Anti-Influenza Hyperimmune Intravenous Immunoglobulin Pilot Study (INSIGHT 005: Flu-IVIG Pilot)

Influenza Clinical Trial

Official title:

Anti-Influenza Hyperimmune Intravenous Immunoglobulin Pilot Study (INSIGHT 005: Flu-IVIG Pilot)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02008578
• Other study ID #: 14-I-0031
• Secondary ID: 14-I-0031
• Status: Completed
• Phase: Phase 1
• First received: December 6, 2013
• Last updated: August 12, 2016
• Start date: December 2013
• Est. completion date: June 2014

Study information

• Verified date: August 2016
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this randomized, double-blind, placebo-controlled trial of intravenous hyperimmune immunoglobulin (Flu-IVIG) in individuals with influenza A or B is to determine the pharmacokinetic (PK) profile of Flu-IVIG and assess whether antibody levels observed following Flu-IVIG transfusion are similar to those predicted. This pilot study will inform a larger study that will be powered to compare Flu-IVIG with placebo for efficacy.

Description:

The purpose of this randomized, double-blind, placebo-controlled trial of intravenous hyperimmune immunoglobulin (Flu-IVIG) in individuals with influenza A or B is to determine the pharmacokinetic (PK) profile of Flu-IVIG and assess whether antibody levels observed following Flu-IVIG transfusion are similar to those predicted. This pilot study will inform a larger study that will be powered to compare Flu-IVIG with placebo for efficacy. In addition to informing the Flu-IVIG dosing required for the clinical outcomes trial, the pilot study will compare influenza antibody levels and safety for study participants randomly assigned Flu-IVIG and those assigned placebo, assess the feasibility of enrollment, evaluate randomization and blinding procedures, and possibly obtain some preliminary data on efficacy that may be used to inform sample size and study procedures for the clinical outcomes study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

• INCLUSION CRITERIA:

1. Signed informed consent

2. Age greater than or equal to 18 years of age

3. Outpatients or inpatients who are PCR or rapid Ag positive for influenza A or B preferably within 24 hours and no later than 6 days from symptom onset

4. Onset of illness no more than 6 days before randomization, defined as when the patient first experienced at least one respiratory symptom, constitutional symptom or fever

5. For women of child-bearing potential, a negative pregnancy test within one day prior to randomization and a willingness to abstain from sexual intercourse or use at least 1 form of hormonal or barrier contraception through Day 28 of the study

6. Willingness to have blood and respiratory samples obtained and stored

EXCLUSION CRITERIA:

1. If hospitalized, admitted for reasons other than influenza or complications of influenza

2. Women who are pregnant or breast-feeding

3. Strong clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily bacterial in origin.

4. Prior treatment with any investigational drug therapy within 30 days prior to screening

5. History of allergic reaction to blood or plasma products (as judged by the investigator)

6. Known IgA deficiency

7. A pre-existing condition or use of medication that, in the opinion of the investigator, may place the individual at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy)

8. Serum creatinine greater than or equal to 1.5 x ULN or known active kidney disease that may affect drug pharmacokinetics (e.g., nephrotic syndrome)

9. Presence of any pre-existing illness that, in the opinion of the investigator, would place the individual at an unreasonably increased risk through participation in this study

10. Patients who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol

11. Medical conditions for which receipt of 500mL volume may be dangerous to the patient (e.g., decompensated congestive heart failure)

12. Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• Intravenous hyperimmune immunoglobulin (Flu-IVIG)

• Placebo

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Miami Valley Hospital	Dayton	Ohio
United States	Denver Public Health	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California at San Diego	San Diego	California
United States	George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Dwyer DE; INSIGHT Influenza Study Group. Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach: the INSIGHT FLU 002 and FLU 003 studies. Vaccine. 2011 Jul 22;29 Suppl 2:B56-62. doi: 10.1016/j.vaccine.2011.04.105. — View Citation

Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006 Oct 17;145(8):599-609. Epub 2006 Aug 29. — View Citation

Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quiñones-Falconi F, Bautista E, Ramirez-Venegas A, Rojas-Serrano J, Ormsby CE, Corrales A, Higuera A, Mondragon E, Cordova-Villalobos JA; INER Working Group on Influenza. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009 Aug 13;361(7):680-9. doi: 10.1056/NEJMoa0904252. Epub 2009 Jun 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Length of hospital stay (for hospitalized participants)		Measured through the participant's hospital stay	No
Other	Self-reported functional status and symptoms on Days 3 and 7		Measured through Day 7	No
Other	Adverse effects of the study treatment		Measured through Day 28	Yes
Primary	Hemagglutination Inhibition (HAI) titer for each influenza strain (H1N1, H3N2, B) taken 1 hour postinfusion compared to predicted levels.		1 hour	No
Secondary	Compare HAI titers in active drug versus placebo recipients at 1 hour post-infusion, and Study Days 1, 3, and 7 according to the strain and subtype of virus with which participants are infected	assessment of influenza viral replication by Day 3; preliminary assessment of possible antiviral efficacy	Measured through Day 7	No