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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)

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ClinicalTrials.gov Identifier: NCT02290340
Recruitment Status : Completed
First Posted : November 14, 2014
Results First Posted : September 19, 2018
Last Update Posted : September 19, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus Drug: Placebo Drug: MEDI8897 10 mg Drug: MEDI8897 25 mg Drug: MEDI8897 50 mg Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 151 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Actual Study Start Date : January 13, 2015
Actual Primary Completion Date : September 28, 2016
Actual Study Completion Date : September 28, 2016

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.




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: 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.

  2. Number of Participants With Treatment-Emergent Adverse Events of Special Interest [ Time Frame: 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.

  3. Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events [ Time Frame: 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 :
  1. Time to Reach Maximum Observed Serum Concentration (Tmax) 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 ]
    The Tmax defined as time at which maximum observed concentration of MEDI8897 (Cmax) was observed.

  2. Maximum Observed Serum Concentration (Cmax) 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 ]
    The Cmax is the maximum observed serum concentration of MEDI8897.

  3. Area Under the Concentration-Time Curve From Day 1 to Day 151 (AUC [1-151]) of MEDI8897 [ Time Frame: 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).

  4. Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) 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 ]
    The pharmacokinetic (PK) parameter AUC (0-infinity) was estimated based on the serum concentrations of MEDI8897.

  5. Terminal Elimination Half Life (t1/2) 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 ]
    Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.

  6. Extravascular Clearance (CL/F) 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 ]
    Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.

  7. Extravascular Volume of Distribution (Vz/F) 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 ]
    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.

  8. Number of Participants Positive for Anti-Drug Antibodies to MEDI8897 [ Time Frame: 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.



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Ages Eligible for Study:   up to 12 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02290340


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

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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02290340     History of Changes
Other Study ID Numbers: D5290C00002
First Posted: November 14, 2014    Key Record Dates
Results First Posted: September 19, 2018
Last Update Posted: September 19, 2018
Last Verified: September 2018
Keywords provided by MedImmune LLC:
Respiratory Syncytial Virus, RSV
Additional relevant MeSH terms:
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Virus Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs