Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give...
Transcript of Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give...
![Page 1: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/1.jpg)
Supplementary Appendix
This appendix has been provided by the authors to give readers additional information about their work.
Supplement to: Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. DOI: 10.1056/NEJMoa1512612
![Page 2: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/2.jpg)
1
Supplementary Appendix
This appendix has been provided by the authors to give readers additional information about
their work.
Supplement to: Graham Foster, Nezam Afdhal, Stuart K. Roberts, et al. Sofosbuvir and
Velpatasvir for HCV Genotype 2 and 3 Infection
![Page 3: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/3.jpg)
2
Table of contents
ASTRAL-2 Study Investigators 3
ASTRAL-3 Study Investigators 4
Table S1. ASTRAL-2: Reasons for screen failure 5
Table S2. ASTRAL-3: Reasons for screen failure 6
Figure S1. Patient disposition: ASTRAL-2 7
Figure S2. Patient disposition: ASTRAL-3 8
Table S3. SVR12 in patient subgroups of ASTRAL-3 9
Table S4. Characteristics of patients receiving SOF-VEL in ASTRAL-3 who did not achieve SVR 11
Figure S3. Rates of SVR12 by baseline resistance-associated variants in ASTRAL-3 12
Table S5. Serious adverse events in ASTRAL-2 13
Table S6. Serious adverse events in ASTRAL-3 14
![Page 4: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/4.jpg)
3
ASTRAL-2 Study Investigators
United States
Nezam Afdhal, Ritu Agarwal, M. Tarek Al-Assi, Michael Bennett, David Bernstein, Raj
Bhandari, Norbert Bräu, Stuart Cohen, Mitchell Davis, Adrian Di Bisceglie, Kyle Etzkorn,
Gregory Everson, Jeffrey Fessel, Steven Flamm, Reem Ghalib, Norm Gitlin, Elliot Godofsky,
Stuart Gordon, William Harlan, Trevor Hawkins, Robert Herring, Federico Hinestrosa, Ira
Jacobson, Eric Lawitz, Anne Luetkemeyer, Giuseppe Morelli, Timothy Morgan, Anders Nyberg,
Neville Pimstone, David Pound, Nancy Reau, Rajender Reddy, Maribel Rodriguez-Torres,
Sergio Rotjer, Peter Ruane, Vinod Rustgi, Michael Ryan, Arun Sanyal, Eugene Schiff, Thomas
Sepe, Obaid Shaikh, Aasim Sheikh, Mitchell Shiffman, Mark Sulkowski, Paul Thuluvath, Myron
Tong, William Towner, Tram Tran, Kimberly Workowski, David Wyles, Ziad Younes
![Page 5: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/5.jpg)
4
ASTRAL-3 Study Investigators
Australia
Wendy Cheng, Greg Dore, Barbara Leggett, Lindsay Mollison, Stephen Pianko, Stuart Roberts,
Simone Strasser, Alexander Thompson,
Canada
Brian Conway, Curtis Cooper, Jordan Feld, Stephen Shafran, Mark Swain, Bernard Willems,
Eric Yoshida
France
Armand Abergel, Laurent Alric, Tarik Asselah, Marc Bourlière, Victor De Ledinghen,
Christophe Hézode, Véronique Loustaud-Ratti, Philippe Mathurin, Stanislas Pol, Didier Samuel,
Fabien Zoulim
Germany
Keikawus Arastéh, Thomas Berg, Guido Gerken, Tobias Goeser, Norbert Gruener, Michael
Manns, Stefan Mauss, Jorg Petersen, Stefan Zeuzem
Italy
Alessandra Mangia, Francesco Mazzotta
New Zealand
Edward Gane, Catherine Stedman
United Kingdom
Kosh Agarwal, Richard Aspinall, Ashley Brown, Jane Collier, Matthew Cramp, Daniel Forton,
Graham Foster, Ray Fox, William Rosenberg, Stephen Ryder, Andrew Ustianowski
United States
Nezam Afdhal, Michael Bennett, Norbert Bräu, Stuart Cohen, Mitchell Davis, Kyle Etzkorn,
Gregory Everson, Steven Flamm, Stuart Gordon, Federico Hinestrosa, Ira Jacobson, Eric Lawitz,
Giuseppe Morelli, Keyur Patel, David Pound, K. Rajender Reddy, Maribel Rodriguez-Torres,
Michael Ryan, Eugene Schiff, Obaid Shaikh, Aasim Sheikh, Mitchell Shiffman, Mark
Sulkowski, William Towner, Tram Tran, Ziad Younes
![Page 6: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/6.jpg)
5
Table S1. Reasons for screen failure: ASTRAL-2
![Page 7: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/7.jpg)
6
Table S2. Reasons for screen failure: ASTRAL-3
![Page 8: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/8.jpg)
7
Figure S1. Patient disposition: ASTRAL-2
317 screened
269 randomized
135 randomized to receive sofosbuvir-velpatasvir
134 randomized to receive sofosbuvir-ribavirin
134 began treatment 132 began treatment
133 completed treatment
134 assessed for efficacy
131 completed treatment
132 assessed for efficacy
1 discontinued treatment due to adverse event 1 discontinued treatment: LTFU
48 were not randomized 45 did not meet eligibility criteria 1 withdrew consent 1 were lost to follow-up 1 outside visit window
1 did not begin treatment 2 did not begin treatment
![Page 9: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/9.jpg)
8
Figure S2. Patient disposition: ASTRAL-3
652 screened
558 randomized
278 randomized to receive sofosbuvir-velpatasvir
280 randomized to receive sofosbuvir-ribavirin
277 began treatment 275 began treatment
275 completed treatment
277 assessed for efficacy
254 completed treatment
275 assessed for efficacy
2 discontinued treatment 1 due to lack of efficacy 1 non-adherence
21 discontinued treatment: 9 adverse event 4 lost to follow-up 3 withdrew consent 2 death
2 non-compliance with study drug 1 lack of efficacy
94 were not randomized 87 did not meet eligibility criteria 6 withdrew consent 1 study enrolment was closed
1 did not begin treatment 5 did not begin treatment
![Page 10: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/10.jpg)
9
Table S3. SVR12 in patient subgroups of ASTRAL-3
![Page 11: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/11.jpg)
10
Table S3. SVR12 in patient subgroups of ASTRAL-3 (continued)
*One patient with HCV genotype 3 had previously received telaprevir with pegylated interferon and ribavirin.
*
(
![Page 12: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/12.jpg)
11
Table S4. Characteristics of patients receiving sofosbuvir-velpatasvir who relapsed in ASTRAL-3
Age Sex Race BMI Geno-type
Cirrhosis IL28B HCV RNA
Timing of VF
HCV treatment history
Resistance-associated variants
NS5A NS5B
BL FU wk 12 BL FU wk12
53 F White 23.7 3a Yes CC 6.9 FU wk 4 Naive Y93H (15.2%) Y93H (>99%) None None
58 M White 24.6 3a Yes CC 6.3 FU wk 12 Experienced None Y93H (>99%) None None
61 M White 25.2 3a Yes CT 6.0 FU wk 12 Naïve Y93H (>99%) Y93H (>99%) None None
61 M White 21.7 3a No TT 5.5 FU wk 4 Experienced None Y93H (>99%) None None
50 M White 28.7 3a No CT 6.5 FU wk 4 Naïve Y93H (>99%) Y93H (>99%) None None
56 M White 26.7 3a Yes TT 6.1 FU wk 4 Experienced None Y93H (>99%) None None
45 M White 30.6 3 No CC 6.9 FU wk 4 Experienced Y93H (2.8%) Y93H (>99%) None None
46 M White 23.9 3a Yes CT 6.1 FU wk 4 Experienced A30K (>99%) A30K (>99%) Y93H (97.2%)
None None
57 M White 26.8 3a Yes CT 6.3 FU wk 4 Naïve None Y93H (>99%) None None
56 M White 28.1 3a Yes CT 6.3 FU wk 4 Experienced None Y93H (>99%) None None
39 M White 22.4 3a No CC 6.6 FU wk 12 Experienced None GT1a reinfection
F denotes female; M male; BMI body mass index; VF virologic failure; BL baseline; FU follow-up.
![Page 13: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/13.jpg)
12
Figure S3. Rates of sustained virologic response by baseline NS5A resistance-associated
variants (1% cutoff) in ASTRAL-3
Legend: Figures show rates of SVR12 in patients with and without NS5A resistance-associated
variants at baseline. Figure S3A shows results in patients with any NS5A resistance-associated
variant. Figure S3B shows results in patients with the Y93H NS5A resistance-associated variant
at baseline.
Figure S3A. Overall
Figure S3B. By the Y93H NS5A resistance-associated variant (1% cutoff)
![Page 14: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/14.jpg)
13
Table S5. Serious adverse events in ASTRAL-2
![Page 15: Supplementary AppendixSupplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Foster GR, Afdhal](https://reader034.fdocuments.in/reader034/viewer/2022050604/5fabd6e1dd26f84abe467141/html5/thumbnails/15.jpg)
14
Table S6. Serious adverse events in ASTRAL-3