SD1000: High Sustained Viral Response Rate in 1361 Patients With Hepatitis C Genotypes 1, 2, 3, and 4 Using a Low-cost, Fixed-dose Combination Tablet of Generic Sofosbuvir and Daclatasvir: A Multicenter, Phase III Clinical Trial
Authors: Merat Shahin ,   SD1000 Research Team, Merat Shahin , Sharifi Amir-Houshang , Poustchi Hossein , Hajiani Eskandar , Gharavi Abdolsamad , Karimi Jalal , Mansour-Ghanaei Fariborz , Fattahi Mohammad-Reza , Ahmadi Lida , Somi Mohammad-Hossein , Kalantari Hamid , Ghadir Mohammad-Reza , Sheikhesmaeili Farshad , Baniasadi Nadieh , Sohrabi Masoudreza , Moosavy Seyedhamid , Ziaee Masood , Zahedi Mohammad-Javad , Mokhtare Marjan , Sali Shahnaz , Sayad Babak , Afshar Behrooz , Bakhshipour Alireza , Parsi Abazar , Sharifian Afsaneh , Amiriani Taghi , Malekzadeh Zeinab , Merat Dorsa , Ganji Azita , Rahmani-Samani Fereidoun , Jamali Raika , Sofian Masoomeh , Ghezlou Mohammad , Ali Sohrabpour Amir , Goshayeshi Ladan , Valizadeh-Toosi Seyed-Mohammad , Eslami Layli , Maleki Iradj , Hormati Ahmad , Shayesteh Ali-Akbar , Shayesteh Elahe , Norouzi Alireza , Abna Zahra , Janbakhsh Alireza , Fakheri Hafez , Minakari Mohammad , Sardarian Hossein , Fallah Ghajary Adel , Fattahi-Abdizadeh Mojtaba , Latifnia Maryam , Roozbeh Fatemeh , Agah Shahram , Fakhrieh-Asl Saba , Nateghi-Baygi Alireza , Fattahi Babak , Nateghi-Baygi Helia , Hill Andrew , Malekzadeh Reza 
Published: July 2019

Background

The combination of sofosbuvir and daclatasvir is a potent, pangenotypic regimen suitable for mass-scale hepatitis C treatment, especially in resource-limited countries where newer, expensive combinations are not available. This combination has been widely tested on genotype 4. However, Phase III trials of this combination in other genotypes have been cost prohibitive. With the introduction of generic, low-cost sofosbuvir and daclatasvir, large-scale studies in resource-limited countries are now possible.

Methods

Sofosbuvir at 400 mg and daclatasvir at 60 mg were coformulated into a fixed-dose combination (FDC) tablet (Sovodak, Rojan Pharma, Tehran, Iran). Patients from 46 centers were dosed for 12 or 24 weeks with or without ribavirin, in line with existing guidelines. Responses to treatment were evaluated 12 weeks after the end of treatment (for a sustained virological response at Week 12; SVR12).

Results

There were 1361 patients recruited. Overall, the patients were 21% female, with a mean age of 50 years; 39% were cirrhotic; 22% were treatment-experienced; 47% were genotype 1, 41% were genotype 3, and 2% were other genotypes. The genotype was not known in 10% of the patients. The intention-to-treat and per-protocol SVR12 rates were 94.7% and 98.8%, respectively. The safety profile was unremarkable, treatment was well tolerated, and compliance with the single-tablet regimen was excellent.

Conclusions

The treatment with FDC of sofosbuvir and daclatasvir achieved high SVR12 rates, equivalent to those seen in Phase III trials of other pangenotypic options, and has been conducted at a similar scale in a representative, real-world population at a cost of under $100 per patient, which makes this combination suitable for elimination protocols in resource-limited countries.

Clinical Trials Registration

NCT03200184.