A Randomized, Open-Label, Phase 2, Multicenter Safety and Exploratory Efficacy Study of Investigational Anti-Influenza Immune Plasma for the Treatment of Influenza (IRC002)
Overview
- Phase
- Phase 2
- Intervention
- Anti-Influenza Immune Plasma
- Conditions
- Influenza A
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 98
- Locations
- 35
- Primary Endpoint
- Time to Normalization of Respiratory Status (Primary Efficacy Population)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
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)
Arms & Interventions
Plasma and Standard Care
Participants will receive plasma with high titer anti-influenza A or anti-influenza B antibodies (Anti-Influenza Immune Plasma) in addition to standard care.
Intervention: Anti-Influenza Immune Plasma
Plasma and Standard Care
Participants will receive plasma with high titer anti-influenza A or anti-influenza B antibodies (Anti-Influenza Immune Plasma) in addition to standard care.
Intervention: Standard Care
Standard Care
Participants will receive standard care.
Intervention: Standard Care
Outcomes
Primary Outcomes
Time to Normalization of Respiratory Status (Primary Efficacy Population)
Time Frame: Measured from Day 0 through Day 28
Normalized respiratory status is defined as room air saturation of oxygen \[SaO2\] greater than or equal to 93% AND respiratory rate within normal ranges.
Secondary Outcomes
- 50 Millimeters of Mercury (mm/Hg) Improvement in PaO2/FiO2 Ratio Over Time(Measured at Days 1, 2, 4, 7, 14, 28)
- Number of ICU Admissions(Measured from Day 0 through Day 28)
- Duration of Stay in ICU(Measured from Day 0 through Day 28)
- 28-day Mortality(Measured from Day 0 through Day 28)
- Duration of Hospitalization(Measured from Day 0 through Day 28)
- Time to Normalization of Respiratory Status (All Randomized Participants)(Measured from Day 0 through Day 28)
- Duration of Time to Resolution of Clinical Symptoms(Measured from Day 0 through Day 28)
- Duration of Time to Resolution of Fever(Measured from Day 0 through Day 28)
- Duration of Time to Resolution of All Symptoms and Fever(Measured from Day 0 through Day 28)
- 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(Measured from Day 0 through Day 28)
- In-hospital Mortality(Measured from Day 0 through Day 28)
- Days on Supplemental Oxygen(Measured from Day 0 through Day 28)
- Duration of Supplemental Oxygen(Measured from Day 0 through Day 28)
- Incidence of Acute Respiratory Distress Syndrome (ARDS) Present(Measured at Days 0, 1, 2, 4, 7, 14, 28)
- Days on Mechanical Ventilation(Measured from Day 0 through Day 28)
- Duration of Mechanical Ventilation(Measured from Day 0 through Day 28)
- Disposition Following Initial Hospitalization(Measured from Day 0 through Day 28)
- Duration of Viral Shedding < Lower Limit of Quantification (LLOQ) in Nasal Swabs(Measured from Day 0 through Day 28)
- Incidence and Week of Gestation of Delivery of a Live Pre-term Infant for Pregnant Women(Measured through to Day 28)
- Incidence and Duration of Pre-term Labor (Defined as Labor Occurring < 36 Weeks) for Pregnant Women(Measured through Day 28)
- Incidence of Spontaneous Abortion or Stillborn Fetus for Pregnant Women(Measured from Day 0 through Day 28)