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

Michael J. Borucki, John Spritzler, David Asmuth, John Gnann, Martin S. Hirsch, Mostafa Nokta, Francesca Aweeka, Paul I. Nadler, Fred Sattler, Beverly Alston, Thomas T. Nevin, Susan Owens, Karen Waterman, Larry Hubbard, Angela Caliendo, Richard B Pollard

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 15 mg 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.

Original languageEnglish (US)
Pages (from-to)103-111
Number of pages9
JournalAntiviral Research
Volume64
Issue number2
DOIs
StatePublished - Nov 2004

Fingerprint

Cytomegalovirus Retinitis
Cytomegalovirus
Anti-Idiotypic Antibodies
Acquired Immunodeficiency Syndrome
Monoclonal Antibodies
Placebos
Therapeutics
Disease Progression
Retinitis
sevirumab
Antiviral Agents
Reading
Research Personnel
Survival
Mortality

Keywords

  • AIDS
  • Cytomegalovirus
  • Cytomegalovirus retinitis
  • Monoclonal antibody
  • MSL-109

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

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. / Borucki, Michael J.; Spritzler, John; Asmuth, David; Gnann, John; Hirsch, Martin S.; Nokta, Mostafa; Aweeka, Francesca; Nadler, Paul I.; Sattler, Fred; Alston, Beverly; Nevin, Thomas T.; Owens, Susan; Waterman, Karen; Hubbard, Larry; Caliendo, Angela; Pollard, Richard B.

In: Antiviral Research, Vol. 64, No. 2, 11.2004, p. 103-111.

Research output: Contribution to journalArticle

Borucki, Michael J. ; Spritzler, John ; Asmuth, David ; Gnann, John ; Hirsch, Martin S. ; Nokta, Mostafa ; Aweeka, Francesca ; Nadler, Paul I. ; Sattler, Fred ; Alston, Beverly ; Nevin, Thomas T. ; Owens, Susan ; Waterman, Karen ; Hubbard, Larry ; Caliendo, Angela ; Pollard, Richard B. / 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. In: Antiviral Research. 2004 ; Vol. 64, No. 2. pp. 103-111.
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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 15 mg 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.",
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AU - Borucki, Michael J.

AU - Spritzler, John

AU - Asmuth, David

AU - Gnann, John

AU - Hirsch, Martin S.

AU - Nokta, Mostafa

AU - Aweeka, Francesca

AU - Nadler, Paul I.

AU - Sattler, Fred

AU - Alston, Beverly

AU - Nevin, Thomas T.

AU - Owens, Susan

AU - Waterman, Karen

AU - Hubbard, Larry

AU - Caliendo, Angela

AU - Pollard, Richard B

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N2 - 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 15 mg 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.

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