Isabelle Andrieux-Meyer1, Soek-Siam Tan2, Sombat Thanprasertsuk3, Nicolas Salvadori4, Caroline Menétrey5, François Simon5, Tim R Cressey6, Hajjah Rosaida Hj Mohd Said7, Muhammad Radzi Abu Hassan8, Haniza Omar2, Hoi-Poh Tee9, Wah Kheong Chan10, Suresh Kumar11, Satawat Thongsawat12, Kanawee Thetket13, Anchalee Avihingsanon14, Suparat Khemnark15, Sabine Yerly16, Nicole Ngo-Giang-Huong17, Sasikala Siva18, Alistair Swanson5, Vishal Goyal19, Francois Bompart5, Bernard Pécoul5, Shahnaz Murad20. 1. Drugs for Neglected Diseases initiative, Geneva, Switzerland. Electronic address: Switzerlandiandrieux-meyer@dndi.org. 2. Department of Hepatology, Selayang Hospital, Batu Caves, Malaysia. 3. Department of Disease Control, Ministry of Public Health, Bangkok, Thailand. 4. Public Health Promotion Research and Training-Institut de Recherche pour le Développement, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand. 5. Drugs for Neglected Diseases initiative, Geneva, Switzerland. 6. Public Health Promotion Research and Training-Institut de Recherche pour le Développement, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK. 7. Gastroenterology & Hepatology Unit, Ampang Hospital, Ampang Jaya, Malaysia. 8. Gastroenterology Unit, Medical Department, Hospital Sultanah Bahiyah, Alor Setar, Malaysia. 9. Gastroenterology Unit, Medical Department, Hospital Tengku Ampuan Afzan, Kuantan, Malaysia. 10. Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 11. Infectious Disease Unit, Medical Department, Hospital Sungai Buloh, Selangor, Malaysia. 12. Department of Internal Medicine, Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand. 13. Internal Medicine unit, Medical Department, Nakornping Hospital, Chiang Mai, Thailand. 14. HIV-Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Tuberculosis Research Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 15. Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand. 16. Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland. 17. Public Health Promotion Research and Training-Institut de Recherche pour le Développement, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Laboratory of Virology, Program for HIV Prevention and Treatment L'Institut de Recherche pour le Développement, Chiang Mai, Thailand. 18. Drugs for Neglected Diseases initiative, Kuala Lumpur, Malaysia. 19. Drugs for Neglected Diseases initiative, New York, NY, USA. 20. Ministry of Health, Kuala Lumpur, Malaysia.
Abstract
BACKGROUND: In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV. METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183. FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment. INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality. FUNDING: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.
BACKGROUND: In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV. METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183. FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment. INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality. FUNDING: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.
Authors: Kevin McFarthing; Gary Rafaloff; Marco Baptista; Leah Mursaleen; Rosie Fuest; Richard K Wyse; Simon R W Stott Journal: J Parkinsons Dis Date: 2022 Impact factor: 5.520