A Phase 1b/2a Randomized, Double-Blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI8897, a Monoclonal Antibody With an Extended Half-life Against Respiratory Syncytial Virus, in Healthy Preterm Infants

Phase 1

Completed

Conditions: Respiratory Syncytial Virus

Interventions: Drug: MEDI8897 10 mg
Drug: Placebo
Drug: MEDI8897 25 mg
Drug: MEDI8897 50 mg

Registration Number: NCT02290340

Lead Sponsor: MedImmune LLC

Brief Summary: The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of an extended half-life anti-respiratory syncytial virus (RSV) monoclonal antibody compared to placebo when administered to healthy preterm infants.

Detailed Description: This Phase 1b/2a study will be a dose-escalation design to begin data collection on PK and safety in children. The population to be enrolled is healthy preterm infants born between 32 weeks 0 days and 34 weeks 6 days gestation who would not receive RSV prophylaxis based on the American Academy of Pediatrics (AAP) or other local guidelines. These subjects will not be receiving palivizumab, allowing for a placebo comparator group to begin collecting data on incidence rates of RSV medically attended lower respiratory illness (MA-LRI) and efficacy. Enrollment is planned at approximately 20 sites in the USA, Chile, and South Africa.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 151

Inclusion Criteria

Healthy infants born between 32 weeks 0 days and 34 weeks 6 days gestational age
Infants who are entering their first RSV season at the time of screening

Key

Exclusion Criteria

Gestational age < 32 weeks 0 days and >34 weeks 6 days
Meets AAP or other local criteria to receive commercial palivizumab
Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or lower respiratory illness within 7 days prior to randomization
Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of randomization
Active RSV infection (a child with signs/symptoms of respiratory infection must have negative RSV testing) or known prior history of RSV infection
Receipt of palivizumab or any RSV vaccine, including maternal RSV vaccination

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDI8897 10 mg	MEDI8897 10 mg	Participants will receive a single dose of MEDI8897 10 milligram (mg) intramuscularly.
Placebo	Placebo	Participants will receive placebo intramuscularly.
MEDI8897 25 mg	MEDI8897 25 mg	Participants will receive a single dose of MEDI8897 25 mg intramuscularly.
MEDI8897 50 mg	MEDI8897 50 mg	Participants will receive a single dose of MEDI8897 50 mg intramuscularly.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity of a participant who received MEDI8897. TEAEs and TESAEs were the events that occurred between administration of study drug (Day 1) and Day 361 that were absent before treatment or that worsened relative to pre-treatment state.
Number of Participants With Treatment-Emergent Adverse Events of Special Interest	From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	An AESI was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator (that is, within 24 hrs of knowledge of the event) to the sponsor. The AESIs for this study were hepatic function abnormality meeting the definition of Hy's law, hypersensitivity reactions including anaphylaxis, immune complex disease, and thrombocytopenia. Treatment-emergent AESIs were collected from the time of dosing until Day 361 post-dose.
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events	From Study Drug Administration (Day 1) Through the Follow-up Period (Day 151)	Laboratory abnormalities determined by the investigator to be clinically significant that occurred after study drug dosing through 151 days post-dose that were absent before treatment or that worsened relative to pre-treatment state were reported as TEAEs. Laboratory evaluations (haematology and serum chemistry) of blood samples were performed.

Secondary Outcome Measures

Name	Time	Method
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI8897	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose	The Tmax defined as time at which maximum observed concentration of MEDI8897 (Cmax) was observed.
Maximum Observed Serum Concentration (Cmax) of MEDI8897	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose	The Cmax is the maximum observed serum concentration of MEDI8897.
Area Under the Concentration-Time Curve From Day 1 to Day 151 (AUC [1-151]) of MEDI8897	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), and 150 (± 7) Post-dose	Area under the concentration-time curve of the MEDI8897 in serum over the time interval from day 1 to day 151 (AUC1-151).
Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI8897	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose	The pharmacokinetic (PK) parameter AUC (0-infinity) was estimated based on the serum concentrations of MEDI8897.
Terminal Elimination Half Life (t1/2) of MEDI8897	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose	Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.
Extravascular Clearance (CL/F) of MEDI8897	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
Extravascular Volume of Distribution (Vz/F) of MEDI8897	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.
Number of Participants Positive for Anti-Drug Antibodies to MEDI8897	Pre-dose at Baseline (Days -7 to -1) and on Days 31, 151, and 361 Post-dose	A participant was considered ADA-positive if the participant had a positive reading at any time point post baseline. Titers greater than or equal to 50 were considered positive.