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C1. Clinical trials (abstracts submitted to C1 should choose a secondary category that describes the subject matter of the trial)
Oral Abstract Submission
Mary Pamela Griffin, MD
Senior Director
AstraZeneca
Gaithersburg, MD
Disclosure: AstraZeneca: Employee, Shareholder
Yuan Yuan, PhD
Principal Statistician
AstraZeneca
Gaithersburg, MD
Disclosure: AstraZeneca: Employee, Shareholder
Therese Takas, BS
Director, Clinical Operations
AstraZeneca
Gaithersburg, MD
Disclosure: AstraZeneca: Employee, Shareholder
John DeVincenzo, MD
Professor
University of Tennessee School of Medicine
Memphis, Tennessee
Disclosure: MedImmune/Astrazeneca: Consultant, Grant/Research Support, Scientific Research Study Investigator, Speaker's Bureau
Joseph B. Domachowske, MD
Dr.
SUNY Upstate Medical University
Syracuse, NY
Disclosure: AstraZeneca: Scientific Research Study Investigator
Eric A. Simoes, MBBS, DCH, MD
Professor of Pediatrics
University of Colorado
Denver, CO
Disclosure: Astra Zeneca: Consultant, Scientific Research Study Investigator, Research Grant or Support
Anis Khan, PhD
Principal Clinical Pharmacokineticist
AstraZeneca
Gaithersburg, MD
Disclosure: AstraZeneca: Employee, Shareholder
Mark T. Esser, Ph.D.
Sr. Director
AstraZeneca
Gaithersburg, MD
Disclosure: AstraZeneca: Employee, Shareholder
Filip Dubovsky, MD, MPH
Vice-President
AstraZeneca
Gaithersburg, MD
Disclosure: AstraZeneca: Employee, Shareholder
Tonya L. Villafana, PhD MPH
Product Development Team Leader
AstraZeneca
Gaithersburg, MD
Disclosure: AstraZeneca: Employee, Shareholder
Background : RSV is the principal cause of lower respiratory tract infection (LRTI) among infants, and a significant unmet need exists for RSV prevention in healthy infants. We have developed a highly-potent, extended half-life monoclonal antibody (mAb), to protect infants for an entire RSV season using a single IM dose. Here we report the efficacy, safety, pharmacokinetics, and anti-drug antibody (ADA) responses for MEDI8897 in palivizumab-ineligible preterm infants born between 29 and 35 weeks gestation.
Methods : 1453 Infants were randomized 2:1 to receive a single 50 mg IM injection of MEDI8897 (n=969) or placebo (n=484) and followed for 360 days. Enrollment occurred just prior to the 2016 and 2017 RSV seasons in 23 northern and southern hemisphere countries. Blood was collected periodically. Infants with a medically-attended (MA) LRTI (outpatient or inpatient) had nasal swabs obtained for central RSV testing by RT-PCR. Predefined clinical criteria were used for the case definition.
Results : 1417 (97.5%) subjects completed the 150-day efficacy follow-up period and 1367 (94.1%) completed the study. In the MEDI8897 group, a 70.1% (95% CI: 52.3%, 81.2%; p<0.0001) reduction in the incidence of medically attended RSV LRTI and a 78.4% (95% CI: 51.9%, 90.3%; p=0.0002) reduction in the incidence of RSV LRTI hospitalization was achieved. These efficacy results were consistent when analyzed by hemisphere, RSV subtype, and subject demographics. Similar proportions of adverse events (86.8% placebo; 86.2% MEDI8897) and serious adverse events (16.9% placebo; 11.2% MEDI8897) were reported in study subjects. There were no significant hypersensitivity reactions with similar proportions reported for both groups (0.6% placebo; 0.5% MEDI8897). The incidence of ADA detected any time post baseline was low (3.8% placebo; 5.6% MEDI8897) with no impact on PK or safety. The occurrence of non-RSV LRTIs was similar for both groups indicating no replacement by other pathogens.
Conclusion :
In this large randomized study of RSV prophylaxis in healthy preterm infants, MEDI8897 immunoprophylaxis provided a significant reduction in RSV MA-LRTI and hospitalization. These results have promising implications for the future of RSV prophylaxis for all infants.
This study was funded by AstraZeneca and Sanofi Pasteur.