A phase II, double-masked, randomized, placebo-controlled evaluation of a human monoclonal anti-Cytomegalovirus antibody (MSL-109) in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with Cytomegalovirus retinitis.
ACTG 266 was designed as a randomized study to evaluate two doses of the human monoclonal antibody directed against CMV gH (MSL-109) versus placebo, each in combination with standard antiviral therapy for the treatment of newly diagnosed Cytomegalovirus (CMV) retinitis in AIDS patients. A total of 82 subjects were enrolled and received either placebo (n = 28), or MSL-109 at 15 mg (n = 26) or 60 mg (n = 28) every 2 weeks until disease progression was diagnosed. The primary endpoint, disease progression, was determined by masked reading of retinal photographs taken every 4 weeks read by a single investigator. The median time to progression was 8.0, 8.3, and 12.1 weeks in the placebo, MSL-109 15mg and MSL-109 60 mg cohorts, respectively (P = 0.087, placebo versus 60 mg cohort). There were 22 deaths during the study period (9, 9, and 4 in the placebo, MSL-109 15 mg and MSL-109 60 mg cohorts, respectively (P = 0.0058, placebo versus 60 mg cohort)). MSL-109 was well tolerated with no significant adverse events attributable to study medication. The unexplained survival advantage in the higher dose cohort was discordant with the findings of the parallel Studies of Ocular Complications of AIDS Research Group (SOCA)-Monoclonal Anti-CMV Retinitis Trial (MACRT), which was prematurely halted because of increased mortality in subjects treated with high-dose MSL-109, recognizing that A266 enrolled subjects with newly diagnosed, whereas the MACRT enrolled subjects with relapsed, CMV retinitis.
Borucki
Michael J
MJ
University of Texas Health Center, Tyler, TX, USA.
Spritzler
John
J
Asmuth
David M
DM
Gnann
John
J
Hirsch
Martin S
MS
Nokta
Mostafa
M
Aweeka
Francesca
F
Nadler
Paul I
PI
Sattler
Fred
F
Alston
Beverly
B
Nevin
Thomas T
TT
Owens
Susan
S
Waterman
Karen
K
Hubbard
Larry
L
Caliendo
Angela
A
Pollard
Richard B
RB
D017088:AIDS-Related Opportunistic Infections / Q000401:mortality / Q000628:therapy* / Q000821:virology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects; D017726:Cytomegalovirus Retinitis / Q000401:mortality / Q000628:therapy* / Q000821:virology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D017245:Foscarnet / Q000008:administration & dosage / Q000627:therapeutic use; D015774:Ganciclovir / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C409204:sevirumab; D017245:Foscarnet; D015774:Ganciclovir