Safety and Efficacy of Investigational Immune Plasma in Treating Influenza A (IRC002)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01052480
First received: January 16, 2010
Last updated: August 18, 2014
Last verified: August 2014

January 16, 2010
August 18, 2014
December 2010
October 2015   (final data collection date for primary outcome measure)
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) [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
Safety and Efficacy: The time to a 20% improvement in the OD score for age greater than or equal to 18 years, and PLOD score for age less than 18 years from Day 0 score in subjects treated with H1N1 plasma as compared to plasma.
Complete list of historical versions of study NCT01052480 on ClinicalTrials.gov Archive Site
  • Duration of clinical symptoms, fever, intensive care unit (ICU) stay, and hospitalization [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  • Time to resolution of symptoms and fever [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  • Mortality [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  • Acute lung injury [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  • Acute respiratory distress syndrome (ARDS) [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
  • Time to 50 millimeters of mercury (mm/Hg) improvement in partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  • Incidence and duration of both supplemental oxygen use and mechanical ventilation use [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  • Disposition following initial hospitalization [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  • Birth complications for pregnant women [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  • Adverse events and laboratory abnormalities [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: Yes ]
  • Relationship between hemagglutination inhibition assay (HAI) and measures of viral clearance [ Time Frame: Measured at Day 28 ] [ Designated as safety issue: No ]
Duration of clinical symptoms, fever, ICU stay and hospitalization. Time to resolution of symptoms and fever. Mortality.
Not Provided
Not Provided
 
Safety and Efficacy of Investigational Immune Plasma in Treating Influenza A
A Randomized, Open-Label, Phase 2, Multicenter Safety and Exploratory Efficacy Study of Investigational Anti-Influenza A Immune Plasma for the Treatment of Influenza A (IRC002)

Influenza A/H1N1 2009 (commonly referred to as "swine flu") is a novel influenza virus. Severe morbidity and mortality occur despite treatment with current antivirals. H1N1 vaccines are available, but much of the population remains unvaccinated. Of most concern, are 2 types of influenza A that widely circulate in humans and cause seasonal outbreaks and epidemics - H1N1 and H3N2. This randomized, open-label, multi-center, Phase 2 trial will assess the safety, efficacy, and pharmacokinetics of anti-influenza plasma in participants with influenza A (H1N1, H3N2). Hospitalized participants with influenza A at risk of severe disease (as defined in the inclusion criteria) will be eligible for study participation. This study will enroll adults, children and pregnant women.

Influenza A/H1N1 2009 (also referred to as "swine flu") is a novel influenza virus. H1N1 vaccines are available, but much of the population remains unvaccinated. Initial reports suggested a high mortality rate (6-7%). More recent statistics suggest a much lower mortality rate similar to seasonal influenza, though in contrast to seasonal influenza, influenza A/H1N1 2009 affects a younger, healthier population.

Morbidity and mortality occur despite treatment with current antivirals. Circulating influenza A/H1N1 2009 isolates are highly resistant to amantadine and rimantadine, whereas previous seasonal H1N1 isolates were highly resistant to oseltamivir. So there is concern that the 2009 H1N1 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 A. Hospitalized subjects with influenza A 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.

Approximately 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 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 plasma and standard care).

Subjects will be assessed on Study Day 0 (pre-dose), 30 minutes post-dose, 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).

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Influenza A
  • Biological: Anti-Influenza Plasma
    2 units of plasma with high titer anti-influenza A antibodies at baseline
  • Behavioral: Standard Care
    Standard care for hospitalized people with influenza A
  • Experimental: Anti-Influenza Plasma and Standard Care
    Participants will receive plasma with high titer anti-influenza A antibodies and standard care.
    Interventions:
    • Biological: Anti-Influenza Plasma
    • Behavioral: Standard Care
  • Active Comparator: Standard Care
    Participants will receive standard care.
    Intervention: Behavioral: Standard Care

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
150
Not Provided
October 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of influenza A (confirmed by local assay that may test for either influenza A or more specific influenza A H1N1 2009, including rapid antigen, direct fluorescent antibody [DFA], polymerase chain reaction [PCR], or culture)
  • 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
  • Agree to the storage of specimens and data
  • ABO compatible H1N1 plasma available

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
Both
Not Provided
No
Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov
Contact: TTY 1-866-411-1010
United States
 
NCT01052480
10-I-0043, IRC002
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: John Beigel, MD Laboratory of Immunoregulation, NIAID, NIH
Study Chair: Richard Davey, MD Laboratory of Immunoregulation, NIAID, NIH
National Institute of Allergy and Infectious Diseases (NIAID)
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP