Animal Models
Woodchuck Hepatitis
Woodchuck hepatitis virus (WHV) is closely related to the human
hepatitis B virus (HBV), and WHV infection in woodchucks is
an animal model for chronic HBV infection in humans. Data are
available on effects of Zadaxin from three completed studies
with this experimental model.
| Study
1 (62) |
| • |
6 WHV chronically
infected animals received Zadaxin (10 µg/kg)
BIW for 30 weeks |
| • |
6 age- and sex-matched
infected animals were used as untreated controls |
| End-of-treatment
results: |
| • |
Serum WHV DNA
levels fell by 99% in all Zadaxin-treated animals |
| • |
No changes
were observed in serum WHV DNA in the 6 untreated controls |
| The effect was transient,
however, and serum WHV DNA returned to pretreatment levels
in the follow-up period. |
| Study
2 (63) |
| • |
24 WHV chronically
infected animals received Zadaxin (900 µg/m2,
23 µg/kg, or
10 µg/kg) BIW
for 30 weeks |
| • |
12 age- and sex-matched
infected animals were used as controls |
| End-of-treatment
results: |
| • |
Serum WHV
DNA levels fell by 99% to 99.9% in all Zadaxin-treated
groups |
| • |
No changes
were observed in serum WHV DNA in control animals |
Figure 3 shows,
by logarithmic scale, mean serum levels of WHV DNA for
the Zadaxin (10 µg/kg)
and placebo-
treated animals. These results are similar to those obtained
with IFNα. (64) |
 |
Figure 3.
Serum woodchuck hepatitis virus (WHV) DNA in Zadaxin-treated
and placebo-treated animals. Zadaxin was given biweekly
for 24 weeks, with 12 weeks follow-up. Zadaxin treatment
period is indicated by a solid line at the top of the
figure. The figure shows that 6 months of treatment with
Zadaxin significantly decreases serum WHV DNA compared
with placebo-treated animals. (63) |
| Study
3 (65) |
| • |
20 WHV chronically
infected animals received Zadaxin (900 µg/m2)
BIW for 3 years |
| • |
20 age- and sex-matched
infected animals were used as placebo controls |
| End-of-treatment
results: |
| • |
Serum WHV DNA
in treated animals was significantly less than in placebo-treated
animals 1 month after
beginning treatment (P < 0.001) |
| • |
Serum WHV DNA
level remained significantly lower than placebo controls
throughout the remainder of the 152-week treatment |
| • |
After 48 weeks, 2 placebo
animals died of hepatocellular carcinoma (HCC), while
there were no deaths in the Zadaxin-treated animals |
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