Clinical Trials

Date: 2014-03-04

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the 21th Conference on Retroviruses and Opportunistic Infections (CROI)

Company: BMS (USA) Medivir (Sweden)

Product: simeprevir (TMC435) and daclatasvir

Action mechanism:

• direct-acting antiviral agent/protease inhibitor/RNA polymerase (NS5A) inhibitor/RNA polymerase (NS3A) inhibitor. Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir.Simeprevir is a once daily potent HCV NS3/4A protease inhibitor in phase III clinical development for the treatment of chronic hepatitis C jointly developed by Medivir and Janssen Research & Development Ireland. Daclatasvir is a BMS' investigational NS5A replication complex inhibitor.

Disease: treatment-naïve or previous null responder patients with Hepatitis C Virus (HCV) genotype 1a and 1b

Therapeutic area: Infectious diseases

Country:

Trial details:

• In this open label phase II study the potential to achieve sustained viral response (SVR), 12 (SVR12) and 24 (SVR24) weeks post treatment in treatment-naïve and null responder patients infected with HCV genotype 1a and 1b will be evaluated. The study will include approx. 180 patients and will evaluate a combination of TMC435 and daclatasvir, with or without Ribavirin, in four different cohorts for 12 or 24 weeks of treatment. Cohort one and two will include patients with genotype 1b where TMC435 and daclatasvir will be dosed with or without Ribavirin for 12 weeks with a 36 weeks follow-up or for 24 weeks with a 24 weeks follow-up. Cohort three and four will include patients with genotype 1a where TMC435, daclatasvir and Ribavirin will be dosed for 12 or 24 weeks with a 24 weeks post treatment follow-up. Overall, patients were 92% white, 49% male, 21% cirrhotic, and 76% IL28B non-CC genotype and were well-balanced across treatment groups.

Latest news:

• • On March 4, 2014, Medivir has announced that study results from a phase IIa trial evaluating simeprevir in combination with daclatasvir, with and without ribavirin, in patients with hepatitis C (HCV) genotype 1 infection, have been presented at the 21th Conference on Retroviruses and Opportunistic Infections (CROI) on March 4th in Boston, USA. The study was conducted by BMS. Data from the study demonstrate that sustained virologic response 12 weeks after the end of treatment (SVR12) was reached in 75 to 85 percent of treatment-naïve patients and 65 to 95 percent of prior null responders with HCV genotype 1b after 12 or 24 weeks of treatment.
• In treatment-naïve HCV genotype 1b patients SVR12 was achieved by 75% (38/51) and 85% (45/53) when treated with simeprevir and daclatasvir, with or without ribavirin, respectively. In HCV genotype 1b prior null responders SVR12 was achieved by 95% (19/20) and 65% (15/23) with or without ribavirin, respectively. Estimated SVR12 rates in HCV genotype 1b patients (adjusted for pre-Week 12 discontinuations) were similar after 12 or 24 weeks of treatment in naive patients but higher after 12 than 24 weeks in prior null responders. In treatment-naïve HCV genotype 1a patients 67% (8/12) achieved SVR12. All HCV genotype 1a prior null responders were offered pegylated interferon alfa-2a in addition to ribavirin + daclatasvir + simeprevir as rescue therapy due to frequent on-treatment breakthroughs and were counted as treatment failures.
• The all-oral combination of daclatasvir plus simeprevir, with and without ribavirin, was generally well tolerated. There were two treatment-related serious adverse events (neurotoxicity, liver disorder) and one on-treatment death (unrelated trauma-associated intracranial hematoma). Three patients experienced treatment-related adverse events leading to discontinuation. Seventeen patients experienced grade 3/4 total bilirubin elevations without concurrent transaminase elevations, mostly in patients receiving ribavirin (14/17), consistent with ribavirin-induced hemolysis and known effects of simeprevir on bilirubin transporters.
• • On June 29, 2012, Medivir has announced that a phase II combination study with the investigational compound TMC435 and BMS' investigational compound daclatasvir will start in July. This study is part of the clinical collaboration agreement between Janssen R&D Ireland and Bristol-Myers Squibb Company announced on 2 December 2011 and on 18 April 2012. TMC435, a once daily potent NS3/4A protease inhibitor (PI) in phase III clinical development for the treatment of chronic genotype-1 hepatitis C virus (HCV) infection, will be investigated in an interferon free phase II trial in combination with Bristol-Myers Squibb´s investigational NS5A replication complex inhibitor, daclatasvir, also in phase III development. The purpose of this study is to assess the efficacy and safety of TMC435 and daclatasvir in combination with or without Ribavirin in chronic genotype-1 hepatitis C infected patients who are treatment-naive or null responders to previous Peginterferon alfa/Ribavirin therapy.

Is general: Yes