Back to resultsA 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)
Primary Purpose
Respiratory Syncytial Virus
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Placebo
MEDI8897 10 mg
MEDI8897 25 mg
MEDI8897 50 mg
Sponsored by
About this trial
This is an interventional prevention trial for Respiratory Syncytial Virus focused on measuring Respiratory Syncytial Virus, RSV
Eligibility Criteria
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo
MEDI8897 10 mg
MEDI8897 25 mg
MEDI8897 50 mg
Arm Description
Participants will receive placebo intramuscularly.
Participants will receive a single dose of MEDI8897 10 milligram (mg) intramuscularly.
Participants will receive a single dose of MEDI8897 25 mg intramuscularly.
Participants will receive a single dose of MEDI8897 50 mg intramuscularly.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
Maximum Observed Serum Concentration (Cmax) of MEDI8897
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
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
The pharmacokinetic (PK) parameter AUC (0-infinity) was estimated based on the serum concentrations of MEDI8897.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02290340
Brief Title
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
Acronym
MEDI8897 1b
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
January 13, 2015 (Actual)
Primary Completion Date
September 28, 2016 (Actual)
Study Completion Date
September 28, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Syncytial Virus
Keywords
Respiratory Syncytial Virus, RSV
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
151 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo intramuscularly.
Arm Title
MEDI8897 10 mg
Arm Type
Experimental
Arm Description
Participants will receive a single dose of MEDI8897 10 milligram (mg) intramuscularly.
Arm Title
MEDI8897 25 mg
Arm Type
Experimental
Arm Description
Participants will receive a single dose of MEDI8897 25 mg intramuscularly.
Arm Title
MEDI8897 50 mg
Arm Type
Experimental
Arm Description
Participants will receive a single dose of MEDI8897 50 mg intramuscularly.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive placebo intramuscularly.
Intervention Type
Drug
Intervention Name(s)
MEDI8897 10 mg
Intervention Description
Participants will receive a single dose of MEDI8897 10 milligram (mg) intramuscularly.
Intervention Type
Drug
Intervention Name(s)
MEDI8897 25 mg
Intervention Description
Participants will receive a single dose of MEDI8897 25 mg intramuscularly.
Intervention Type
Drug
Intervention Name(s)
MEDI8897 50 mg
Intervention Description
Participants will receive a single dose of MEDI8897 50 mg intramuscularly.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Description
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.
Time Frame
From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Title
Number of Participants With Treatment-Emergent Adverse Events of Special Interest
Description
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.
Time Frame
From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Title
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events
Description
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.
Time Frame
From Study Drug Administration (Day 1) Through the Follow-up Period (Day 151)
Secondary Outcome Measure Information:
Title
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI8897
Description
The Tmax defined as time at which maximum observed concentration of MEDI8897 (Cmax) was observed.
Time Frame
Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Title
Maximum Observed Serum Concentration (Cmax) of MEDI8897
Description
The Cmax is the maximum observed serum concentration of MEDI8897.
Time Frame
Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Title
Area Under the Concentration-Time Curve From Day 1 to Day 151 (AUC [1-151]) of MEDI8897
Description
Area under the concentration-time curve of the MEDI8897 in serum over the time interval from day 1 to day 151 (AUC1-151).
Time Frame
Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), and 150 (± 7) Post-dose
Title
Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI8897
Description
The pharmacokinetic (PK) parameter AUC (0-infinity) was estimated based on the serum concentrations of MEDI8897.
Time Frame
Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Title
Terminal Elimination Half Life (t1/2) of MEDI8897
Description
Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.
Time Frame
Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Title
Extravascular Clearance (CL/F) of MEDI8897
Description
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame
Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Title
Extravascular Volume of Distribution (Vz/F) of MEDI8897
Description
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.
Time Frame
Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
Title
Number of Participants Positive for Anti-Drug Antibodies to MEDI8897
Description
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.
Time Frame
Pre-dose at Baseline (Days -7 to -1) and on Days 31, 151, and 361 Post-dose
10. Eligibility
Sex
All
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
Research Site
City
Anaheim
State/Province
California
Country
United States
Facility Name
Research Site
City
Ontario
State/Province
California
Country
United States
Facility Name
Research Site
City
Syracuse
State/Province
New York
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Charleston
State/Province
South Carolina
Country
United States
Facility Name
Research Site
City
Saint George
State/Province
Utah
Country
United States
Facility Name
Research Site
City
Marshfield
State/Province
Wisconsin
Country
United States
Facility Name
Research Site
City
Santiago
Country
Chile
Facility Name
Research Site
City
Valdivia
Country
Chile
Facility Name
Research Site
City
Cape Town
Country
South Africa
Facility Name
Research Site
City
East London
Country
South Africa
Facility Name
Research Site
City
Johannesburg
Country
South Africa
Facility Name
Research Site
City
Pretoria
Country
South Africa
12. IPD Sharing Statement
Learn more about this trial
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
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