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 Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Respiratory Syncytial Virus

Intervention / Treatment
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* Drug: Placebo
* Drug: MEDI8897 10 mg
* Drug: MEDI8897 25 mg
* Drug: MEDI8897 50 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Syncytial Virus, RSV