Brief Summary
Influenza (the flu) is a common illness that usually occurs in autumn and winter. The flu is usually mild, but can cause serious illness or death. The purpose of this study is to test the safety and effectiveness of an antibody against the flu (called intravenous hyperimmune immunoglobulin or IVIG) in people who are hospitalized for severe flu.
Brief Title
Evaluating the Safety and Efficacy of Anti-Influenza Intravenous Hyperimmune Immunoglobulin (IVIG) in Adults Hospitalized With Influenza
Detailed Description
Influenza is responsible for thousands of hospitalizations and deaths each year in the United States and worldwide. One possible new treatment for the flu involves the use of IVIG, a blood product containing antibodies from people who have recovered from the flu or who have had a flu shot. The purpose of this study is to evaluate whether IVIG can reduce the severity and duration of flu in people who are hospitalized with the flu.
The study will enroll participants 18 years and older who are hospitalized with the flu. The study will enroll participants over one or more flu seasons. Regardless of the date of enrollment, each participant will be in the study for about 28 days.
At study entry (Day 0), participants will be randomly assigned to one of two groups (Arms A and B). Participants in both groups will receive standard of care (SOC) treatment for the flu, but those in Arm A will also receive one dose of IVIG and those in Arm B will receive a placebo for IVIG. Both IVIG and placebo will be given intravenously over at least 2 hours.
On Day 0, before receiving IVIG or placebo, participants will undergo a symptoms assessment, blood collection, and a nasopharyngeal (NP) swab to collect a sample of secretions from the nose and throat.
Additional study visits will occur on Days 1, 2, 3, 7, 14, and 28. Depending on the visit, participants may take part in the same study procedures that took place on Day 0. On Days 2, 14, and 28, visits for participants who are no longer hospitalized may be conducted over the phone.
The study will enroll participants 18 years and older who are hospitalized with the flu. The study will enroll participants over one or more flu seasons. Regardless of the date of enrollment, each participant will be in the study for about 28 days.
At study entry (Day 0), participants will be randomly assigned to one of two groups (Arms A and B). Participants in both groups will receive standard of care (SOC) treatment for the flu, but those in Arm A will also receive one dose of IVIG and those in Arm B will receive a placebo for IVIG. Both IVIG and placebo will be given intravenously over at least 2 hours.
On Day 0, before receiving IVIG or placebo, participants will undergo a symptoms assessment, blood collection, and a nasopharyngeal (NP) swab to collect a sample of secretions from the nose and throat.
Additional study visits will occur on Days 1, 2, 3, 7, 14, and 28. Depending on the visit, participants may take part in the same study procedures that took place on Day 0. On Days 2, 14, and 28, visits for participants who are no longer hospitalized may be conducted over the phone.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Influenza A
Influenza B
Eligibility Criteria
Inclusion Criteria:
* Signed informed consent
* Locally determined positive influenza test (by polymerase chain reaction \[PCR\] or other nucleic acid test, or by rapid antigen \[Ag\]) from a specimen obtained within 2 days prior to randomization
* Onset of illness no more than 7 days before randomization, defined as when the participant first experienced at least one respiratory symptom or fever
* Hospitalized (or in observation unit) for influenza, with anticipated hospitalization for more than 24 hours. Criteria for hospitalization will be up to the individual treating clinician.
* For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least one form of hormonal or barrier contraception through Day 28 of the study
* Willingness to have blood and respiratory samples obtained and stored
* NEW score greater than or equal to 2 at screening (see the protocol for more information on this criterion)
Exclusion Criteria:
* Women who are pregnant or breast-feeding
* Strong clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily bacterial in origin
* Prior treatment with any investigational drug therapy within 30 days prior to screening
* History of allergic reaction to blood or plasma products (as judged by the site investigator)
* Known immunoglobulin A (IgA) deficiency
* A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the participant at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy)
* Presence of any pre-existing illness that, in the opinion of the site investigator, would place the participant at an unreasonably increased risk through participation in this study
* Participants who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol
* Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the participant (e.g., decompensated congestive heart failure)
* Receiving extracorporeal membrane oxygenation (ECMO)
* Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)
* Signed informed consent
* Locally determined positive influenza test (by polymerase chain reaction \[PCR\] or other nucleic acid test, or by rapid antigen \[Ag\]) from a specimen obtained within 2 days prior to randomization
* Onset of illness no more than 7 days before randomization, defined as when the participant first experienced at least one respiratory symptom or fever
* Hospitalized (or in observation unit) for influenza, with anticipated hospitalization for more than 24 hours. Criteria for hospitalization will be up to the individual treating clinician.
* For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least one form of hormonal or barrier contraception through Day 28 of the study
* Willingness to have blood and respiratory samples obtained and stored
* NEW score greater than or equal to 2 at screening (see the protocol for more information on this criterion)
Exclusion Criteria:
* Women who are pregnant or breast-feeding
* Strong clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily bacterial in origin
* Prior treatment with any investigational drug therapy within 30 days prior to screening
* History of allergic reaction to blood or plasma products (as judged by the site investigator)
* Known immunoglobulin A (IgA) deficiency
* A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the participant at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy)
* Presence of any pre-existing illness that, in the opinion of the site investigator, would place the participant at an unreasonably increased risk through participation in this study
* Participants who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol
* Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the participant (e.g., decompensated congestive heart failure)
* Receiving extracorporeal membrane oxygenation (ECMO)
* Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)
Inclusion Criteria
Inclusion Criteria:
* Signed informed consent
* Locally determined positive influenza test (by polymerase chain reaction \[PCR\] or other nucleic acid test, or by rapid antigen \[Ag\]) from a specimen obtained within 2 days prior to randomization
* Onset of illness no more than 7 days before randomization, defined as when the participant first experienced at least one respiratory symptom or fever
* Hospitalized (or in observation unit) for influenza, with anticipated hospitalization for more than 24 hours. Criteria for hospitalization will be up to the individual treating clinician.
* For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least one form of hormonal or barrier contraception through Day 28 of the study
* Willingness to have blood and respiratory samples obtained and stored
* NEW score greater than or equal to 2 at screening (see the protocol for more information on this criterion)
* Signed informed consent
* Locally determined positive influenza test (by polymerase chain reaction \[PCR\] or other nucleic acid test, or by rapid antigen \[Ag\]) from a specimen obtained within 2 days prior to randomization
* Onset of illness no more than 7 days before randomization, defined as when the participant first experienced at least one respiratory symptom or fever
* Hospitalized (or in observation unit) for influenza, with anticipated hospitalization for more than 24 hours. Criteria for hospitalization will be up to the individual treating clinician.
* For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least one form of hormonal or barrier contraception through Day 28 of the study
* Willingness to have blood and respiratory samples obtained and stored
* NEW score greater than or equal to 2 at screening (see the protocol for more information on this criterion)
Gender
All
Gender Based
false
Keywords
Antiviral
IVIG
Hemagglutination inhibition (HAI)
Antibody
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02287467
Org Class
Nih
Org Full Name
National Institute of Allergy and Infectious Diseases (NIAID)
Org Study Id
INSIGHT 006: FLU-IVIG
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Anti-Influenza Hyperimmune Intravenous Immunoglobulin Clinical Outcome Study (INSIGHT 006: FLU-IVIG)
Primary Outcomes
Outcome Description
This is the primary outcome, a 6-category ordinal outcome ranging from death (worst) to discharged from hospital with resumption of normal activities (best).
Outcome Measure
Number of Patients in Each of 6 Clinical Status Categories on Day 7
Outcome Time Frame
Assessed on Day 7
Secondary Outcomes
Outcome Description
5-category ordinal outcome assessed on day 3; clinical status ranges from death (worst) to discharged from the hospital (best).
Outcome Time Frame
Assessed on Day 3
Outcome Measure
Number of Patients in Each of 5 Clinical Status Categories on Day 3
Outcome Description
6-category ordinal outcome evaluated on Day 3; clinical status ranges from death (worst) to discharged from hospital with resumption of normal activities (best).
Outcome Time Frame
Measured on Day 3
Outcome Measure
Number of Patients in Each of 6 Clinical Status Categories on Day 3
Outcome Description
Sliding dichotomy defined as non-ICU hospitalization or discharge if enrolled from ICU, and discharge if enrolled from the general ward.
Outcome Time Frame
Assessed on Day 7
Outcome Measure
Number of Patients With a Favorable Outcome on Day 7
Outcome Description
Number of participants alive and discharged from the hospital
Outcome Time Frame
Measured through Day 7
Outcome Measure
Hospital Discharge
Outcome Description
Number of participants dying through day 28.
Outcome Time Frame
Measured through day 28
Outcome Measure
Mortality
Outcome Description
Number and percent alive and out of hospital on day 28
Outcome Time Frame
Measured through Day 28
Outcome Measure
Number of Patients Alive and Out of Hospital
Outcome Description
Change in nasopharyngeal viral load from baseline to day 3
Outcome Time Frame
Day 3
Outcome Measure
Change in Viral Load
Outcome Description
Number and percent of participants who died or were re-hospitalized after initial discharge
Outcome Time Frame
Day 28
Outcome Measure
Death or Re-hospitalization
Outcome Description
Number and percent of participants developing respiratory distress syndrome, acute renal failure, sepsis, pneumonia, enteritis, or bronchitis
Outcome Time Frame
Measured through Day 28
Outcome Measure
Percent of Participants Developing Complications
Outcome Description
6-category ordinal outcome measured on day 14
Outcome Time Frame
Measured on day 14
Outcome Measure
Number of Patients in Each of 6 Clinical Status Categories on Day 14
Outcome Description
Number and percentage of participants alive and out of the hospital on Day 14
Outcome Time Frame
day 14
Outcome Measure
Number of Patients Alive and Out of Hospital on Day 14
Outcome Description
Participants reporting resumption of normal daily activities by Day 14
Outcome Time Frame
day 14
Outcome Measure
Resumption of Normal Activities by Day 14
Outcome Description
6-category ordinal outcome corresponding to clinical status on day 28
Outcome Time Frame
day 28
Outcome Measure
Number of Patients in Each of 6 Clinical Status Categories on Day 28
Outcome Description
Primary 6-category ordinal outcome for participants infected with Influenza A
Outcome Time Frame
Day 7
Outcome Measure
Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7
Outcome Description
Primary 6-category ordinal outcome for subgroup of participants infected with influenza B
Outcome Time Frame
Day 7
Outcome Measure
Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7
Outcome Description
pH1N1 hemagglutination inhibition assay (HAI) titers among participants infected with pH1N1 using A/Cal/2009 as reference virus
Outcome Time Frame
Day 7
Outcome Measure
pH1N1 Titers at Day 7
Outcome Description
H3N2 HAI titers among participants infected with H3N2 using A/HongKong/2014 as reference virus
Outcome Time Frame
Day 7
Outcome Measure
H3N2 Titers at Day 7
Outcome Description
Flu B HAI titers among participants infected with influenza B using B/Phuket/2013 as reference virus
Outcome Time Frame
Day 7
Outcome Measure
Influenza B Titers at Day 7
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Paul Riska
Investigator Email
priska@montefiore.org
Investigator Phone
718-020-6494
MeSH Terms
COUNTERFEIT DRUGS
IMMUNOGLOBULINS, INTRAVENOUS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS
IMMUNOGLOBULIN G
IMMUNOGLOBULIN ISOTYPES
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS