterich2, K Sherman3, J Rockstroh4, N Adda5, L Mahnke5, V Garg5, S Gharakhanian5, S McCallister5, and V Soriano6
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Mt Sinai Sch of Med, New York, NY, US; 3Univ of Cincinnati Coll of Med, OH, US; 4Univ of Bonn, Germany; 5Vertex Pharmaceuticals Inc, Cambridge, MA, US; and 6Hosp Carlos III, Madrid, Spain
Background: In the era of effective ART, hepatitis C
virus (HCV) disease is a major cause of morbidity and mortality in HIV-infected
patients. We investigated the safety, viral kinetics, and efficacy of treatment
with telaprevir (TVR) and pegylated interferon-alpha2a (pegIFN-α2a)/ribavirin
(RBV) in HIV/HCV genotype 1 co-infected interferon-naive patients: part A, no
concurrent ART; part B, stable, predefined ART with tenofovir (TDF)/emtricitabine
(FTC) with either efavirenz (EFV) or atazanavir (ATV)/ritonavir (r). The results
of a planned interim analysis are reported.
Methods: Patients in each part were randomized
into: TVR 750 mg every 8 hours + pegIFN-α2a 180 mg/week + RBV 800 mg/day for 12 weeks followed by 36 weeks of pegIFN-α2a
+ RBV (TVR/PR groups); and placebo + pegIFN-α2a/RBV for 48 weeks. TVR dose was
1125 mg every 8 hours when the ART regimen included EFV.
Results: This interim analysis was performed on 59
of the 60 dosed patients (part A, 13; part B, 46). Overall, 88% were male, 69%
white, mean age was 46 years, 68% had genotype 1a, 83% baseline HCV RNA
≥800,000 IU/mL, and 10% advanced liver fibrosis based on liver biopsy. Results
are shown in the table. Two patients in part B experienced HCV viral breakthrough.
Discontinuations due to adverse events occurred in 2 patients (3%) in the
TVR/PR groups vs 0 in the placebo group. Pruritus, nausea, vomiting, fever,
anorexia and dizziness were more frequent in patients who received TVR/PR than
in controls. No case of severe rash was seen. No significant changes in CD4
decrease or in HIV RNA level were observed in part B patients who received
either ART regimen compared to controls.
|
n, (%)
|
Part A
no ART
|
Part B
EFV/TDF/FTC
|
Part B
ATV/r +
TDF + FTC/3TC
|
Total
|
|
T/PR
n = 7
|
Control
n = 6
|
T/PR
n = 16
|
Control
n = 8
|
T/PR
n = 14
|
Control
n = 8
|
TPR
n = 37
|
Control
n = 22
|
|
Undetectable HCV RNA* at week
4
|
5 (71)
|
0 (0)
|
12 (75)
|
1 (12)
|
9 (64)
|
0 (0)
|
26 (70)
|
0 (0)
|
|
Undetectable HCV RNA* at week
12#
|
5 (71)
|
1 (17)
|
12 (75)
|
1 (12)
|
8 (57)
|
1 (12)
|
25 (68)
|
3 (14)
|
|
Undetectable HCV RNA* at weeks
4 and 12#
|
3 (43)
|
0 (0)
|
10 (62)
|
0 (0)
|
6 (43)
|
0 (0)
|
19 (49)
|
0 (0)
|
*as determined by Roche Taqman
v2, LLOQ of 25 IU/mL
#41 patients have reached week 12
Conclusions: In this interim analysis, substantially
more patients receiving a TVR-based regimen achieved undetectable HCV RNA at weeks
4 and 12. The safety and tolerability of TVR/PR was consistent with that
previously observed in HCV mono-infected patients; no novel adverse events were
detected. These data are encouraging for the treatment of HCV/HIV co-infected patients,
and the study is ongoing for assessment of sustained virologic response.
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