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OPEN-LABEL PHASE 1B STUDY OF HEPATITIS C VIRAL DYNAMICS WITH OMEGA INTERFERON
TREATMENT
Reported by Jules Levin
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John G McHutchison, Paul J Pockros, Scripps Clinic, La Jolla, CA; Peter
Langecker, Dennis Blanchett, William - Lang, Mark Moran, BioMedicines, Inc,
Emeryville, CA
Background: Omega (w) interferon (IFN) is a type 1 IFN active in vitro
against DNA, RNA and retroviruses. In man w IFN increases IFN response marker
levels. Aims: To evaluate in patients who failed to clear virus with alpha
IFN alone, alpha IFN with ribavirin or pegylated interferon: · hepatitis C
viral dynamics · HCV RNA and ALT response to increasing doses of w · safety,
tolerability, and PK characteristics of w IFN Study design: Three groups of 8
patients (pts) received 15,30 or 60 mg of w IFN sc qd for 14 days. Initially
mean HCV RNA levels were >105 and ALT levels were elevated. HCV RNA levels
were measured at 2,4,7,10,14,19 and 24 hours after initial dosing; 5,10 and
24 hours after dose 2; and every 1-2 days through Day 14. Omega IFN blood
levels were measured at 11 time points for 24 hours following the initial
dose. Results: 16 males and 8 females completed 14 days of daily therapy.
Median half life of elimination of w IFN was approximately 9 hours after a
single 15 mg dose. Six pts required dose reduction and one discontinuation
after 14 days for neutropenia (3/8 at 30 mg, 4/8 at 60 mg). One pt each
discontinued because of pyelonephritis and elevated ALT. Other side effects
were mild to moderate headache (60%), fever (45%) myalgia (45%). Conclusions:
Omega IFN reduces levels of HCV RNA within 48 hours in genotype 1 infected
patients resistant to prior alpha IFN therapy. Further reductions occur in 2
of the 3 groups at 14 days. AE's with w IFN, even with daily dosing, are not
worse than those of other IFNs. Neutropenia may be dose limiting. Prospective
trials are required to further determine the role of Omega IFN for the
treatment of HCV infection.
OPEN-LABEL PHASE II STUDY OF OMEGA INTERFERON IN PREVIOUSLY UNTREATED HCV
INFECTED PATIENTS
Mathias Plauth, Stadisches Klinikum, Dessau Germany; Helga Meisel, Inst fur
Medizinische Virologie, Berlin Germany; Peter Langecker, Mark Moran, William
Lang, Dennis Blanchett, BioMedicines, Emeryville, CA; Jens-Uwe Jetschmann,
Campus Charite, Humboldt Univ, Berlin Germany; Jochen Brack, Klinikum Nord,
Betiebsteil Ochsenzoll, Hamburg Germany; Peter Von Wussow, Privatdozent,
Facharzt fur Innere Medizin, Hannover Germany
Purpose: To measure in naive HCV infected patients - the safety and
tolerability of w interferon (IFN) - the effect of different doses on ALT
levels -the effect of different doses on HCV RNA levels Background: Omega (w)
interferon (IFN) is a type 1 IFN active in vitro against DNA, RNA and
retroviruses. Human administration of w IFN increases IFN response markers.
Study design: Each of three groups of treatment naive HCV infected patients
(pts) received either 15, 30 or 45 m g of w IFN sc daily TIW for 12 weeks.
All pts had HCV RNA levels >105 and elevated ALT levels at study entry. Pts
were evaluated clinically, with hematology, chemistries and HCV RNA assays at
6 time points between day 0 and week 16. HCV RNA assays were also performed
at Days 0,1,2,3,4 and 15. Dose escalation is continuing to 60, 90 and 45 m g
of w IFN sc TIW. Results: Data are presented from 32 patients who have
completed 4 weeks of therapy. Results for HCV RNA and ALT testing are
presented in the table. Adverse events were similar to those seen with other
IFNs. Leukopenia required dose reduction in two pts at the 15 mg dose level
but none at higher doses. No patients discontinued treatment. Conclusions:
Omega IFN is active against type 1 HCV in IFN naive patients. It induced
undetectable HCV RNA levels in 10/30 pts and normalized ALT in 12/32 pts
during the first 28 days of treatment. Omega IFN shows the characteristics of
a clinically useful interferon for the treatment of HCV infection and further
evaluation of higher doses and prolonged treatment is warranted.
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