Safety and Efficacy of Investigational Anti-Influenza Immune Plasma in Treating Influenza

Influenza A Clinical Trial

— IRC002  

Official title:

A Randomized, Open-Label, Phase 2, Multicenter Safety and Exploratory Efficacy Study of Investigational Anti-Influenza Immune Plasma for the Treatment of Influenza (IRC002)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01052480
• Other study ID #: 10-I-0043
• Secondary ID: IRC002
• Status: Completed
• Phase: Phase 2
• First received: January 16, 2010
• Last updated: August 12, 2016
• Start date: December 2010
• Est. completion date: November 2015

Study information

• Verified date: August 2016
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized, open-label, multicenter phase 2 trial will assess the safety, efficacy, and pharmacokinetics (PK) of anti-influenza plasma in subjects with influenza A or B. Hospitalized subjects with influenza A or B that have either a low oxygen level or a high respiratory rate will be eligible for study participation. This study will enroll adults, children and pregnant women.

Description:

Morbidity and mortality occur despite treatment with current antivirals. Circulating influenza H1N1 and H3N2 isolates are highly resistant to amantadine and rimantadine, whereas previous seasonal H1N1 isolates were highly resistant to oseltamivir. So there is concern that circulating influenza A/H1N1 2009 virus may also acquire oseltamivir resistance.

This randomized, open-label, multicenter phase 2 trial will assess the safety, efficacy, and pharmacokinetics (PK) of anti-influenza plasma in subjects with influenza. Hospitalized subjects with influenza at risk for severe disease (as defined in the inclusion criteria) will be eligible for study participation. This study will enroll adults, children and pregnant women.

Up to 40 sites in the United States will participate in this protocol. One hundred eligible subjects will be randomized in a 1:1 ratio to receive either 2 units (or pediatric equivalent) of anti-influenza immune plasma on Study Day 0 in addition to standard care or standard care alone (50 subjects receiving standard care alone; 50 subjects receiving anti-influenza immune plasma and standard care).

Subjects will be assessed on Study Day 0 (pre-dose), 30 minutes post-dose (plasma arm only), and on Study Days 1, 2, 4, 7, 14, and 28. All subjects will undergo a series of efficacy, safety, and PK (HAI) assessments during the study. Blood samples will be collected at each time point (except Day 1). Nasal and oropharyngeal swabs for influenza PCR will be obtained on Days 0,1,2,4 and 7.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: November 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Diagnosis of influenza A or B prior to enrollment

• Hospitalization for signs and symptoms of influenza (decision for hospitalization will be up to the individual treating clinician).

• Abnormal respiratory status, defined as room air saturation of oxygen (SaO2) less than 93% or tachypnea (respiratory rate above normal)

• Agree to the storage of specimens and data

• ABO compatible plasma available on site or available within 24 hours after randomization with activity against locally circulating strains of influenza

Exclusion Criteria:

• Receipt of non-licensed treatment for influenza within the last 2 weeks (or plans to receive any time during the study). This does not include licensed drugs at nonapproved doses, off-label indications, or drugs available under an Emergency Use Authorization (EUA).

• Symptoms or signs of the acute influenza-like illness have occurred for more than 7 days prior to enrollment.

• History of severe allergic reaction to blood products (as judged by the investigator).

• Medical conditions for which receipt of 500 mL volume (or 8 mL/kg for pediatric patients) may be dangerous to the subject (e.g. decompensated congestive heart failure [CHF], etc.)

• Clinical suspicion that etiology of illness is primarily bacterial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Influenza A
• Influenza B
• Influenza, Human

Intervention

Biological:
• Anti-Influenza Immune Plasma
2 units of plasma with high titer anti-influenza A or anti-influenza B antibodies at baseline

Behavioral:
• Standard Care
Standard care for hospitalized people with influenza

Locations

Country	Name	City	State
United States	Texas Tech University Health Science Center (HSC)- Amarillo	Amarillo	Texas
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	John Hopkins University (JHU)	Baltimore	Maryland
United States	University of Maryland School of Medicine Center for Vaccine Development	Baltimore	Maryland
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland
United States	Walter Reed National Military Medical Center (WRNMMC)	Bethesda	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Med Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Brigham and Women's Hospital/Harvard Medical School	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University (NU)	Chicago	Illinois
United States	The Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati College of Medicine	Cincinnati	Ohio
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	University of Florida	Gainesville	Florida
United States	Texas Children's Hospital	Houston	Texas
United States	Bronson Healthcare Group	Kalamazoo	Michigan
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Texas Tech HSC-Lubbock, TX	Lubbock	Texas
United States	Cornell Clinical Trials Unit, New York Presbyterian Hospital, Weill Cornell Medical College	New York	New York
United States	Montefiore Medical Center/Albert Einstein College of Medicine	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Hospital of the University of Pennsylvania	Philadephia	Pennsylvania
United States	University of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania
United States	Naval Medical Center Portsmouth	Portsmouth	Virginia
United States	Saint Mary's Hospital (Mayo Clinic)	Rochester	Minnesota
United States	Naval Medical Center San Diego	San Diego	California
United States	Madigan Army Medical Center (MAMC)	Tacoma	Washington
United States	Los Angeles Biomedical Research Institute, CA	Torrance	California
United States	Children's National Medical Center	Washington	District of Columbia
United States	Washington, DC VA Med Center	Washington	District of Columbia
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Bean WJ, Schell M, Katz J, Kawaoka Y, Naeve C, Gorman O, Webster RG. Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts. J Virol. 1992 Feb;66(2):1129-38. — View Citation

de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, Bach VC, Phan TQ, Do QH, Guan Y, Peiris JS, Tran TH, Farrar J. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005 Dec 22;353(25):2667-72. — View Citation

Morse SS. Factors in the emergence of infectious diseases. Emerg Infect Dis. 1995 Jan-Mar;1(1):7-15. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to normalization of respiratory status (defined as room air saturation of oxygen [SaO2] greater than or equal to 93% AND respiratory rate within normal ranges)		Measured at Day 28	Yes
Secondary	Duration of clinical symptoms, fever, intensive care unit (ICU) stay, and hospitalization		Measured at Day 28	Yes
Secondary	Time to resolution of symptoms and fever		Measured at Day 28	Yes
Secondary	Mortality		Measured at Day 28	Yes
Secondary	Acute lung injury		Measured at Day 28	Yes
Secondary	Acute respiratory distress syndrome (ARDS)		Measured at Day 28	Yes
Secondary	Time to 20% improvement in sequential organ failure assessment (SOFA) score for participants at least 18 years old and pediatric logistic organ dysfunction (PELOD) score for those younger than 18 years old		Measured at study completion	Yes
Secondary	Time to 50 millimeters of mercury (mm/Hg) improvement in partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio		Measured at study completion	No
Secondary	Incidence and duration of both supplemental oxygen use and mechanical ventilation use		Measured at Day 28	Yes
Secondary	Disposition following initial hospitalization		Measured at Day 28	Yes
Secondary	Birth complications for pregnant women		Measured at Day 28	Yes
Secondary	Adverse events and laboratory abnormalities		Measured at Day 28	Yes
Secondary	Relationship between hemagglutination inhibition assay (HAI) and measures of viral clearance		Measured at Day 28	No