Clinical trial NCT01052480: Safety and Efficacy of Investigational Anti-Influenza Immune Plasma in Treating Influenza
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza A
Influenza B
Keywords: Antiviral
Anti-Influenza Immune Plasma
Emerging Infectious Disease
Swine Flu
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2010-01-20
Enrollment: 98
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of influenza A or B within 72 hours prior to enrollment (by local assay including rapid antigen, direct fluorescent antibody (DFA), polymerase chain reaction (PCR), or culture, and must be able to detect and distinguish influenza A from influenza B)
* 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 an age adjusted normal range)
* 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 non approved doses, off-label indications, or drugs available under an Emergency Use Authorization (EUA).
* 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 acute illness is primarily due to a condition other than active influenza virus replication (e.g., a bacterial or fungal infection)

Primary outcomes:
measure: Time to Normalization of Respiratory Status (Primary Efficacy Population)
timeFrame: Measured from Day 0 through Day 28
Secondary outcomes:
measure: Time to Normalization of Respiratory Status (All Randomized Participants)
timeFrame: Measured from Day 0 through Day 28
measure: Duration of Time to Resolution of Clinical Symptoms
timeFrame: Measured from Day 0 through Day 28
measure: Duration of Time to Resolution of Fever
timeFrame: Measured from Day 0 through Day 28
measure: Duration of Time to Resolution of All Symptoms and Fever
timeFrame: Measured from Day 0 through Day 28
measure: Time to 20% Improvement in Sequential Organ Failure Assessment (SOFA) Score for Participants >= 18 Years Old and Pediatric Logistic Organ Dysfunction (PELOD) Score for Participants < 18 Years Old
timeFrame: Measured from Day 0 through Day 28
measure: 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time
timeFrame: Measured at Days 1, 2, 4, 7, 14, 28
measure: In-hospital Mortality
timeFrame: Measured from Day 0 through Day 28
measure: 28-day Mortality
timeFrame: Measured from Day 0 through Day 28
measure: Duration of Hospitalization
timeFrame: Measured from Day 0 through Day 28
measure: Number of ICU Admissions
timeFrame: Measured from Day 0 through Day 28
measure: Duration of Stay in ICU
timeFrame: Measured from Day 0 through Day 28
measure: Days on Supplemental Oxygen
timeFrame: Measured from Day 0 through Day 28
measure: Duration of Supplemental Oxygen
timeFrame: Measured from Day 0 through Day 28
measure: Incidence of Acute Respiratory Distress Syndrome (ARDS) Present
timeFrame: Measured at Days 0, 1, 2, 4, 7, 14, 28
measure: Days on Mechanical Ventilation
timeFrame: Measured from Day 0 through Day 28
measure: Duration of Mechanical Ventilation
timeFrame: Measured from Day 0 through Day 28
measure: Disposition Following Initial Hospitalization
timeFrame: Measured from Day 0 through Day 28
measure: Duration of Viral Shedding < Lower Limit of Quantification (LLOQ) in Nasal Swabs
timeFrame: Measured from Day 0 through Day 28
measure: Incidence and Week of Gestation of Delivery of a Live Pre-term Infant for Pregnant Women
timeFrame: Measured through to Day 28
measure: Incidence and Duration of Pre-term Labor (Defined as Labor Occurring < 36 Weeks) for Pregnant Women
timeFrame: Measured through Day 28
measure: Incidence of Spontaneous Abortion or Stillborn Fetus for Pregnant Women
timeFrame: Measured from Day 0 through Day 28
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: San Diego
country: United States
facility: Naval Medical Center San Diego
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute, CA
state: California
city: Washington, D.C.
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Washington, D.C.
country: United States
facility: Washington, DC VA Med Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University (NU)
state: Illinois
city: Chicago
country: United States
facility: The Rush University Medical Center
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland School of Medicine Center for Vaccine Development
state: Maryland
city: Baltimore
country: United States
facility: John Hopkins University (JHU)
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center (WRNMMC)
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital/Harvard Medical School
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Med Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Healthcare Group
state: Michigan
city: Rochester
country: United States
facility: Saint Mary's Hospital (Mayo Clinic)
state: Minnesota
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Cornell Clinical Trials Unit, New York Presbyterian Hospital, Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Montefiore Medical Center/Albert Einstein College of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Amarillo
country: United States
facility: Texas Tech University Health Science Center (HSC)- Amarillo
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Lubbock
country: United States
facility: Texas Tech HSC-Lubbock, TX
state: Texas
city: Portsmouth
country: United States
facility: Naval Medical Center Portsmouth
state: Virginia
city: Tacoma
country: United States
facility: Madigan Army Medical Center (MAMC)
state: Washington
Study officials:
affiliation: Leidos Biomedical Research, Inc. in support of Laboratory of Immunoregulation, NIAID, NIH
name: John Beigel, MD
role: STUDY_CHAIR
affiliation: Laboratory of Immunoregulation, NIAID, NIH
name: Richard Davey, MD
role: STUDY_CHAIR
References:
citation: Morse SS. Factors in the emergence of infectious diseases. Emerg Infect Dis. 1995 Jan-Mar;1(1):7-15. doi: 10.3201/eid0101.950102.
citation: 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. doi: 10.1128/JVI.66.2.1129-1138.1992.
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. doi: 10.1056/NEJMoa054512.
citation: Beigel JH, Tebas P, Elie-Turenne MC, Bajwa E, Bell TE, Cairns CB, Shoham S, Deville JG, Feucht E, Feinberg J, Luke T, Raviprakash K, Danko J, O'Neil D, Metcalf JA, King K, Burgess TH, Aga E, Lane HC, Hughes MD, Davey RT; IRC002 Study Team. Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study. Lancet Respir Med. 2017 Jun;5(6):500-511. doi: 10.1016/S2213-2600(17)30174-1. Epub 2017 May 15.