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

Influenza A H1N1 Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled Dose Ranging Study Evaluating Safety, Pharmacokinetics and Clinical Benefit of FLU-IGIV in Hospitalized Patients With Serious Influenza A Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03315104
• Other study ID #: IA-001
• Status: Completed
• Phase: Phase 2
• Start date: November 17, 2017
• Est. completion date: June 17, 2019

Study information

• Verified date: March 2024
• Source: Emergent BioSolutions
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: June 17, 2019
• Est. primary completion date: June 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

• An opinion of the investigator that it would be unwise to allow participation of the patient in the study (the reason for exclusion of the patient must be documented).

• 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).

Related Conditions & MeSH terms

• Influenza A H1N1
• Influenza A H3N2
• Influenza, Human

Intervention

Biological:
• FLU-IGIV
Single dose, sterile liquid formulation for IV administration.

Other:
• Placebo for FLU-IGIV
Single dose, normal saline solution for IV administration.

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	CISSS BSL/Hopital Regional de Rimouski	Rimouski	Quebec
Canada	Ciusss McQ	Trois-Rivières	Quebec
Canada	Grace Hospital	Winnipeg	Manitoba
Canada	Health Sciences Center	Winnipeg	Manitoba
Canada	St. Boniface Hospital	Winnipeg	Manitoba
Puerto Rico	Mayaguez Medical Center	Mayagüez
Puerto Rico	San Cristobal Hospital	Ponce
Spain	Hospital Clinic of Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Mutua Terrassa	Barcelona
Spain	Reina Sofia University Hospital	Córdoba
Spain	Hospital Universitari de Tarragona Joan XXIII	Tarragona
United States	Atlanta Institute for Medical Research Inc.	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Augusta University	Augusta	Georgia
United States	John Hopkins Hospital	Baltimore	Maryland
United States	St Luke's University Health Network	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Baylor University Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Premier Health Miami Valley Hospital	Dayton	Ohio
United States	Denver public Health	Denver	Colorado
United States	Wayne State University/Detroit Receiving Hospital	Detroit	Michigan
United States	Wayne State University/Sinai Grace Hospital	Detroit	Michigan
United States	Pulmonlx LLC Pulmonary & Critical Care Medicine	Greensboro	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Michael E. DeBakey VA Medical Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Kansas medical Center	Kansas City	Kansas
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Baptist Health Center for Clinical Research	Little Rock	Arkansas
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Christiana Care Health Systems	Newark	Delaware
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of California, Irvine Emergency Medicine	Orange	California
United States	Einstein Medical Center	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Regional Health	Rapid City	South Dakota
United States	Carilion Medical Center	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	University of Utah HealthCare	Salt Lake City	Utah
United States	UT Health San Antonio	San Antonio	Texas
United States	HonorHealth	Scottsdale	Arizona
United States	Providence-Providence Park Hospital, Southfield	Southfield	Michigan
United States	MultiCare Institute for Research & Innovation	Tacoma	Washington
United States	Reading Hospital	West Reading	Pennsylvania
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Emergent BioSolutions

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency Counts and Percentage of Subjects With Adverse Events	Frequency counts and percentage of subjects with Adverse Events by severity	Measured through Day 60
Primary	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
Primary	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
Primary	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	Ordinal Scale Subject Distribution Reflecting Clinical Status	Score (physician-assessed): 1=death; 2=hospitalization in the intensive care unit (ICU); 3=non-ICU hospitalization requiring supplemental oxygen; 4=non-ICU hospitalization not requiring supplemental oxygen; 5=no longer hospitalized but unable to resume normal activities; 6=no longer hospitalized with full resumption of normal activities. A higher score reflects improved clinical status. Not all ITT subjects had ordinal scale data available at Day 8 post-dose which explains why the overall number of participants analyzed is not consistent with the overall number of subjects included at baseline. For subjects who were discharged with unknown ordinal score the more conservative of two relevant discharged categories was imputed.	At Day 8 post-dose