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

Influenza Clinical Trial

— MEDI8852  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02603952
• Other study ID #: D6000C00002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 7, 2015
• Est. completion date: December 9, 2016

Study information

• Verified date: May 2018
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: December 9, 2016
• Est. primary completion date: December 9, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Drug:
• Oseltamivir
75 mg capsules orally BID from Day 1 to Day 5.
• 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.
• Placebo
Placebo is salt-water solution containing no active ingredients and administered as a single IV infusion on Day 1.

Locations

Country	Name	City	State
South Africa	Research Site	Brandfort
South Africa	Research Site	Durban
South Africa	Research Site	Johannesburg
South Africa	Research Site	Pretoria
South Africa	Research Site	Pretoria
South Africa	Research Site	Pretoria
South Africa	Research Site	Pretoria
South Africa	Research Site	Thabazimbi
South Africa	Research Site	Welkom
United States	Research Site	Avon	Indiana
United States	Research Site	Butte	Montana
United States	Research Site	Canoga Park	California
United States	Research Site	Clinton	Utah
United States	Research Site	Hialeah	Florida
United States	Research Site	Hialeah	Florida
United States	Research Site	Hialeah	Florida
United States	Research Site	Hickory	North Carolina
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Muncie	Indiana
United States	Research Site	New Orleans	Louisiana
United States	Research Site	North Miami Beach	Florida
United States	Research Site	San Antonio	Texas
United States	Research Site	Shelby	North Carolina
United States	Research Site	Smithfield	Pennsylvania
United States	Research Site	Troy	Michigan
United States	Research Site	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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