A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (RSV) prophylaxis with motavizumab and palivizumab administered in the same season

Fernandez, Pilar, Trenholme, Adrian, Abarca, Katia, Griffin, M. Pamela, Hultquist, Micki, Harris, Brian, Losonsky, Genevieve, Motavizumab Study Group, McCreanor, J., Nissen, M., Reynolds, G., Robertson, C., Wake, C., Lindemann, C., Mena, P., Novoa, J., Pena, V., Vivanco, G., Austin, N., Brown, J., Jackson, P. and Weston, P. (2010) A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (RSV) prophylaxis with motavizumab and palivizumab administered in the same season. BMC Pediatrics, 10 38.1-38.12. doi:10.1186/1471-2431-10-38


Author Fernandez, Pilar
Trenholme, Adrian
Abarca, Katia
Griffin, M. Pamela
Hultquist, Micki
Harris, Brian
Losonsky, Genevieve
Motavizumab Study Group
McCreanor, J.
Nissen, M.
Reynolds, G.
Robertson, C.
Wake, C.
Lindemann, C.
Mena, P.
Novoa, J.
Pena, V.
Vivanco, G.
Austin, N.
Brown, J.
Jackson, P.
Weston, P.
Title A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (RSV) prophylaxis with motavizumab and palivizumab administered in the same season
Journal name BMC Pediatrics   Check publisher's open access policy
ISSN 1471-2431
Publication date 2010-06-01
Sub-type Article (original research)
DOI 10.1186/1471-2431-10-38
Open Access Status DOI
Volume 10
Start page 38.1
End page 38.12
Total pages 12
Editor Melissa Norton
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Subject C1
920115 Respiratory System and Diseases (incl. Asthma)
060506 Virology
060502 Infectious Agents
920204 Evaluation of Health Outcomes
C Society
Formatted abstract
Background Respiratory syncytial virus (RSV) is an important pathogen causing annual epidemics of bronchiolitis and pneumonia among infants worldwide. High-risk infants currently receive RSV prophylaxis with palivizumab, a humanized RSV monoclonal antibody (MAb). In preclinical in vitro and in vivo (cotton-rat model) studies, motavizumab, a new RSV MAb, was shown to have greater anti-RSV activity than palivizumab. Motavizumab is currently under review for licensing approval. Since both MAbs may be available concurrently, this study evaluated their safety and tolerability when administered sequentially during the same RSV season.

Methods Between April 2006 and May 2006, 260 high-risk infants were randomly assigned 1:1:1 to receive monthly intramuscular injections: 2 doses of motavizumab followed by 3 doses of palivizumab (M/P); 2 doses of palivizumab followed by 3 doses of motavizumab (P/M); or 5 doses of motavizumab (control). Adverse events (AEs, serious AEs [SAEs]), development of antidrug antibody (ADA), and serum drug trough concentrations were assessed.

Results Most children received all 5 doses (246/260 [94.6%]) and completed the study (241/260 [92.7%]). While overall AE rates were similar (mostly level 1 or 2 in severity), SAEs and level 3 AEs occurred more frequently in the M/P group (SAEs: 22.9% M/P, 8.4% P/M, 11.8% motavizumab only; level 3 AEs: 15.7% M/P, 6.0% P/M, 6.5% motavizumab only). This trend in AE rates occurred before and after switching from motavizumab to palivizumab, suggesting a cause other than the combined regimen. Frequencies of AEs judged by the investigator to be related to study drug were similar among groups. Two deaths occurred on study (both in the M/P group, before palivizumab administration); neither was considered by the site investigator to be related to study drug. Mean serum drug trough concentrations were comparable among groups; ADA detection was infrequent (5.1% or less of any group).

Conclusions
The conclusions drawn from this study are limited by the small sample size per group. However, within this small study, overall AE rates, serum drug trough concentrations, and development of ADA associated with administering motavizumab and palivizumab sequentially to high-risk children appear comparable to administering motavizumab alone during the same RSV season. Trial Registration clinicaltrials.gov NCT00316264
Keyword Rsv
Prophylaxis
Bronchiolitis
Pneumonia
Infants
Palivizumab Prophylaxis
Mab
Motovizumab
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Article # 38

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
Clinical Medical Virology Centre Publications
 
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Created: Thu, 12 Aug 2010, 20:31:36 EST by Lesley Arnicar on behalf of Clinical Medical Virology Centre