Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants

A phase 3 randomised double-blind placebo-controlled trial

Katherine L. O'Brien, Aruna Chandran, Robert Weatherholtz, Hasan S. Jafri, M. Pamela Griffin, Terramika Bellamy, Eugene V. Millar, Kathryn M. Jensen, Brian S. Harris, Raymond Reid, Lawrence H. Moulton, Genevieve A. Losonsky, Ruth A. Karron, Mathuram Santosham, Connie Donaldson, Angie Eick-Cost, Mindy Perilla, James Campbell, Daniel VanDeReit, Laura B. Brown & 6 others P. William Gloyd, Michael Seby, Mark A Brown, Delfno Candelaria, Jeffrey L. Foti, Gary Overturf

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children. We aimed to assess the safety and efficacy of an anti-RSV monoclonal antibody (motavizumab) in healthy term (≥36 weeks' gestational age) infants for the prevention of medically attended RSV acute lower respiratory tract infections. Methods: This phase 3, double-blind, placebo-controlled, randomised trial enrolled healthy Native American infants aged 6 months or younger who were born at 36 weeks' gestational age in southwestern USA, on the Navajo Nation, the White Mountain Apache reservation, and the San Carlos Apache Indian reservation. Participants were randomly assigned (2:1) to receive either five monthly intramuscular doses of motavizumab (15 mg/kg) or placebo. They were followed up for 150 days after the first dose, and the primary endpoints were respiratory admission to hospital with a positive result for RSV by RT-PCR and death caused by RSV. Participants were followed up for medically attended wheezing until they reached age 3 years. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00121108. Findings: During the autumn seasons (October to December) between 2004 and 2007, 2127 infants of the 2596 infants enrolled were randomly assigned to receive either motavizumab (1417) or placebo (710). After ITT analysis, motavizumab resulted in an 87% relative reduction (relative risk [RR] 0·13, 95% CI 0·08-0·21) in the proportion of infants admitted to hospital with RSV (21 [2%] of 1417 participants who received motavizumab; 80 [11%] of 710 participants who received placebo, p

Original languageEnglish (US)
Pages (from-to)1398-1408
Number of pages11
JournalThe Lancet Infectious Diseases
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2015

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Respiratory Syncytial Viruses
North American Indians
Virus Diseases
Placebos
Intention to Treat Analysis
Respiratory Tract Infections
Gestational Age
Respiratory Sounds
motavizumab
Randomized Controlled Trials
Monoclonal Antibodies
Safety
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Infectious Diseases

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Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants : A phase 3 randomised double-blind placebo-controlled trial. / O'Brien, Katherine L.; Chandran, Aruna; Weatherholtz, Robert; Jafri, Hasan S.; Griffin, M. Pamela; Bellamy, Terramika; Millar, Eugene V.; Jensen, Kathryn M.; Harris, Brian S.; Reid, Raymond; Moulton, Lawrence H.; Losonsky, Genevieve A.; Karron, Ruth A.; Santosham, Mathuram; Donaldson, Connie; Eick-Cost, Angie; Perilla, Mindy; Campbell, James; VanDeReit, Daniel; Brown, Laura B.; Gloyd, P. William; Seby, Michael; Brown, Mark A; Candelaria, Delfno; Foti, Jeffrey L.; Overturf, Gary.

In: The Lancet Infectious Diseases, Vol. 15, No. 12, 01.12.2015, p. 1398-1408.

Research output: Contribution to journalArticle

O'Brien, KL, Chandran, A, Weatherholtz, R, Jafri, HS, Griffin, MP, Bellamy, T, Millar, EV, Jensen, KM, Harris, BS, Reid, R, Moulton, LH, Losonsky, GA, Karron, RA, Santosham, M, Donaldson, C, Eick-Cost, A, Perilla, M, Campbell, J, VanDeReit, D, Brown, LB, Gloyd, PW, Seby, M, Brown, MA, Candelaria, D, Foti, JL & Overturf, G 2015, 'Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants: A phase 3 randomised double-blind placebo-controlled trial', The Lancet Infectious Diseases, vol. 15, no. 12, pp. 1398-1408. https://doi.org/10.1016/S1473-3099(15)00247-9
O'Brien, Katherine L. ; Chandran, Aruna ; Weatherholtz, Robert ; Jafri, Hasan S. ; Griffin, M. Pamela ; Bellamy, Terramika ; Millar, Eugene V. ; Jensen, Kathryn M. ; Harris, Brian S. ; Reid, Raymond ; Moulton, Lawrence H. ; Losonsky, Genevieve A. ; Karron, Ruth A. ; Santosham, Mathuram ; Donaldson, Connie ; Eick-Cost, Angie ; Perilla, Mindy ; Campbell, James ; VanDeReit, Daniel ; Brown, Laura B. ; Gloyd, P. William ; Seby, Michael ; Brown, Mark A ; Candelaria, Delfno ; Foti, Jeffrey L. ; Overturf, Gary. / Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants : A phase 3 randomised double-blind placebo-controlled trial. In: The Lancet Infectious Diseases. 2015 ; Vol. 15, No. 12. pp. 1398-1408.
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T2 - A phase 3 randomised double-blind placebo-controlled trial

AU - O'Brien, Katherine L.

AU - Chandran, Aruna

AU - Weatherholtz, Robert

AU - Jafri, Hasan S.

AU - Griffin, M. Pamela

AU - Bellamy, Terramika

AU - Millar, Eugene V.

AU - Jensen, Kathryn M.

AU - Harris, Brian S.

AU - Reid, Raymond

AU - Moulton, Lawrence H.

AU - Losonsky, Genevieve A.

AU - Karron, Ruth A.

AU - Santosham, Mathuram

AU - Donaldson, Connie

AU - Eick-Cost, Angie

AU - Perilla, Mindy

AU - Campbell, James

AU - VanDeReit, Daniel

AU - Brown, Laura B.

AU - Gloyd, P. William

AU - Seby, Michael

AU - Brown, Mark A

AU - Candelaria, Delfno

AU - Foti, Jeffrey L.

AU - Overturf, Gary

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N2 - Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children. We aimed to assess the safety and efficacy of an anti-RSV monoclonal antibody (motavizumab) in healthy term (≥36 weeks' gestational age) infants for the prevention of medically attended RSV acute lower respiratory tract infections. Methods: This phase 3, double-blind, placebo-controlled, randomised trial enrolled healthy Native American infants aged 6 months or younger who were born at 36 weeks' gestational age in southwestern USA, on the Navajo Nation, the White Mountain Apache reservation, and the San Carlos Apache Indian reservation. Participants were randomly assigned (2:1) to receive either five monthly intramuscular doses of motavizumab (15 mg/kg) or placebo. They were followed up for 150 days after the first dose, and the primary endpoints were respiratory admission to hospital with a positive result for RSV by RT-PCR and death caused by RSV. Participants were followed up for medically attended wheezing until they reached age 3 years. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00121108. Findings: During the autumn seasons (October to December) between 2004 and 2007, 2127 infants of the 2596 infants enrolled were randomly assigned to receive either motavizumab (1417) or placebo (710). After ITT analysis, motavizumab resulted in an 87% relative reduction (relative risk [RR] 0·13, 95% CI 0·08-0·21) in the proportion of infants admitted to hospital with RSV (21 [2%] of 1417 participants who received motavizumab; 80 [11%] of 710 participants who received placebo, p

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