Exploring Safety & Clinical Benefit of Anti-Influenza Immunoglobulin Intravenous in Hospitalized Adults With Influenza A

NCT03315104 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IA-001
• Study Type: interventional
• Target: 65
• Locations: 4 countries
• Sites: 55

Brief Summary

Influenza, or the flu, is an infectious respiratory disease that can range in severity from mild to severe to even death. This study aims to evaluate a treatment for people who are hospitalized with the flu. The study is looking to see if antibodies collected from people who have recovered from the seasonal flu or who have had the seasonal flu shot can be used safely as a study drug to treat hospitalized patients with severe flu infections. Also, this study will help to find the right dose for this study drug for treatment of severe flu in hospitalized patients. Overall, this study will evaluate if the hospitalized patients receiving standard of care along with the study drug get better more quickly than those treated with standard of care and placebo. The study drug that contains antibodies against the flu is called anti-influenza immunoglobulin intravenous (FLU-IGIV).

Conditions

Influenza A H3N2; Influenza A H1N1

Keywords

influenza A; hospitalized; H1N1; H3N2; human flu; respiratory tract infection; serious illness; flu

Outcome Measures

Primary Outcomes (4)

• Frequency Counts and Percentage of Subjects With Adverse Events

  Frequency counts and percentage of subjects with Adverse Events by severity

  Measured through Day 60

• Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay

  Levels of anti-influenza A antibodies circulating in blood over time. We initially intended to look at this variable through Day 8, however, potential native antibody level changes and sparse sampling confounded results from 0 to 48 hours post-dose from PK samples collected from Baseline Day 1 pre-dose (time 0), Day 1 post-dose, Day 2 and Day 3 (if continued hospitalization), and Day 8. For AUC from time 0 to 48 hours, subjects who did not have a sample collected within +/-10% of 48 hours post-dose had this parameter set to missing, which is why the number of subjects who contributed data for this outcome measure is lower than the overall number of subjects analyzed.

  Measured through 48 Hours post-dose

• Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay

  Maximum observed concentration (reported as a titer) of anti-influenza A antibodies measured from Day 1 pre-dose (time 0) through Day 8 post-dose from PK samples collected from Baseline Day 1 pre-dose (time 0), Day 1 post-dose, Day 2 and Day 3 (if continued hospitalization), and Day 8.

  Measured through Day 8 post-dose

• Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay

  Time that anti-influenza A antibodies are at maximum concentration from Day 1 pre-dose (time 0) through Day 8 post-dose from PK samples collected from Baseline Day 1 pre-dose (time 0), Day 1 post-dose, Day 2 and Day 3 (if continued hospitalization), and Day 8. The rate of study drug elimination and dependent parameters were not accurately estimable due to rising or sustained levels of anti-influenza A antibodies, this includes First Order Terminal Elimination Rate Constant \[Kel\], Plasma Clearance \[Cl\] and Total Volume of Distribution \[Vz\].

  Measured through Day 8 post-dose

Secondary Outcomes (1)

• Ordinal Scale Subject Distribution Reflecting Clinical Status

  At Day 8 post-dose

Study Arms (3)

FLU-IGIV High Dose

EXPERIMENTAL

Participants will receive a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Participants will also receive standard of care (SOC) antiviral treatment for flu. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.

Biological: FLU-IGIV

FLU-IGIV Low Dose

EXPERIMENTAL

Participants will receive a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Participants will also receive SOC antiviral treatment for flu. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.

Biological: FLU-IGIV

FLU-IGIV Placebo

PLACEBO COMPARATOR

Participants will receive a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Participants will also receive SOC antiviral treatment for flu. Administered IV as 500 mL of normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.

Other: Placebo for FLU-IGIV

Interventions

FLU-IGIV BIOLOGICAL

Single dose, sterile liquid formulation for IV administration.

Also known as: Anti-influenza immunoglobulin intravenous (Human), NP-025

FLU-IGIV High Dose; FLU-IGIV Low Dose

Placebo for FLU-IGIV OTHER

Single dose, normal saline solution for IV administration.

FLU-IGIV Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of voluntary informed consent in writing by patient, or legally authorized representative.
• Age ≥ 18 years of age.
• Locally determined positive influenza A infection (Rapid Antigen (Ag) Test or PCR) from a specimen obtained within 2 days prior to randomization.
• Onset of symptoms ≤ 6 days before randomization, defined as when the patient first experienced at least one respiratory symptom or fever.
• Hospitalized (or in observation unit) with influenza, with anticipated hospitalization for more than 24 hours and will be/already are receiving antiviral SOC.
• Experiencing ≥ 1 respiratory symptom (ex. cough, sore throat, nasal congestion) and ≥ 1 constitutional symptom (ex. headache, myalgia, feverishness or fatigue).
• For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least 1 form of hormonal or barrier contraception through Day 60 of the study.
• Willingness to have blood and respiratory samples obtained and stored.
• National Early Warning Score (NEW score) ≥ 3 at screening.

You may not qualify if:

• Use of any investigational product within the past 30 days prior to screening.
• History of hypersensitivity to blood or plasma products (as judged by the site investigator).
• History of allergy to latex or rubber.
• Known medical history of IgA deficiency.
• Pregnancy or lactation.
• Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the patient (e.g. decompensated congestive heart failure), based on investigator's medical opinion with careful consideration of lab results.
• Liver function: liver function test (LFT) \> 2.5 times upper limit of normal (ULN).
• Renal Function: glomerular filtration rate (GFR) \< 60 mL/min/1.73 m2 (age and sex adjusted).
• A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g. cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy).
• Receiving extracorporeal membrane oxygenation (ECMO).
• Anticipated life expectancy of \< 90 days.
• Confirmed bacterial pneumonia or any concurrent respiratory viral infection that is not influenza A (ex. respiratory syncytial virus (RSV) infection).

Sponsors & Collaborators

• Emergent BioSolutions: lead

Study Sites (55)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Baptist Health Center for Clinical Research

Little Rock, Arkansas, 72205, United States

Location

University of California, Irvine Emergency Medicine

Orange, California, 92868, United States

Location

Denver public Health

Denver, Colorado, 80212, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

Location

Christiana Care Health Systems

Newark, Delaware, 19718, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Atlanta Institute for Medical Research Inc.

Atlanta, Georgia, 30350, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas medical Center

Kansas City, Kansas, 66160, United States

Location

John Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01605, United States

Location

Wayne State University/Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Wayne State University/Sinai Grace Hospital

Detroit, Michigan, 48202, United States

Location

Providence-Providence Park Hospital, Southfield

Southfield, Michigan, 48075, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 985400, United States

Location

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Pulmonlx LLC Pulmonary & Critical Care Medicine

Greensboro, North Carolina, 27403, United States

Location

Premier Health Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

St Luke's University Health Network

Bethlehem, Pennsylvania, 18015, United States

Location

Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Regional Health

Rapid City, South Dakota, 57701, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor University Medical Center

Dallas, Texas, 77030, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Michael E. DeBakey VA Medical Center

Houston, Texas, 77030, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah HealthCare

Salt Lake City, Utah, 84108, United States

Location

Carilion Medical Center

Roanoke, Virginia, 24014, United States

Location

MultiCare Institute for Research & Innovation

Tacoma, Washington, 98405, United States

Location

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Health Sciences Center

Winnipeg, Manitoba, R3A 1R9, Canada

Location

St. Boniface Hospital

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Grace Hospital

Winnipeg, Manitoba, R3J 3M7, Canada

Location

CISSS BSL/Hopital Regional de Rimouski

Rimouski, Quebec, G5L 5T1, Canada

Location

Ciusss McQ

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Mayaguez Medical Center

Mayagüez, 00680, Puerto Rico

Location

San Cristobal Hospital

Ponce, 00780, Puerto Rico

Location

Hospital Clinic of Barcelona

Barcelona, 08036, Spain

Location

Hospital del Mar

Barcelona, 08036, Spain

Location

Hospital Universitari Mutua Terrassa

Barcelona, 08225, Spain

Location

Reina Sofia University Hospital

Córdoba, 14004, Spain

Location

Hospital Universitari de Tarragona Joan XXIII

Tarragona, 43007, Spain

Location

MeSH Terms

Conditions

Orthomyxoviridae Infections; Influenza, Human; Respiratory Tract Infections

Condition Hierarchy (Ancestors)

RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases

Limitations and Caveats

This phase 2 study was not powered to show efficacy. The target enrollment of 75 subjects randomized was not met (65 randomized and 60 dosed); the study was completed after the second northern hemisphere influenza season.

Results Point of Contact

• Title: Dr. Christine Hall
• Organization: Emergent BioSolutions

chall@ebsi.com

204-275-4200

Study Officials

• Christine Hall

  Emergent BioSolutions Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Staggered enrollment for the first 9 subjects, then parallel low and high dose treatment with a placebo group

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: October 19, 2017
• Study Start: November 17, 2017
• Primary Completion: June 17, 2019
• Study Completion: June 17, 2019
• Last Updated: March 18, 2024
• Results First Posted: October 5, 2020

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Within 1 year after the study's Primary Completion Date (Last Subject Last Visit).

Locations

US (42); ES (5); CA (6); PR (2)