Clinical evaluation (Phase I) of a human monoclonal antibody against hepatitis C virus: safety and antiviral activity.
OBJECTIVE
HCV-AB68, a human monoclonal antibody against the envelope protein of hepatitis C virus (HCV), neutralizes HCV in cell-culture and in the HCV-Trimera mouse model. A Phase 1 clinical trial was designed to test safety, tolerability, and antiviral activity of HCV-AB68 in patients with chronic HCV-infection.


RESULTS
Single doses of HCV-AB68, 0.25-40 mg, administered to 15 patients were well tolerated with no moderate or serious adverse events (SAEs) reported. In six patients, HCV-RNA levels transiently decreased by 2- to 100-fold immediately following infusion and rebound to baseline in 24-48 h. Multiple doses of HCV-AB68, 10-120 mg, were administered to 25 patients. Doses were given weekly for 3 weeks, then 3x a week during the fourth week, after which patients were followed for 3 months. No drug-related SAEs were reported and no specific pattern of adverse events was evident. Eight out of 25 patients had at least a 1-log reduction and 17 had at least a 0.75-log reduction in HCV-RNA levels from baseline at one or more time points following HCV-AB68 infusion.


CONCLUSIONS
These data support the investigation of HCV-AB68 in the prevention of recurrent HCV-infection in patients who had received hepatic allografts for end-stage liver disease.
Galun
Eithan
E
Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Terrault
Norah A
NA
Eren
Rachel
R
Zauberman
Arie
A
Nussbaum
Ofer
O
Terkieltaub
Dov
D
Zohar
Meirav
M
Buchnik
Rachel
R
Ackerman
Zvi
Z
Safadi
Rifaat
R
Ashur
Yaffa
Y
Misrachi
Sara
S
Liberman
Yael
Y
Rivkin
Ludmila
L
Dagan
Shlomo
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004361:Drug Tolerance; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000009:adverse effects / Q000627:therapeutic use*; D019698:Hepatitis C, Chronic / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012449:Safety
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D017931:DNA Primers; D018937:Hepatitis C Antibodies; D012367:RNA, Viral