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

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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02603952

Acronym

MEDI8852

Enrollment

126

Registered

2015-11-13

Start date

2015-12-07

Completion date

2016-12-09

Last updated

2018-06-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Influenza

Keywords

Influenza, Influenza A, Flu, Flu A

Brief 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.

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.

Interventions

DRUGOseltamivir

75 mg capsules orally BID from Day 1 to Day 5.

DRUGMEDI8852

MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.

DRUGPlacebo

Placebo is salt-water solution containing no active ingredients and administered as a single IV infusion on Day 1.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Any Solicited Influenza Symptoms From Day 1 Through Day 10	Day 1 (post-dose) through Day 10	Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).
Number of Participants With Any Solicited Influenza Symptoms From Day 10 Through Day 13	Day 10 through Day 13	Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Day 1 (post-dose) through Day 28	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.
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs)	Day 1 (post-dose) through Day 101	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.
Number of Participants With Treatment Emergent Adverse Events of Special Interest (TEAESIs)	Day 1 (post-dose) through Day 101	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.

Secondary

Measure	Time frame	Description
Percentage of Participants With Influenza Viral Shedding as Measured by Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR)	Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13	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.
Percentage of Participants With Virus Containing Known Oseltamivir Resistance-Associated Mutations	From Baseline (Day 1) to Day 13	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.
Quantitation of Influenza Viral Shedding as Measured by qRT-PCR	Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13	qRT-PCR was used to measure influenza viral shedding from the nasopharyngeal swabs.
Number of Days of Influenza Viral Shedding as Measured by qRT-PCR	From Baseline (Day 1) to Day 7; and Day 9 to Day 13	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.
Percentage of Participants With Amino Acid Changes in MEDI8852 Binding Site	From Baseline (Day 1) to Day 13	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.
Number of Participants With Viral Susceptibility to MEDI8852 as Determined by a Cell Based Microneutralization Assay	From Baseline (Day 1) to Day 13	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.

Countries

South Africa, United States

Participant flow

Recruitment details

The study was conducted from 07 Dec 2015 to 09 Dec 2016 in Australia, South Africa and United States of America.

Pre-assignment details

A total of 373 participants were screened, of which 247 participants were screen failures and 126 participants were randomized in the study.

Participants by arm

Arm	Count
Placebo + Oseltamivir 75 mg Participants received 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.	32
MEDI8852 750 mg + Oseltamivir 75 mg Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	31
MEDI8852 3000 mg + Oseltamivir 75 mg Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	31
MEDI8852 3000 mg Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.	32
Total	126

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Received oseltamivir by error	0	0	0	1
Overall Study	Withdrawal by Subject	1	0	0	0

Baseline characteristics

Characteristic	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg	Total
Age, Continuous	42.3 Years STANDARD_DEVIATION 11.97	40.5 Years STANDARD_DEVIATION 11.97	41.7 Years STANDARD_DEVIATION 12.9	44.3 Years STANDARD_DEVIATION 13.96	42.2 Years STANDARD_DEVIATION 12.66
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants	17 Participants	20 Participants	17 Participants	70 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants	14 Participants	11 Participants	15 Participants	56 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Black or African American	5 Participants	8 Participants	3 Participants	5 Participants	21 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	26 Participants	23 Participants	28 Participants	27 Participants	104 Participants
Sex: Female, Male Female	20 Participants	13 Participants	18 Participants	15 Participants	66 Participants
Sex: Female, Male Male	12 Participants	18 Participants	13 Participants	17 Participants	60 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 32	0 / 31	0 / 31	0 / 31
other Total, other adverse events	9 / 32	11 / 31	15 / 31	12 / 31
serious Total, serious adverse events	1 / 32	0 / 31	1 / 31	0 / 31

Outcome results

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).

Time frame: Day 10 through Day 13