A pilot trial of recombinant interleukin-12 in patients with chronic hepatitis C who previously failed treatment with interferon-alpha.
OBJECTIVE
Interleukin-12 is a cytokine with a multitude of immunomodulatory actions. Currently, interferon-alpha (IFN-alpha) monotherapy and combination treatment with IFN and ribavirin are the only therapies with proven efficacy against chronic hepatitis C infection. The purpose of this study was to assess the safety and antiviral activity of recombinant interleukin-12 (rhIL-12) in adults with chronic hepatitis C who did not achieve a sustained response to previous IFN-alpha therapy.


METHODS
This was a randomized, placebo-controlled, double-blind trial. We randomized 24 patients to one of three dose groups: 30 ng/kg, 100 ng/kg, and 300 ng/kg. Within each group, six patients received rhIL-12, and two patients received placebo administered s.c. twice a week for 12 wk.


RESULTS
Three of six patients treated with rhIL-12 at a dose of 300 ng/kg had loss of detectable hepatitis C RNA by reverse transcription-polymerase chain reaction compared with the placebo group (p = 0.05). All patients relapsed at the end of the 3-month treatment period. No other dose group demonstrated a loss of detectable hepatitis C RNA.


CONCLUSIONS
RhIL-12 at 300 ng/kg can suppress hepatitis C RNA to undetectable levels by reverse transcription-polymerase chain reaction, although relapse occurred when treatment was stopped. RhIL-12 was well tolerated with the most common side effects being flu-like symptoms and headaches.
O'Brien
C B
CB
Department of Medicine, University of Pennsylvania, Philadelphia, USA.
Moonka
D K
DK
Henzel
B S
BS
Caufield
M
M
DeBruin
M F
MF
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D018664:Interleukin-12 / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017211:Treatment Failure; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha; D012367:RNA, Viral; D018664:Interleukin-12