A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis B
Identifieur interne : 00BF17 ( Main/Exploration ); précédent : 00BF16; suivant : 00BF18A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis B
Auteurs : Vicente Carre O [Espagne] ; Stefan Zeuzem [Allemagne] ; Uwe Hopf [Allemagne] ; Patrick Marcellin [France] ; W. Graham E. Cooksley [Australie] ; Johan Fevery [Belgique] ; Moisés Diago [Espagne] ; Rajender Reddy [États-Unis] ; Marion Peters [États-Unis] ; Karen Rittweger [États-Unis] ; Ashok Rakhit [États-Unis] ; Margarita Pardo [Espagne]Source :
- Journal of Hepatology [ 0168-8278 ] ; 2000.
English descriptors
- KwdEn :
- Adverse event, Adverse events, Baseline, Baseline level, Biologic activity, Carrefio, Chronic, Chronic hepatitis, Clin cancer, Consecutive weeks, Detection limit, Dos, Dose group, Dose levels, Dosing, Drug dose, Fundacion jimenez diaz, Hbeag, Hepatitis, Higher dose, Human interleukin, Immune system, Injection site, Interferon, Interferon alfa, Liver center, Liver disease, Liver diseases, Local reaction, Lymphocyte, Maximum increase, Miami school, Moderate decreases, Neutrophil counts, Normal range, Pharmacodynamic profile, Phase study, Pilot study, Royal brisbane hospital, Serum levels, Serum samples, Significant differences, Statistical analysis, Upper limit, Viral, Viral hepat, Virus infection, Virus load, Virus replication, Worst value.
- Teeft :
- Adverse event, Adverse events, Baseline, Baseline level, Biologic activity, Carrefio, Chronic, Chronic hepatitis, Clin cancer, Consecutive weeks, Detection limit, Dos, Dose group, Dose levels, Dosing, Drug dose, Fundacion jimenez diaz, Hbeag, Hepatitis, Higher dose, Human interleukin, Immune system, Injection site, Interferon, Interferon alfa, Liver center, Liver disease, Liver diseases, Local reaction, Lymphocyte, Maximum increase, Miami school, Moderate decreases, Neutrophil counts, Normal range, Pharmacodynamic profile, Phase study, Pilot study, Royal brisbane hospital, Serum levels, Serum samples, Significant differences, Statistical analysis, Upper limit, Viral, Viral hepat, Virus infection, Virus load, Virus replication, Worst value.
Abstract
Abstract: Background/Aims: Interleukin-12 (IL-12) may be active against hepatitis B virus (HBV). The objective of the study was to assess the tolerability, activity, pharmacokinetics, and pharmacodynamics of three dose levels (0.03 μg/kg b.w., n=15; 0.25 μg/kg b.w., n=15; 0.50 μg/kg b.w., n=16) of recombinant human (rHu) IL-12 given s.c. once a week for 12 consecutive weeks. Methods: Forty-six patients with chronic hepatitis B, HBV DNA positivity and aminotransferase elevation were included in a multicenter prospective randomized phase I/II study. Results: Compared with the baseline, HBV DNA levels had decreased significantly at the end of rHuIL-12 treatment and after the 12-week follow-up period (p<0.001). The response to rHuIL-12 treatment was dose-dependent: at the end of the study HBV DNA clearance was greater in patients treated with 0.50 μg/kg b.w. (25%) or with 0.25 μg/kg b.w. (13%) compared with those given 0.03 μg/kg b.w. (7%). Moreover, HBeAg became undetectable at the end of follow-up in five of the patients given the 0.25 μg/kg (2/15) or the 0.50 μg/kg (3/16) dose. The drug pharmacology showed that IL-12 had an estimated half-life of 30 h with levels remaining detectable for more than 48 h after rHuIL-12 administration. The serum levels of IL-12, interferon-γ, IL-10, neopterin and β2-microglobulin as well as the area under the curve (AUC) were rHuIL-12 dose-related. Side effects were observed more frequently with higher doses, including moderate decreases in lymphocyte and neutrophil counts; three patients withdrew prematurely from treatment. The local reaction observed at the injection site was unrelated to the drug dose. Only one patient showed detectable antibody levels to rHuIL-12 without clinical impact. Conclusions: Treatment with rHuIL-12 at the doses investigated is safe and tolerable, and appears to be active against HBV in patients with chronic hepatitis B.
Url:
DOI: 10.1016/S0168-8278(00)80078-1
Affiliations:
- Allemagne, Australie, Belgique, Espagne, France, États-Unis
- Berlin, Californie, Communauté de Madrid, District de Darmstadt, Floride, Hesse (Land), New Jersey
- Berlin, Francfort-sur-le-Main, Madrid
Links toward previous steps (curation, corpus...)
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Le document en format XML
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<term>Baseline</term>
<term>Baseline level</term>
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<term>Carrefio</term>
<term>Chronic</term>
<term>Chronic hepatitis</term>
<term>Clin cancer</term>
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<term>Dose levels</term>
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<term>Human interleukin</term>
<term>Immune system</term>
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<term>Interferon alfa</term>
<term>Liver center</term>
<term>Liver disease</term>
<term>Liver diseases</term>
<term>Local reaction</term>
<term>Lymphocyte</term>
<term>Maximum increase</term>
<term>Miami school</term>
<term>Moderate decreases</term>
<term>Neutrophil counts</term>
<term>Normal range</term>
<term>Pharmacodynamic profile</term>
<term>Phase study</term>
<term>Pilot study</term>
<term>Royal brisbane hospital</term>
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<term>Serum samples</term>
<term>Significant differences</term>
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<term>Chronic hepatitis</term>
<term>Clin cancer</term>
<term>Consecutive weeks</term>
<term>Detection limit</term>
<term>Dos</term>
<term>Dose group</term>
<term>Dose levels</term>
<term>Dosing</term>
<term>Drug dose</term>
<term>Fundacion jimenez diaz</term>
<term>Hbeag</term>
<term>Hepatitis</term>
<term>Higher dose</term>
<term>Human interleukin</term>
<term>Immune system</term>
<term>Injection site</term>
<term>Interferon</term>
<term>Interferon alfa</term>
<term>Liver center</term>
<term>Liver disease</term>
<term>Liver diseases</term>
<term>Local reaction</term>
<term>Lymphocyte</term>
<term>Maximum increase</term>
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<term>Moderate decreases</term>
<term>Neutrophil counts</term>
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<term>Pharmacodynamic profile</term>
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<term>Serum samples</term>
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<front><div type="abstract" xml:lang="en">Abstract: Background/Aims: Interleukin-12 (IL-12) may be active against hepatitis B virus (HBV). The objective of the study was to assess the tolerability, activity, pharmacokinetics, and pharmacodynamics of three dose levels (0.03 μg/kg b.w., n=15; 0.25 μg/kg b.w., n=15; 0.50 μg/kg b.w., n=16) of recombinant human (rHu) IL-12 given s.c. once a week for 12 consecutive weeks. Methods: Forty-six patients with chronic hepatitis B, HBV DNA positivity and aminotransferase elevation were included in a multicenter prospective randomized phase I/II study. Results: Compared with the baseline, HBV DNA levels had decreased significantly at the end of rHuIL-12 treatment and after the 12-week follow-up period (p<0.001). The response to rHuIL-12 treatment was dose-dependent: at the end of the study HBV DNA clearance was greater in patients treated with 0.50 μg/kg b.w. (25%) or with 0.25 μg/kg b.w. (13%) compared with those given 0.03 μg/kg b.w. (7%). Moreover, HBeAg became undetectable at the end of follow-up in five of the patients given the 0.25 μg/kg (2/15) or the 0.50 μg/kg (3/16) dose. The drug pharmacology showed that IL-12 had an estimated half-life of 30 h with levels remaining detectable for more than 48 h after rHuIL-12 administration. The serum levels of IL-12, interferon-γ, IL-10, neopterin and β2-microglobulin as well as the area under the curve (AUC) were rHuIL-12 dose-related. Side effects were observed more frequently with higher doses, including moderate decreases in lymphocyte and neutrophil counts; three patients withdrew prematurely from treatment. The local reaction observed at the injection site was unrelated to the drug dose. Only one patient showed detectable antibody levels to rHuIL-12 without clinical impact. Conclusions: Treatment with rHuIL-12 at the doses investigated is safe and tolerable, and appears to be active against HBV in patients with chronic hepatitis B.</div>
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