A pilot trial of recombinant interleukin-12 in patients with chronic hepatitis C who previously failed treatment with interferon-α

• Published in: The American journal of gastroenterology Vol. 96; no. 8; pp. 2473 - 2479
• Main Authors: O’Brien, Christopher B, Moonka, Dilip K, Henzel, Barbara S, Caufield, Maureen, DeBruin, Michael F
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Inc 01.08.2001; Blackwell Publishing
• Subjects: Adjuvants, Immunologic - therapeutic use; Analysis of Variance; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - therapeutic use; Biological and medical sciences; Cytokines - blood; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis C, Chronic - drug therapy; Humans; Interferon-alpha - therapeutic use; Interleukin-12 - therapeutic use; Liver Function Tests; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pilot Projects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral - blood; Treatment Failure; Treatment Outcome; Human; Toxicity; Treatment efficiency; Cytokine; Hepatic disease; Interleukin 12; Infection; Chemotherapy; Treatment; Immunotherapy; Viral disease; Antiviral; Digestive diseases; Dose; Comparative study; Viral hepatitis C
• ISSN: 0002-9270; 1572-0241
• DOI: 10.1016/S0002-9270(01)02520-5

OBJECTIVE: Interleukin-12 is a cytokine with a multitude of immunomodulatory actions. Currently, interferon-α (IFN-α) 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-α 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.