Albinterferon Alfa-2b Was Not Inferior to Pegylated Interferon-α in a Randomized Trial of Patients With Chronic Hepatitis C Virus Genotype 1

Zeuzem, Stefan; Sulkowski, Mark S.; Lawitz, Eric; Rustgi, Vinod K.; Rodrı́guez-Torres, Maribel; Bacon, Bruce R.; Grigorescu, Mircea; Tice, Alan D.; Lurie, Yoav; Cianciara, J; Muir, Andrew J.; Cronin, Patrick W.; Pulkstenis, Erik; Subramanian, G. Mani; McHutchison, John G.

doi:10.1053/j.gastro.2010.06.066

Cited by 65 publications

(47 citation statements)

References 22 publications

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“…The efficacy of alb-IFN was evaluated in clinical phase IIb studies with IFN-naive patients chronically infected with HCV, in which it was administered every 2 or 4 weeks (Zeuzem et al, 2008). The clinical studies showed that alb-IFN had similar anti-viral effects to pegIFN-a (Nelson et al, 2010;Zeuzem et al, 2010). However, in phase III studies, a higher incidence of serious pulmonary adverse events was observed in alb-IFN-treated patients, which resulted in the cessation of further development by Novartis and Human Genome Sciences in 2010.…”

Section: New Ifnsmentioning

confidence: 99%

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Gibbert

Schlaak

Yang

et al. 2013

British J Pharmacology

152

138

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During most viral infections, the immediate host response is characterized by an induction of type I IFN. These cytokines have various biological activities, including anti‐viral, anti‐proliferative and immunomodulatory effects. After induction, they bind to their IFN‐α/β receptor, which leads to downstream signalling resulting in the expression of numerous different IFN‐stimulated genes. These genes encode anti‐viral proteins that directly inhibit viral replication as well as modulate immune function. Thus, the induction of type I IFN is a very powerful tool for the host to fight virus infections. Many viruses evade this response by various strategies like the direct suppression of IFN induction or inhibition of the IFN signalling pathway. Therefore, the therapeutic application of exogenous type I IFN or molecules that induce strong IFN responses should be of great potential for future immunotherapies against viral infections. Type I IFN is currently used as a treatment in chronic hepatitis B and C virus infection, but as yet is not widely utilized for other viral infections. One reason for this restricted clinical use is that type I IFN belongs to a multigene family that includes 13 different IFN‐α subtypes and IFN‐β, whose individual anti‐viral and immunomodulatory properties have so far not been investigated in detail to improve IFN therapy against viral infections in humans. In this review, we summarize the recent achievements in defining the distinct biological functions of type I IFN subtypes in cell culture and in animal models of viral infection as well as their clinical usage in chronic hepatitis virus infections.

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Section: New Ifnsmentioning

confidence: 99%

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Gibbert

Schlaak

Yang

et al. 2013

British J Pharmacology

152

138

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“…14 Moreover, recombinant albumin has been successfully fused to several therapeutic proteins, including insulin, hirudin, and interferon. [15][16][17] Thus, the albumin fusion technology for extending the half-life of FIX takes advantage of the biologic characteristics of albumin while at the same time allows physiologic function of an unchanged wild-type FIX.…”

Section: Introductionmentioning

confidence: 99%

Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients

Santagostino

Négrier

Klamroth

et al. 2012

Blood

164

165

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“…Bone marrow suppression is a known effect of all interferons, with effects on neutrophil count occurring earlier than effects on hemoglobin or platelets. The 900-g dose used as a single dose in this trial, when given every 2 weeks with ribavirin on the basis of the subject's weight, was not different from pegylated interferon alfa-2a in inducing neutropenia (8). There was a modest decline in the hemoglobin concentration (ϳ0.6 to 0.7 g/liter) over the study in both groups, consistent with the blood-drawing requirements (130 ml) of the study, although an effect from albIFN cannot be ruled out.…”

Section: Discussionmentioning

confidence: 90%

“…Samples were collected for pharmacokinetic analysis predosing and at 3 (48 h) 5 (96 h), 8,15,22,29,36, and 43 days postdosing. The following pharmacokinetic parameters were determined using noncompartmental method(s): the area under the concentration time-curve (AUC) from time zero to time t (AUC 0-t ), the area under the concentration-time curve from time zero to infinity (AUC 0-ϱ ), the maximum concentration in plasma (C max ), the time to C max (T max ), t 1/2 , and clearance (CL/F).…”

Section: Methodsmentioning

confidence: 99%

“…For pegylated interferon alfa-2a, a modest 25% to 45% higher level of exposure is seen in subjects undergoing hemodialysis (4). The present study evaluated a dose of 900 g albinterferon, as it was the lower of the bimonthly doses evaluated in phase 3 studies and allowed an adequate safety margin in the event of an unexpected increase in the level of exposure to albIFN in subjects with ESRD (8).…”

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confidence: 99%

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Single-Dose Pharmacokinetics, Safety, and Tolerability of Albinterferon Alfa-2b in Subjects with End-Stage Renal Disease on Hemodialysis Compared to Those in Matched Healthy Volunteers

Serra

Sun

Karwowska

et al. 2011

Antimicrob Agents Chemother

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Albinterferon alfa-2b (albIFN) is being developed, in combination with ribavirin, for the treatment of hepatitis C virus infection. This study was designed to evaluate the pharmacokinetics, safety, and tolerability of a 900-g dose of albIFN administered as a single subcutaneous injection in end-stage renal disease (ESRD) patients on hemodialysis and matched healthy volunteers (by age [؎5 years], weight [؎5 kg], and gender). The maximum concentration in plasma (C max ) and the area under the concentration-time curve from time zero to infinity (AUC 0-ؕ ) were 42.8 ؎ 14.0 ng/ml and 16,414 ؎ 4,203 ng ⅐ h/ml, respectively, for healthy volunteers, while the C max and AUC 0-ؕ were 49.9 ؎ 20.9 ng/ml and 18,919 ؎ 8,008 ng ⅐ h/ml, respectively, for ESRD patients. The geometric least-squares mean ratios were 1.15 (90% confidence interval [CI], 0.78, 1.68) for C max and 1.11 (90% CI, 0.83, 1.48) for AUC 0-ؕ . Adverse events were as expected for an interferon (e.g., flu-like symptoms), with the main laboratory adverse event being a decline in total white blood cell count, which was specifically related to a decline in the neutrophil count. This effect was somewhat greater in the ESRD patients, with the maximal decreases in neutrophil counts from those at the baseline being (؊2.6 ؎ 0.32) ؋ 10 9 and (؊2.19 ؎ 0.58) ؋ 10 9 cells/liter for the ESRD patients and the healthy volunteers, respectively. This study indicates no significant effect of renal failure on the pharmacokinetics of albIFN. Safety and tolerability were as expected for an interferon.

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Albinterferon Alfa-2b Was Not Inferior to Pegylated Interferon-α in a Randomized Trial of Patients With Chronic Hepatitis C Virus Genotype 1

Abstract: albIFN 900 μg every 2 weeks showed comparable efficacy, with similar serious/severe AE rates, although with a higher discontinuation rate, vs Peg-IFNα-2a in patients with chronic HCV genotype 1.

Cited by 65 publications

References 22 publications

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients

Single-Dose Pharmacokinetics, Safety, and Tolerability of Albinterferon Alfa-2b in Subjects with End-Stage Renal Disease on Hemodialysis Compared to Those in Matched Healthy Volunteers

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