Clinical Study Data Request Registered Users, Please Login


Proposal 1085

Title of the Proposed Research

Optimized peg-interferon alpha-2a Treatment of Hepatitis C and Hepatitis B

Lead Researcher

Mohammad I Saleh, PhD

Affiliation

Faculty of Pharmacy
University of Jordan
Amman, JO

Funding Source

The funding for the PhD project is provided jointly be the Centre for Bayesian Statistics in Health Economics (CHEBS) and the School of Mathematics and Statistics (SoMaS) at the University Of Sheffield.

Potential Conflicts of Interest

None

Data Sharing Agreement Date

10 February 2015

Lay Summary

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are serious global health problems. According to WHO fact sheets, 2 billion people infected HBV worldwide, and 350 million suffering from chronic HBV infection. Similarly, HCV infection has an estimated prevalence of 2.35 per cent in 2011 (160 million chronically infected individuals).

Peg-interferon alpha-2a (Peg-IFN-a 2a) is effective antiviral drug for chronic liver diseases. However, it is associated with a number of side effects, including mild thrombocytopenia. The usual protocol to treat Peg-IFN-a 2a related thrombocytopenia is to reduce the Peg-IFN-a 2a dose if platelet count falls to < 30 × 109/L. Interferon therapy should be discontinued if platelet count falls to < 20 × 109/L. This leads to dose modification in approximately 19% of cases and discontinuation in 2% of cases. Peg-IFN-a 2a combined with a low dose of ribavirin is more effective than conventional interferon combined with a low dose of ribavirin. However, a significant number of patients fail to respond to respond to Peg-IFN-a 2a.

The objective of the present project is to develop an optimal dosing algorithm of Peg-IFN-a 2a. Two models will be formulated: 1) A model that describe the antiviral response to Peg-IFN-a 2a treatment (described using various response markers such as aminotransferase levels, antigen-antibody HBV profile, and viral load) and 2) A model that describe the change in platelet level following Peg-IFN-a 2a treatment. These models will be used to will identify the pharmacokinetic /pharmacodynamic (PK/PD) and physiologic factors important in predicting and maximizing Peg-IFN-a 2a’s effect in the treatment of Hepatitis B and Hepatitis C infections. We also identify factors that minimize the incidence of thrompocytopenia and hence avoid Peg-IFN-a 2a dose reduction or discontinuation. The model can also be used to identify predictors of non-responders to Peg-IFN-a 2a treatment so early measures can be taken to improve therapeutic outcomes. This project is expected to improve patient care by identifying proper treatment strategies and (sub)populations that may (or may not) benefit from Peg-IFN-a 2a. Additionally, and hence avoid antiviral therapy discontinuation.

Study Data Provided

Roche Study NV16037: A phase II open label study evaluating safety and efficacy of PEG-Interferon alpha-2a (PEG-IFN, Ro 25-8310) versus Interferon (IFN alpha-2a, Roferon-A) in interferon have patients with chronic hepatitis B.
Roche Study WV16240: A phase III partially double blind study evaluating the efficacy and safety of 40KD branched pegylated interferon alfa-2a (PEG-IFN, RO0258310) combined with placebo or lamivudine versus lamivudine in HBeAg positive patients with chronic hepatitis B.
Roche Study WV16241: A phase III partially double blinded study evaluating the efficacy and safety of 4okD branched pegylated inteferon alfa-2a (PEG-IGFN, Ro 25-8310) combined with placebo or lamivudine versus lamivudine in anti-HBe positive patients with chronic hepatitis B
Roche Study WV19432: A randomized, double-blind study of the effect of treatment duration and dose of PEGASYS on HBeAg seroconversion and safety in patients with HBeAg positive chronic hepatitis B.
Roche Study NV15942: A phase III, randomized, multicenter, efficacy and safety study examining the effects of the duration of treatment and the daily dose of ribavirin in patients with chronic hepatitis C virus infection treated with the combination of pegylated-interferon alpha-2a and ribavirin.
Roche Study NV15801: A phase III, randomized, multicenter, efficacy and safety study comparing the combination of PEG-IFN alfa-2a (Ro 25-8310) and ribavirin to IFN alfa-2b and ribavirin in the treatment of patients with chronic hepatitis C

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation