Title
Evaluating the Safety and Efficacy of Anti-Influenza Intravenous Hyperimmune Immunoglobulin (IVIG) in Adults Hospitalized With Influenza
Anti-Influenza Hyperimmune Intravenous Immunoglobulin Clinical Outcome Study (INSIGHT 006: FLU-IVIG)
Phase
Phase 3Study Type
InterventionalStatus
Completed Results PostedIndication/Condition
Influenza A Influenza BIntervention/Treatment
immune globulin (human) ...Study Participants
329Influenza (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.
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.
Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
Administered IV as 500 mL of normal saline
Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.
Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.
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)
| Event Type | Organ System | Event Term | Arm A: hIVIG | Arm B: Placebo |
|---|
This is the primary outcome, a 6-category ordinal outcome ranging from death (worst) to discharged from hospital with resumption of normal activities (best).
5-category ordinal outcome assessed on day 3; clinical status ranges from death (worst) to discharged from the hospital (best).
6-category ordinal outcome evaluated on Day 3; clinical status ranges from death (worst) to discharged from hospital with resumption of normal activities (best).
Sliding dichotomy defined as non-ICU hospitalization or discharge if enrolled from ICU, and discharge if enrolled from the general ward.
Number of participants alive and discharged from the hospital
Number of participants dying through day 28.
Number and percent alive and out of hospital on day 28
Change in nasopharyngeal viral load from baseline to day 3
Number and percent of participants who died or were re-hospitalized after initial discharge
Number and percent of participants developing respiratory distress syndrome, acute renal failure, sepsis, pneumonia, enteritis, or bronchitis
6-category ordinal outcome measured on day 14
Number and percentage of participants alive and out of the hospital on Day 14
Participants reporting resumption of normal daily activities by Day 14
6-category ordinal outcome corresponding to clinical status on day 28
Primary 6-category ordinal outcome for participants infected with Influenza A
Primary 6-category ordinal outcome for subgroup of participants infected with influenza B
pH1N1 hemagglutination inhibition assay (HAI) titers among participants infected with pH1N1 using A/Cal/2009 as reference virus
H3N2 HAI titers among participants infected with H3N2 using A/HongKong/2014 as reference virus
Flu B HAI titers among participants infected with influenza B using B/Phuket/2013 as reference virus
