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

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Drug: MEDI8897 Intravenous; Drug: MEDI8897 Intravenous; Drug: MEDI8897 Intravenous; Drug: MEDI8897 Intramuscular; Drug: MEDI8897 Intramuscular; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 342
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI8897 300 milligram (mg) Intravenous (IV); Participants received a single fixed dose of 300 mg MEDI8897 intravenous infusion on Day 1.	Drug: MEDI8897 Intravenous; Participants received a single fixed dose of 300 mg MEDI8897 intravenous infusion on Day 1.; Drug: MEDI8897 Intravenous; Participants received a single fixed dose of 1000 mg MEDI8897 intravenous infusion on Day 1.; Drug: MEDI8897 Intravenous; Participants received a single fixed dose of 3000 mg MEDI8897 intravenous infusion on Day 1.
Experimental: MEDI8897 1000 mg IV; Participants received a single fixed dose of 1000 mg MEDI8897 intravenous infusion on Day 1.	Drug: MEDI8897 Intravenous; Participants received a single fixed dose of 300 mg MEDI8897 intravenous infusion on Day 1.; Drug: MEDI8897 Intravenous; Participants received a single fixed dose of 1000 mg MEDI8897 intravenous infusion on Day 1.; Drug: MEDI8897 Intravenous; Participants received a single fixed dose of 3000 mg MEDI8897 intravenous infusion on Day 1.
Experimental: MEDI8897 3000 mg IV; Participants received a single fixed dose of 3000 mg MEDI8897 intravenous infusion on Day 1.	Drug: MEDI8897 Intravenous; Participants received a single fixed dose of 300 mg MEDI8897 intravenous infusion on Day 1.; Drug: MEDI8897 Intravenous; Participants received a single fixed dose of 1000 mg MEDI8897 intravenous infusion on Day 1.; Drug: MEDI8897 Intravenous; Participants received a single fixed dose of 3000 mg MEDI8897 intravenous infusion on Day 1.
Experimental: MEDI8897 100 mg Intramuscular (IM); Participants received a single fixed dose of 100 mg MEDI8897 intramuscular injection on Day 1.	Drug: MEDI8897 Intramuscular; Participants received a single fixed dose of 100 mg MEDI8897 intramuscular injection on Day 1.; Drug: MEDI8897 Intramuscular; Participants received a single fixed dose of 300 mg MEDI8897 intramuscular injection on Day 1.
Experimental: MEDI8897 300 mg IM; Participants received a single fixed dose of 300 mg MEDI8897 intramuscular injection on Day 1.	Drug: MEDI8897 Intramuscular; Participants received a single fixed dose of 100 mg MEDI8897 intramuscular injection on Day 1.; Drug: MEDI8897 Intramuscular; Participants received a single fixed dose of 300 mg MEDI8897 intramuscular injection on Day 1.
Placebo Comparator: Placebo; Participants received placebo on Day 1.	Drug: Placebo; Participants received placebo on Day 1.

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 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

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: M. Pamela Griffin, MD, MedImmune LLC; Principal Investigator: Martin Kankam, MD, PhD, MPH, Study Site

Publications and helpful links

General Publications

• Griffin MP, Khan AA, Esser MT, Jensen K, Takas T, Kankam MK, Villafana T, Dubovsky F. Safety, Tolerability, and Pharmacokinetics of MEDI8897, the Respiratory Syncytial Virus Prefusion F-Targeting Monoclonal Antibody with an Extended Half-Life, in Healthy Adults. Antimicrob Agents Chemother. 2017 Feb 23;61(3):e01714-16. doi: 10.1128/AAC.01714-16. Print 2017 Mar.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: April 3, 2014
• First Submitted That Met QC Criteria: April 11, 2014
• First Posted (Estimate): April 15, 2014

Study Record Updates

• Last Update Posted (Estimate): November 28, 2016
• Last Update Submitted That Met QC Criteria: October 5, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Respiratory Syncytial Virus, RSV
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: D5290C00001