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
  Purpose

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.


Condition Intervention Phase
Influenza A
Biological: Anti-Influenza Plasma
Behavioral: Standard Care
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 150
Study Start Date: December 2010
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anti-Influenza Plasma and Standard Care
Participants will receive plasma with high titer anti-influenza A antibodies and standard care.
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
Active Comparator: Standard Care
Participants will receive standard care.
Behavioral: Standard Care
Standard care for hospitalized people with influenza A

Detailed Description:

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).

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01052480

Contacts
Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov
Contact: TTY 1-866-411-1010

  Show 30 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: John Beigel, MD Laboratory of Immunoregulation, NIAID, NIH
Study Chair: Richard Davey, MD Laboratory of Immunoregulation, NIAID, NIH
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01052480     History of Changes
Other Study ID Numbers: 10-I-0043, IRC002
Study First Received: January 16, 2010
Last Updated: August 18, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Antiviral
H1N1 Plasma
Infectious Disease
Swine Flu

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 30, 2014