Phase 1 Single-ascending Dose Study to Evaluate Safety and Tolerability of MEDI4920 in Healthy Adults

A Phase 1, Randomized, Blinded, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI4920 in Healthy Adults

Phase 1 single IV dose study to evaluate safety and tolerability of MEDI4920

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Other: Placebo; Biological: MEDI4920 3 mg; Biological: MEDI4920 10 mg; Biological: MEDI4920 30 mg; Biological: MEDI4920 100 mg; Biological: MEDI4920 300 mg; Biological: MEDI4920 1000 mg; Biological: MEDI4920 3000 mg

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • 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

Inclusion Criteria:

• Healthy as determined by a responsible study physician based on medical evaluation
• Body weight 40 to 100 kg
• Body mass index 19.0 to 30.0 kg/m2

Exclusion Criteria:

• History of allergy or sensitivity to Shellfish or protein based antigens
• previous immunization with KLH
• previous splenectomy
• History of diagnosed or suspected thromboembolic event or coagulation disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received single IV dose of placebo matching with MEDI4920 infused on Day 1.	Other: Placebo; Participants received single IV dose of placebo matching with MEDI4920 infused on Day 1.
Experimental: MEDI4920 3 mg; Participants received single IV dose of MEDI4920 3 milligram (mg) infused on Day 1.	Biological: MEDI4920 3 mg; Participants received single IV dose of MEDI4920 3 milligram (mg) infused on Day 1.
Experimental: MEDI4920 10 mg; Participants received single IV dose of MEDI4920 10 mg infused on Day 1.	Biological: MEDI4920 10 mg; Participants received single IV dose of MEDI4920 10 mg infused on Day 1.
Experimental: MEDI4920 30 mg; Participants received single IV dose of MEDI4920 30 mg infused on Day 1.	Biological: MEDI4920 30 mg; Participants received single IV dose of MEDI4920 30 mg infused on Day 1.
Experimental: MEDI4920 100 mg; Participants received single IV dose of MEDI4920 100 mg infused on Day 1.	Biological: MEDI4920 100 mg; Participants received single IV dose of MEDI4920 100 mg infused on Day 1.
Experimental: MEDI4920 300 mg; Participants received single IV dose of MEDI4920 300 mg infused on Day 1.	Biological: MEDI4920 300 mg; Participants received single IV dose of MEDI4920 300 mg infused on Day 1.
Experimental: MEDI4920 1000 mg; Participants received single IV dose of MEDI4920 1000 mg infused on Day 1.	Biological: MEDI4920 1000 mg; Participants received single IV dose of MEDI4920 1000 mg infused on Day 1.
Experimental: MEDI4920 3000 mg; Participants received single IV dose of MEDI4920 3000 mg infused on Day 1.	Biological: MEDI4920 3000 mg; Participants received single IV dose of MEDI4920 3000 mg infused 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 any unfavourable 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 or incapacity; congenital anomaly or birth defect in the offspring of a participant who received the study drug. A TEAE is defined as the event with onset after the start of infusion (Day 1) to Day 113 or early discontinuation visit inclusive. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0.	The start of study drug administration (Day 1) to the follow-up period (Day 113) or early discontinuation visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of MEDI4920	The maximum observed plasma concentration (Cmax) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.	Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI4920	The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.	Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI4920	The area under the plasma concentration-time curve from time zero to infinity (AUC 0-inf) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.	Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Dose-normalized AUC0-inf (AUC0-infinity/D) of MEDI4920	The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity postdose normalized by MEDI4920 dose. The AUC (0-infinity)/D was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.	Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Terminal Elimination Half Life (t1/2) of MEDI4920	The terminal elimination half-life (t1/2) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.	Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Systemic Clearance (CL) of MEDI4920	The systemic clearance (CL) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.	Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Volume of Distribution at Steady-state (Vss) of MEDI4920	The volume of distribution at steady-state (Vss) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.	Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Volume of Distribution Based on Terminal Phase (Vz) of MEDI4920	The volume of distribution based on terminal phase (Vz) was estimated based on the plasma concentrations of MEDI4920. Standard deviation was calculated only if number of participants were more than or equal to 3.	Pre-infusion, at the middle of the infusion, post-infusion (5 minutes, and 2, 6, and 12 hours) on Day 1; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 85, and 113 or early discontinuation visit, whichever occurred first
Percentage of Participants Positive for Anti-drug Antibodies (ADA)	Plasma samples were collected for assessment of anti-drug antibodies (ADA) against MEDI4920. The incidence of positive serum antibodies to MEDI4920 are presented.	Baseline (pre-infusion on Day 1) and post-baseline Days 15, 29, 57, and 113 or early discontinuation visit, whichever occurred first
T-cell Dependent Antibody Response (TDAR) Measured by Anti-keyhole Limpet Hemocyanin Immunoglobulin G (Anti-KLH IgG) Concentration	The T-cell dependent antibody response (TDAR) assay measures the immune response (ie, antibody production) to an introduced antigen, keyhole limpet hemocyanin (KLH). The KLH is a potent immunostimulating protein with an extensive history of safe and effective use in vaccine development and immunological research. TDAR was evaluated by measuring anti-KLH IgG titers at a time point consistent with the expected timing for antibody responses following immunization. The primary time point for the analysis of the TDAR to KLH was Day 43. The data was presented for geometric mean ratio (MEDI4920/placebo) estimated from the dose response model.	Day 43

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2014
• Primary Completion (Actual): May 9, 2016
• Study Completion (Actual): May 9, 2016

Study Registration Dates

• First Submitted: May 27, 2014
• First Submitted That Met QC Criteria: May 29, 2014
• First Posted (Estimate): May 30, 2014

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: October 2, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Healthy Male; Healthy Female of non child bearing potential
• Other Study ID Numbers: D5100C00001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No