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 (MEDI8897 1b)

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus
• Intervention / Treatment: Drug: Placebo; Drug: MEDI8897 10 mg; Drug: MEDI8897 25 mg; Drug: MEDI8897 50 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 1

Contacts and Locations

Study Locations

• Chile
  • Santiago, Chile
    • Research Site
  • Valdivia, Chile
    • Research Site
• South Africa
  • Cape Town, South Africa
    • Research Site
  • East London, South Africa
    • Research Site
  • Johannesburg, South Africa
    • Research Site
  • Pretoria, South Africa
    • Research Site
• United States
  • California
    • Anaheim, California, United States
      • Research Site
    • Ontario, California, United States
      • Research Site
  • New York
    • Syracuse, New York, United States
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States
      • Research Site
  • Utah
    • Saint George, Utah, United States
      • Research Site
  • Wisconsin
    • Marshfield, Wisconsin, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo intramuscularly.	Drug: Placebo; Participants will receive placebo intramuscularly.
Experimental: MEDI8897 10 mg; Participants will receive a single dose of MEDI8897 10 milligram (mg) intramuscularly.	Drug: MEDI8897 10 mg; Participants will receive a single dose of MEDI8897 10 milligram (mg) intramuscularly.
Experimental: MEDI8897 25 mg; Participants will receive a single dose of MEDI8897 25 mg intramuscularly.	Drug: MEDI8897 25 mg; Participants will receive a single dose of MEDI8897 25 mg intramuscularly.
Experimental: MEDI8897 50 mg; Participants will receive a single dose of MEDI8897 50 mg intramuscularly.	Drug: MEDI8897 50 mg; Participants will receive a single dose of MEDI8897 50 mg intramuscularly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	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.	From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Number of Participants With Treatment-Emergent Adverse Events of Special Interest	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.	From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events	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.	From Study Drug Administration (Day 1) Through the Follow-up Period (Day 151)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI8897	The Tmax defined as time at which maximum observed concentration of MEDI8897 (Cmax) was observed.	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Maximum Observed Serum Concentration (Cmax) of MEDI8897	The Cmax is the maximum observed serum concentration of MEDI8897.	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Area Under the Concentration-Time Curve From Day 1 to Day 151 (AUC [1-151]) of MEDI8897	Area under the concentration-time curve of the MEDI8897 in serum over the time interval from day 1 to day 151 (AUC1-151).	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 From Zero to Infinity (AUC [0-infinity]) of MEDI8897	The pharmacokinetic (PK) parameter AUC (0-infinity) was estimated based on the serum concentrations 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 Elimination Half Life (t1/2) of MEDI8897	Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Extravascular Clearance (CL/F) of MEDI8897	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Extravascular Volume of Distribution (Vz/F) of MEDI8897	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.	Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Number of Participants Positive for Anti-Drug Antibodies to MEDI8897	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.	Pre-dose at Baseline (Days -7 to -1) and on Days 31, 151, and 361 Post-dose

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2015
• Primary Completion (Actual): September 28, 2016
• Study Completion (Actual): September 28, 2016

Study Registration Dates

• First Submitted: October 17, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 14, 2014

Study Record Updates

• Last Update Posted (Actual): September 19, 2018
• Last Update Submitted That Met QC Criteria: September 18, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Respiratory Syncytial Virus, RSV
• Additional Relevant MeSH Terms: Infections; Virus Diseases
• Other Study ID Numbers: D5290C00002