A Phase 2a to Evaluate the Safety of MEDI8852 in Adults With Uncomplicated Influenza (MEDI8852)

A Phase 2a, Randomized, Partial Double-blind, Single Dose, Active-controlled, Dose Ranging Study to Evaluate the Safety of MEDI8852 in Adults With Acute, Uncomplicated Influenza

The purpose of this study is to evaluate safety and tolerability of a single dose of MEDI8852 when given with oseltamivir, the safety and tolerability of oseltamivir alone, and the safety and tolerability of a single dose of MEDI8852 alone in adult participants with acute, uncomplicated influenza caused by Type A strains.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: Oseltamivir; Drug: Placebo; Drug: MEDI8852

Detailed Description

The MEDI8852 phase 2a study will evaluate the safety and tolerability of a single intravenous (IV) dose of MEDI8852 administered in conjunction with oseltamivir, the safety and tolerability of oseltamivir alone and the safety and tolerability of a single IV dose of MEDI8852 alone in adult participants with confirmed acute, uncomplicated influenza caused by Type A strains. Enrollment is planned in the United States, South Africa, and Australia.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Brandfort, South Africa, 9400
    • Research Site
  • Durban, South Africa, 4001
    • Research Site
  • Johannesburg, South Africa, 2113
    • Research Site
  • Pretoria, South Africa, 0157
    • Research Site
  • Pretoria, South Africa, 0181
    • Research Site
  • Pretoria, South Africa, 0183
    • Research Site
  • Pretoria, South Africa, 0087
    • Research Site
  • Thabazimbi, South Africa, 0380
    • Research Site
  • Welkom, South Africa, 9460
    • Research Site
• United States
  • California
    • Canoga Park, California, United States, 91303
      • Research Site
    • Long Beach, California, United States, 90806
      • Research Site
    • Los Angeles, California, United States, 90017
      • Research Site
    • Upland, California, United States, 91786
      • Research Site
  • Florida
    • Hialeah, Florida, United States, 33012
      • Research Site
    • Hialeah, Florida, United States, 33013
      • Research Site
    • Hialeah, Florida, United States, 33016
      • Research Site
    • Miami, Florida, United States, 33173
      • Research Site
    • Miami, Florida, United States, 33165
      • Research Site
    • Miami, Florida, United States, 33185
      • Research Site
    • Miami Lakes, Florida, United States, 33014
      • Research Site
    • North Miami Beach, Florida, United States, 33162
      • Research Site
  • Indiana
    • Avon, Indiana, United States, 46123
      • Research Site
    • Muncie, Indiana, United States, 47304
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70124
      • Research Site
  • Michigan
    • Troy, Michigan, United States, 48085
      • Research Site
  • Montana
    • Butte, Montana, United States, 59701
      • Research Site
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • Research Site
    • Shelby, North Carolina, United States, 28150
      • Research Site
  • Pennsylvania
    • Smithfield, Pennsylvania, United States, 15478
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Utah
    • Clinton, Utah, United States, 84015
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 through 65 years at the time of screening.
• Symptomatic presumptive Influenza A infection with onset of symptoms less than or equal to (≤) 5 days prior to MEDI8852 administration and defined as the presence of:
• Fever of greater than or equal to (≥) 38.0 degrees Celsius (100.4 degrees Fahrenheit) at screening AND
• ≥ 1 moderate systemic symptom (headache, malaise, myalgia, sweats and/or chills, or fatigue) AND
• ≥ 1 moderate respiratory symptom (cough, sore throat, or nasal symptoms)
• Influenza A infection confirmed with positive rapid antigen test
• Able to complete the follow-up period through Day 101 as required by protocol (including telephone follow-up for Days 11 to 101)
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for at least 2 days prior to the first dose of investigational product and must agree to continue using such precautions through Day 101 of the study

Exclusion Criteria:

• Hospitalized subjects.
• Receipt of influenza antiviral therapy within the preceding 14 days.
• Receipt of immunoglobulin or blood products within 6 months prior to screening.
• Known immunodeficiency due to illness, including human immunodeficiency virus (HIV), or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening.
• Current clinical evidence of pneumonia.
• Active bacterial infection requiring treatment with oral or parenteral antibiotics.
• History of malignancy other than treated non-melanoma skin cancers or locally-treated cervical cancer in previous 3 years.
• Any planned surgical procedure before completion of Day 101.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + Oseltamivir 75 mg; Participants will receive a single intravenous (IV) infusion of placebo (matched to MEDI8852) on Day 1 and oseltamivir 75 milligrams (mg) capsules orally twice a day (BID) from Day 1 to Day 5.	Drug: Oseltamivir; 75 mg capsules orally BID from Day 1 to Day 5.; Drug: Placebo; Placebo is salt-water solution containing no active ingredients and administered as a single IV infusion on Day 1.
Experimental: MEDI8852 750 mg + Oseltamivir 75 mg; Participants will receive a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Drug: Oseltamivir; 75 mg capsules orally BID from Day 1 to Day 5.; Drug: MEDI8852; MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.
Experimental: MEDI8852 3000 mg + Oseltamivir 75 mg; Participants will receive a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Drug: Oseltamivir; 75 mg capsules orally BID from Day 1 to Day 5.; Drug: MEDI8852; MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.
Experimental: MEDI8852 3000 mg; Participants will receive a single IV infusion of MEDI8852 3000 mg on Day 1.	Drug: MEDI8852; MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Solicited Influenza Symptoms From Day 1 Through Day 10	Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).	Day 1 (post-dose) through Day 10
Number of Participants With Any Solicited Influenza Symptoms From Day 10 Through Day 13	Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).	Day 10 through Day 13
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent events were between administration of study drug and Day 28 that were absent before treatment or that worsened relative to pre-treatment state.	Day 1 (post-dose) through Day 28
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs)	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 experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events were between administration of study drug and Day 101 that were absent before treatment or that worsened relative to pre-treatment state.	Day 1 (post-dose) through Day 101
Number of Participants With Treatment Emergent Adverse Events of Special Interest (TEAESIs)	An AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. An AESI was one of scientific and medical interest specific to understanding of the study drug and may have required close monitoring and rapid communication by the investigator to the sponsor. Treatment-emergent events were between administration of study drug and Day 101 that were absent before treatment or that worsened relative to pre treatment state.	Day 1 (post-dose) through Day 101

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Influenza Viral Shedding as Measured by Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR)	Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure influenza viral shedding from the nasopharyngeal swabs. Percentage of participants who shed influenza virus are reported.	Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13
Quantitation of Influenza Viral Shedding as Measured by qRT-PCR	qRT-PCR was used to measure influenza viral shedding from the nasopharyngeal swabs.	Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13
Number of Days of Influenza Viral Shedding as Measured by qRT-PCR	Number of days of viral shedding for participants who shed influenza virus is reported. qRT-PCR was used to measure influenza viral shedding from the nasopharyngeal swabs.	From Baseline (Day 1) to Day 7; and Day 9 to Day 13
Percentage of Participants With Amino Acid Changes in MEDI8852 Binding Site	Genotypic analysis was performed to identify all amino acid changes in MEDI8852 binding site between each baseline (Day1) sample and the participant's corresponding last sample sequenced. Percentage of participants with changes in the amino acid corresponding to MEDI8852 binding site is reported. Due to the fact that the percentage of participants with amino acid changes in MEDI8852 binding site was zero across all participant samples analyzed, no additional per arm analyses were performed.	From Baseline (Day 1) to Day 13
Number of Participants With Viral Susceptibility to MEDI8852 as Determined by a Cell Based Microneutralization Assay	Viral susceptibility to MEDI8852 was measured by a Madin-Darby canine kidney (MDCK) cell-based microneutralization assay (Virospot) for viruses recovered from baseline samples and viruses recovered from samples following treatment that contain amino acid changes within the MEDI8852 binding site. Participants with detectable levels (50% tissue culture infectious dose [TCID50]) of virus were considered susceptible and were reported. Due to the fact that the number of participants with viral susceptibility to MEDI8852 binding site was zero across all participant samples analyzed, no additional per arm analyses were performed.	From Baseline (Day 1) to Day 13
Percentage of Participants With Virus Containing Known Oseltamivir Resistance-Associated Mutations	Genotypic analysis was performed to identify all amino acid changes in neuraminidase (NA) gene between each baseline (Day1) sample and the participant's corresponding last sample sequenced. Percentage of participants with virus containing known oseltamivir resistance-associated mutations (change in the NA genes) is reported. Due to the fact that the percentage of participants with virus containing known oseltamivir resistance-associated mutation was zero across all participant samples analyzed, no additional per arm analyses were performed.	From Baseline (Day 1) to Day 13

Collaborators and Investigators

• Sponsor: MedImmune LLC

Publications and helpful links

General Publications

• Ali SO, Takas T, Nyborg A, Shoemaker K, Kallewaard NL, Chiong R, Dubovsky F, Mallory RM. Evaluation of MEDI8852, an Anti-Influenza A Monoclonal Antibody, in Treating Acute Uncomplicated Influenza. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e00694-18. doi: 10.1128/AAC.00694-18. Print 2018 Nov.

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2015
• Primary Completion (Actual): December 9, 2016
• Study Completion (Actual): December 9, 2016

Study Registration Dates

• First Submitted: November 2, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (Estimate): November 13, 2015

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: May 7, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Influenza; Influenza A; Flu; Flu A
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir; MEDI8852
• Other Study ID Numbers: D6000C00002