A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI8897 in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this study was 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 adult participants.

Detailed Description
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This was a phase 1, randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, tolerability and pharmacokinetics of MEDI8897 compared to placebo when administered to healthy adult participants. There were 136 participants randomized to receive MEDI8897 or placebo at one site. Investigational product was delivered intravenously (IV) to 3 cohorts and intramuscularly (IM) to 2 cohorts. 4 different dose levels of investigational product were evaluated across the 5 cohorts. Participants were followed for approximately 1 year.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI8897 in Healthy Adults

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Drug: MEDI8897 Intravenous
* Drug: Placebo
* Drug: MEDI8897 Intravenous
* Drug: MEDI8897 Intravenous
* Drug: MEDI8897 Intramuscular
* Drug: MEDI8897 Intramuscular


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age 18 through 49 years and in good health by history, physical exam, and labs Weight greater than or equal to (>=) 45 kilogram (kg) and less than or equal to (<=) 110 kg at Screening Written informed consent prior to performing any protocol related procedures, including Screening evaluations Ability to complete the Follow-up period of 360 days Key Exclusion Criteria: Acute illness including fever >= 99.5 Fahrenheit (°F) on day of dosing Any drug therapy within 7 days prior to Day 1 (except contraceptives) Receipt of any investigational drug therapy within 120 days prior to investigational product dosing through 360 days after investigational product dosing Previous receipt of a monoclonal antibody (mAb) Pregnant or nursing mother Concurrent enrollment in another interventional study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI8897 300 milligram (mg) Intravenous (IV)<br>Participants received a single fixed dose of 300 mg MEDI8897 intravenous infusion on Day 1. | Drug: MEDI8897 Intravenous<br>* Participants received a single fixed dose of 300 mg MEDI8897 intravenous infusion on Day 1.<br>|
| Experimental: MEDI8897 1000 mg IV<br>Participants received a single fixed dose of 1000 mg MEDI8897 intravenous infusion on Day 1. | Drug: MEDI8897 Intravenous<br>* Participants received a single fixed dose of 1000 mg MEDI8897 intravenous infusion on Day 1.<br>|
| Experimental: MEDI8897 3000 mg IV<br>Participants received a single fixed dose of 3000 mg MEDI8897 intravenous infusion on Day 1. | Drug: MEDI8897 Intravenous<br>* Participants received a single fixed dose of 3000 mg MEDI8897 intravenous infusion on Day 1.<br>|
| Experimental: MEDI8897 100 mg Intramuscular (IM)<br>Participants received a single fixed dose of 100 mg MEDI8897 intramuscular injection on Day 1. | Drug: MEDI8897 Intramuscular<br>* Participants received a single fixed dose of 100 mg MEDI8897 intramuscular injection on Day 1.<br>|
| Experimental: MEDI8897 300 mg IM<br>Participants received a single fixed dose of 300 mg MEDI8897 intramuscular injection on Day 1. | Drug: MEDI8897 Intramuscular<br>* Participants received a single fixed dose of 300 mg MEDI8897 intramuscular injection on Day 1.<br>|
| Placebo Comparator: Placebo<br>Participants received placebo on Day 1. | Drug: Placebo<br>* Participants received placebo on Day 1.<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 defined as events present at baseline that worsened in intensity after administration of investigational products or events absent at baseline that emerged after administration of study drug, for the period extending to 391 (Day 361 ± 30 days) days after the last dose of study drug. | From start of study drug administration up to Day 391 (Day 361 +/- 30 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI8897 | The Tmax is defined as actual sampling time to reach maximum observed MEDI8897 concentration. The reported Standard Deviation values are actually Relative Standard Deviation (RSD) values (that is, Coefficient of Variation). | Predose, End of Dosing (IV Arms), 8 Hour Postdose, Day 2, 4, 6, 8, 15, 22, 31, 61, 91, 121, 151, 181, 271 and 361 | 
| Maximum Observed Serum Concentration (Cmax) for MEDI8897 | The Cmax is the maximum observed serum concentration of MEDI8897. The reported Standard Deviation values are actually Relative Standard Deviation (RSD) values (that is, Coefficient of Variation). | Predose, End of Dosing (IV Arms), 8 Hour Postdose, Day 2, 4, 6, 8, 15, 22, 31, 61, 91, 121, 151, 181, 271 and 361 | 
| Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) for MEDI8897 | The AUC (0-infinity) is the area under the serum concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the serum concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant. The reported Standard Deviation values are actually Relative Standard Deviation (RSD) values (that is, Coefficient of Variation). | Predose, End of Dosing (IV Arms), 8 Hour Postdose, Day 2, 4, 6, 8, 15, 22, 31, 61, 91, 121, 151, 181, 271 and 361 | 
| Terminal Phase Elimination Half Life (t1/2) for MEDI8897 | The terminal elimination half-life (t1/2) is the time measured for the serum concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z). Here 'n' signifies participants evaluable for specified categories, for each arm, respectively. The reported Standard Deviation values are actually Relative Standard Deviation (RSD) values (that is, Coefficient of Variation). | Predose, End of Dosing (IV Arms), 8 Hour Postdose, Day 2, 4, 6, 8, 15, 22, 31, 61, 91, 121, 151, 181, 271 and 361 | 
| Systemic Clearance (CL) for MEDI8897 | Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after the dose was estimated by dividing the total administered dose by the Area Under the Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]). Apparent clearance (CL/F) for the IM dose groups. The reported Standard Deviation values are actually Relative Standard Deviation (RSD) values (that is, Coefficient of Variation). | Predose, End of Dosing (IV Arms), 8 Hour Postdose, Day 2, 4, 6, 8, 15, 22, 31, 61, 91, 121, 151, 181, 271 and 361 | 
| Volume of Distribution (Vz) for MEDI8897 | The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a study drug. Apparent volume of distribution (Vz/F) for the IM dose groups. The reported Standard Deviation values are actually Relative Standard Deviation (RSD) values (that is, Coefficient of Variation). | Predose, End of Dosing (IV Arms), 8 Hour Postdose, Day 2, 4, 6, 8, 15, 22, 31, 61, 91, 121, 151, 181, 271 and 361 | 
| Number of Participants With Positive Anti-Drug Antibody (ADA) | Participants were tested for anti-drug antibody to MEDI8897 prior to enrollment, predose and postdose. | Predose and Day 15, 31, 91, 181, 271 and 361 | 

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