title: 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.
abstract: 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.
authors.affiliation: University of Texas Health Center, Tyler, TX, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borucki
authors.forename: John
authors.initials: J
authors.lastname: Spritzler
authors.forename: David M
authors.initials: DM
authors.lastname: Asmuth
authors.forename: John
authors.initials: J
authors.lastname: Gnann
authors.forename: Martin S
authors.initials: MS
authors.lastname: Hirsch
authors.forename: Mostafa
authors.initials: M
authors.lastname: Nokta
authors.forename: Francesca
authors.initials: F
authors.lastname: Aweeka
authors.forename: Paul I
authors.initials: PI
authors.lastname: Nadler
authors.forename: Fred
authors.initials: F
authors.lastname: Sattler
authors.forename: Beverly
authors.initials: B
authors.lastname: Alston
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Nevin
authors.forename: Susan
authors.initials: S
authors.lastname: Owens
authors.forename: Karen
authors.initials: K
authors.lastname: Waterman
authors.forename: Larry
authors.initials: L
authors.lastname: Hubbard
authors.forename: Angela
authors.initials: A
authors.lastname: Caliendo
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
mesh_terms: 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*
chemical_list: 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