Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study.
Previous clinical trials have suggested that thymosin alpha1 (Talpha1), an immunomodulatory peptide, may be effective in the treatment of chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of Talpha1 in a multicentre, placebo-controlled and double-blind study of 97 patients with serum hepatitis B virus (HBV) DNA- and hepatitis B e antigen (HBeAg)-positive CHB. Patients who had been hepatitis B surface antigen (HBsAg) positive for at least 12 months entered a 3-month screening period prior to randomization. Forty-nine patients received Talpha1 (1.6 mg) and 48 patients received placebo, twice weekly for 6 months, and were followed-up for an additional 6 months. At inclusion, both groups were comparable for age, gender, histological grading, and aminotransferase and HBV DNA levels. A complete response to treatment, defined as a sustained serum HBV DNA-negative status (two negative results at least 3 months apart) during the 12-month study, with negative HBV DNA and HBeAg values at month 12, was seen in seven (14%) patients given Talpha1 and in two (4%) patients treated with placebo (P = 0.084). Five (10%) patients given Talpha1 and four (8%) patients given placebo exhibited a delayed response (defined as sustained serum HBV DNA negativity achieved after the 12-month study period with negative HBV DNA and HBeAg values at the last assessment). A total of 12 (25%) patients given Talpha1 and six (13%) patients given placebo showed a sustained loss of HBV DNA with a negative HBeAg value during or following the 12-month study period (P < 0.11). These results do not confirm observations of treatment efficacy reported in other clinical studies.
Mutchnick
M G
MG
Division of Gastroenterology, Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Lindsay
K L
KL
Schiff
E R
ER
Cummings
G D
GD
Appelman
H D
HD
Peleman
R R
RR
Silva
M
M
Roach
K C
KC
Simmons
F
F
Milstein
S
S
Gordon
S C
SC
Ehrinpreis
M N
MN
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000302:isolation & purification / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D013947:Thymosin; D000077596:Thymalfasin