Design Objective SVR 12 HCV RNA lt 25 IUml with 95 CI in treatmentnaïve genotyp e 1 treated for 12 weeks DCV SOF 400 mg QD DCV SOF 400 mg QD Randomisation 2 1 Openlabel ID: 623763
Download Presentation The PPT/PDF document "ALLY-2" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
ALLY-2
Design
Objective
SVR
12
(HCV RNA < 25 IU/ml), with 95% CI, in treatment-naïve genotype 1 treated for 12 weeks
DCV + SOF 400 mg QD
DCV + SOF 400 mg QD
Randomisation*2 : 1Open-label
ALLY-2 Study: DCV + SOF for HCV in HIV co-infection
W8
N = 52
≥ 18 years
Chronic HCV infection Genotypes 1 to 6Treatment-naïve or experienced,NS5A inhibitor-naïveHCV RNA ≥ 10,000 IU/mlCompensated cirrhosis** allowedHIV infection on ART** and HIV RNA < 50 c/ml and CD4 ≥ 100/mm3,or no ART and CD4 ≥ 350/mm3
Wyles DL. N Engl J Med. 2015 Aug 20;373(8):714-25.
Treatment-experienced
N = 101
Treatment naïve
* Metavir F4 on biopsy, or Fibroscan > 14.6 kPa, or Fibrotest® > 0.74 + APRI > 2
*** Permitted ARV : PI/r, NRTI, NNRTI, INSTI, MVC
W12
DCV +
SOF 400 mg QD
N = 50
No
randomisation
Open-label
DCV QD : 60 mg, 30 mg with PI/r, 90 mg with NNRTI other than RPV
* Randomisation
was
stratified
on
cirrhosis
(
yer
or no) and
genotypeSlide2
Naïve 12W
N = 101
Naïve 8W
N = 50
Experienced 12W
N = 52
Median age, years
52
51
57
Female
9%
16%
17%Genotype
1a1b
2
3
4
70%
12%
11%
6%
1%
70%
12%
12%
6%
0
63%
21%
4%
8%4%HCV RNA, log10 IU/ml, median6.76.46.7Cirrhosis9%10%29%HIV RNA < 50 c/ml94%94%96%CD4/mm3, median520575636PI/r : DRV/r / ATV/r / LPV/r19% / 19% / 9%44% / 10% / 6%22% / 24% / 0NNRTI : EFV / NVP / RPV18% / 5% / 5%17% / 2% / 2%16% / 6% / 2%Other : RAL / DTG / NRTI only22% / 3% / 017% / 2% / 020% / 8% / 4%Post-treatment W12 missing (LTFU)110
Baseline characteristics and patient disposition
ALLY-2
ALLY-
2
Study: DCV + SOF for HCV in HIV co-infection
Wyles
DL. N
Engl
J Med. 2015 Aug 20;373(8):714-25.Slide3
SVR
12
(HCV RNA < 25 IU/ml)
Naïve 12W
Naïve 8W
Experienced 12W
* All other genotypes : SVR12 = 100% in naïve 12W and experienced 12WSVR12 : 100% with 12 weeks of DCV + SOF, with all NNRTI and PI/r, except DRV/r (95% in naïve 12W, 91% in experienced)
ALLY-2ALLY-2 Study: DCV + SOF for HCV in HIV
co-infection25
50
100
75
96
76%
98
97(91.6-99.4)
76
(62-87)
98.1
(89.7-100)
89
93
98
100
98
95
96
Baseline HCV RNA
log
10
IU/ml
YesNo< 6 MAll (N = 203) Genotype 1 (N = 168)≥ 6 MCirrhosisGenotype 1a*9797100N834144101505291590344371583333190Wyles DL. N Engl J Med. 2015 Aug 20;373(8):714-25.Slide4
SVR
12
(HCV RNA < 25 IU/ml) with 8 weeks of DCV + SOF
ALLY-2
ALLY-
2 Study: DCV + SOF for HCV in HIV co-infection25
5010075
76
%
76
67
60
77
69N415021
544Baseline HCV RNA
log10 IU/ml
Yes
No
< 6 M
All
Genotype 1
≥ 6 M
Cirrhosis
79
88
80
82
8
10
11
ARV regimen
DRVOtherPINNRTIOther16340Wyles DL. N Engl J Med. 2015 Aug 20;373(8):714-25.Slide5
NS5B
RAVs at baseline in 1/39 tested patients (C316H + V321I) 17% (33/198) of baseline sequences had NS5A polymorphisms at positions 28, 30, 31 or 93
Resistance data
SVR12 (n/N)*
With baseline NS5A RAVs
Without baseline NS5A RAVs
12-week groups96% (22/23)98% (122/125)
8-week group67% (6/9)
78% (31/40)Similar SVR12 rates in patients with or without baseline NS5A RAVs
12 patients with relapse 10 in 8-week arm, 9/10 with concomitant DRV/r2/10 relapses had baseline NS5A RAVs, 1 of which had also NS5B-V321I RAV1/10 relapses in 8-week arm had an emergent NS5A RAV at time of failure (Q30E) No other RAVs emergence at failure in the remaining 6 cases
2 in 12-week arm1 had a NS5A RAV at baseline and failure (Y93N), and NS5B-L159F variant at failure
1 had emergence of NS5A-Q30R at failure
ALLY-2
ALLY-2 Study: DCV + SOF for HCV in HIV co-infectionWyles DL. N Engl J Med. 2015 Aug 20;373(8):714-25.Slide6
12-Week Groups
N = 153
8-Week Group
N = 50
Death
0
1 (2%), unrelated
Serious adverse event4 (3%), unrelated
0AEs leading
to discontinuation
0
0
Grade 3-4 laboratory abnormalities
INR > 2 x ULN2 (1%)
0
ALT
> 5 x ULN
0
0
AST
> 5 x ULN
0
1 (2%)
Total bilirubin
> 2.5 x ULN (all on ATV/r)
7 (5%)
1(2%)
Lipase
> 3.0 x ULN6 (4%)1 (2%)Adverse events and Grade 3-4 laboratory abnormalities, N (%)ALLY-2ALLY-2 Study: DCV + SOF for HCV in HIV co-infection2 HIV virologic failure, 1 unconfirmed with treatment discontinuation, 1 with HIV resuppressed with no ART adjustmentWyles DL. N Engl J Med. 2015 Aug 20;373(8):714-25.Slide7
12-Week Naïve
N = 101
12-Week Experienced
N = 52
8-Week Naïve
N = 50
Fatigue19%19%
8%Nausea
14%
15%
8%
Headache
12%
15%6%Diarrhea
11%
6%
2%
Vomiting
6%
6%
2%
Rash
6%
6%
0
Insomnia
5%
6%
0
Abdominal pain
5%
2%2%Cough3%2%6%Dizziness1%6%4%Constipation3%6%0Clinical adverse events reported in ≥ 5% of patients in any group (%)ALLY-2ALLY-2 Study: DCV + SOF for HCV in HIV co-infectionWyles DL. N Engl J Med. 2015 Aug 20;373(8):714-25.Slide8
ALLY-
2 Study: DCV + SOF for HCV in HIV
co-infectionSummary
After 12 weeks of DCV + SOF in HIV/HCV coinfected patients, the overall SVR12 was 97% 97% in GT 1 ; 100% in GT 2, 3, and 497% in treatment-naive and 98% in treatment-experienced patients
No significant effect of race, baseline HCV RNA levels, cirrhosis or ARV regimenIn patients treated for 8 weeks with DCV + SOF, SVR
12 was 76%Increased relapse in coinfected patients with shorter therapy, higher baseline HCV RNA (≥ 2M IU/ml), and DRV/r-based cART with DCV 30 mg QDNo compromise of HIV suppression and no modification of on-treatment ARV regimens due to DCV + SOFDCV + SOF was safe and well tolerated, offers a predictable drug-drug interaction profile with flexibility to dose adjust, and is compatible with a wide range of antiretrovirals
ALLY-2Wyles DL. N
Engl J Med. 2015 Aug 20;373(8):714-25.