Motavizumab for Prophylaxis of Respiratory Syncytial Virus in High-Risk Children: A Noninferiority Trial

被引：159

作者：

Carbonell-Estrany, Xavier ^{[1
]}

Simoes, Eric A. F. ^{[2
,3
]}

Dagan, Ron ^{[4
,5
]}

Hall, Caroline B. ^{[6
,7
]}

Harris, Brian ^{[8
]}

Hultquist, Micki ^{[8
]}

Connor, Edward M. ^{[8
]}

Losonsky, Genevieve A. ^{[8
]}

机构：

[1] Hosp St Joan de Deu, Hosp Clin, Serv Neonatol, Agrupacio Saniteria Clin, Barcelona 08028, Spain

[2] Univ Colorado, Sch Med, Dept Pediat, Denver, CO USA

[3] Childrens Hosp, Div Infect Dis, Denver, CO 80218 USA

[4] Soroka Univ, Med Ctr, Pediat Infect Dis Unit, Beer Sheva, Israel

[5] Ben Gurion Univ Negev, Fac Hlth Sci, Beer Sheva, Israel

[6] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA

[7] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA

[8] Medimmune Inc, Gaithersburg, MD 20878 USA

来源：

PEDIATRICS | 2010年 / 125卷 / 01期

关键词：

clinical trial; motavizumab; palivizumab; pediatric; respiratory infection; respiratory syncytial virus; HUMANIZED MONOCLONAL-ANTIBODY; PALIVIZUMAB PROPHYLAXIS; PREMATURE-INFANTS; SAFETY; PHARMACOKINETICS; RSV; PREVENTION; INFECTION; TOLERANCE; DISEASE;

D O I：

10.1542/peds.2008-1036

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

OBJECTIVE: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by similar to 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab. METHODS: This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged <= 6 months at enrollment or children aged <= 24 months with chronic lung disease of prematurity who received 15 mg/kg palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations. RESULTS: Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events. CONCLUSIONS: Children receiving prophylaxis with motavizumab or palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk. Pediatrics 2010; 125: e35-e51

引用

页码：E35 / E51

页数：17

共 22 条

[1] Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Motavizumab, a Humanized, Enhanced-Potency Monoclonal Antibody for the Prevention of Respiratory Syncytial Virus Infection in At-Risk Children [J].