8th International Symposium on Hepatitis C and Related Viruses
September 2-5, 2001
Méridien Montparnasse
Paris, France
September 2-5, 2001
9:30am-4:30pm
Dr. Yoav Lurie
Poster Presentation
Session: Antiviral Development and Therapy
"Triple Combination Therapy With Histamine Dihydrochloride, Interferon
Alpha-2b (IFN) And Ribavirin For Chronic Hepatitis C Treatment Failures : 48 Week Results"
and from ICAAC:
(If Roche isn't interested in Bayer, what about S&P?)
Histamine Dihydrochloride and Interferon Alpha-2b as a Potential New Combination Therapy in Patients with Chronic Hepatitis C (HCV)
Y. LURIE1, K. GEHLSEN2; 1Kaplan Medical Center, Rehovot, Israel; 2Maxim Pharmaceuticals, San Diego, CA
Presentation Number: 751
Keywords: histamine dihydrochloride, hepatitis C, interferon alpha
Background: Oxidative stress in the liver induced by phagocyte-derived reactive oxygen species (ROS) down–regulate and suppresses NK and T cells. Histamine dihydrochloride inhibits the production and release of ROS, and potentiates activation of NK and T cells by cytokines. Aim: To evaluate the feasibility, safety and four-dose regimen of histamine as combination therapy with IFN alpha-2b in chronic HCV. Design: 129 IFN-naïve pts ages > 18 years with chronic HCV were enrolled in an international, multicenter, randomized phase II study. All pts received IFN alpha-2b (3 MIU, sc, TIW) and were randomized to one of four doses of histamine including 3, 5, 6, and 10 mg per week (Ceplene, 1 mg, sc, TIW; QD 5 x W; bid TIW; or bid QD 5 x W). Pts were treated for 12 wks; pts with complete or partial virological response were treated for additional 36 wks, and followed up at 72 wks. Complete virological response was defined as loss of detectable HCV RNA (Amplicor Monitor v. 2.0). Results: Baseline characteristics included: mean age 30 years, 67 (52%) pts with high viral load (HCV RNA > 2 million copies/ml), and 51 (40%) pts with HCV genotype 1b. Of 129 enrolled pts, 108 pts were evaluable for response. At 72 wks, sustained virological response (SVR) rate was 40% (range 37-44% across 4 arms). In pts with genotype 1b, SVR rate was 38% (range 25-50% across the 4 arms), and in pts with high viral load, 29% of pts (range 17-43% across 4 arms) achieved a SVR.
Histamine induced mild and transient side effects, including transient flush, headache, hypotension, and tachycardia. Discontinuation rate due to severe adverse events was 5%. Overall, the combination treatment has been well tolerated. Conclusions: The combination of histamine and IFN may increase the efficacy of IFN monotherapy in naïve pts with chronic HCV. |
