H7N9 Mix and Match With MF59 in Healthy Adults

NCT01938742 | Completed Phase 2

• 2 other identifiers: 13-0032HHSN272200800005C
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase II randomized, double-blinded, controlled study in up to 700 males and non-pregnant females, 19 to 64 years old, inclusive, designed to assess the safety, reactogenicity, and immunogenicity of a monovalent influenza A/H7N9 virus vaccine administered at different dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with and without MF59 adjuvant and without adjuvant (15 mcg of HA/0.5 mL dose and 45 mcg of HA/0.75 mL dose). Subjects will receive two doses via intramuscular injection, approximately 21 days apart. Safety, reactogenicity, and immunogenicity data will be collected at standard time points with safety follow-up to continue through one year post dose 2. The duration of the study for each subject will be approximately 13 months.

Conditions

Influenza

Keywords

A/H7N9,Adjuvant,Immunogenicity,Influenza,MF59,Monovalent,Vaccine

Outcome Measures

Primary Outcomes (4)

• Occurrence of solicited injection site and systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination.

  Day 0 through Day 29

• Occurrence of study vaccine-related serious adverse events from the time of the first study vaccination through approximately 13 months after the first study vaccination.

  Day 0 through Day 386

• Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at approximately 21 days after the second study vaccination.

  Day 42 (21 days post second study vaccination)

• Percentage of subjects achieving seroconversion (pre-vaccination HAI titer <1:10 and post-vaccination HAI titer >/=1:40 or pre-vaccination HAI titer >/=1:10,minimum four-fold rise in post-vaccination HAI antibody titer).

  Day 42 (21 days post second study vaccination)

Secondary Outcomes (9)

• Geometric Mean Titers of serum HAI and Neut antibody at baseline and at approximately 8 and 21 days after each study vaccination.

  Day 0, 8, 21, 29, and 42

• Occurrence of new-onset chronic medical conditions through 13 months after the first study vaccination

  Through Day 386 (13 months after the first vaccination)

• Occurrence of unsolicited adverse events from the time of the first study vaccination through approximately 21 days after the last study vaccination.

  Day 42 (21 days post last study vaccination)

• Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at approximately 8 days after the second study vaccination.

  Day 29 (8 days after the second study vaccination)

• Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at baseline and at approximately 8 and 21 days after the first study vaccination

  Day 0, 8 and 21

Study Arms (7)

Group 1

EXPERIMENTAL

100 subjects receive 3.75mcg sanofi A/H7N9 antigen plus Novartis MF59 adjuvant on Day 0 and 21

Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59

Group 2

EXPERIMENTAL

100 subjects receive 7.5mcg sanofi A/H7N9 antigen plus Novartis MF59 adjuvant on Day 0 and 21

Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59

Group 3

EXPERIMENTAL

100 subjects receive 15mcg sanofi A/H7N9 antigen plus Novartis MF59 adjuvant on Day 0 and 21

Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59

Group 4

EXPERIMENTAL

100 subjects receive 15mcg sanofi A/H7N9 antigen plus Novartis MF59 adjuvant on Day 0 and 15mcg sanofi A/H7N9 antigen on Day 21

Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59

Group 5

EXPERIMENTAL

100 subjects receive 15mcg sanofi A/H7N9 antigen on Day 0 and 15mcg sanofi A/H7N9 antigen plus Novartis MF59 adjuvant on Day 21

Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59

Group 6

EXPERIMENTAL

100 subjects receive 15mcg sanofi A/H7N9 antigen on Day 0 and 21

Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013

Group 7

EXPERIMENTAL

100 subjects receive 45mcg sanofi A/H7N9 antigen on Day 0 and 21

Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013

Interventions

Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013 BIOLOGICAL

Monovalent influenza A/H7N9 virus vaccine for intramuscular use is a sterile, clear and slightly opalescent suspension. sanofi A/H7N9 antigen. Group 1 receives 3.75mcg A/H7N9 IM on days 1 and 21, Group 2 receives 7.5 mcg IM on days 1 and 21, Group 3, 4, 5, \& 6 receives 15 mcg IM on days 1 and 21, and Group 7 receives 45 mcg IM on days 1 and 21.

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6; Group 7

MF59 DRUG

MF59 adjuvant is an oil-in-water emulsion composed of a small amount of squalene administered with different dosages. Group 1, 2 \& 3 receives 0.7 ml of MF59 Intramuscularly (IM) on days 0 and 21. Group 4 receives MF59 on day 0, Group 5 receives MF59 on Day 21.

Group 1; Group 2; Group 3; Group 4; Group 5

Eligibility Criteria

• Age: 19 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Have an acute illness within 72 hours prior to study vaccination. -Have any condition that, in the opinion of the site principal investigator or appropriate sub-investigator, would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or confound the interpretation of the results. -Have an acute or chronic medical condition that, in the opinion of the site principal investigator or appropriate sub-investigator, would render vaccination unsafe, or would interfere with the evaluation of responses. -Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination. -Have known active neoplastic disease or a history of any hematologic malignancy. -Have known HIV, hepatitis B, or hepatitis C infection. -Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine. -Have a history of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines. -Have a history of Guillain-Barré Syndrome. - Have a history of neuralgia, paresthesia, neuritis, convulsions, or encephalomyelitis within 90 days prior to study vaccination. -Have a history of autoimmune disease, including but not limited to neuroinflammatory diseases, vasculitis, clotting disorders, dermatitis, arthritis, thyroiditis, or muscle, liver or kidney disease. -Have a history of alcohol or drug abuse within 5 years prior to study vaccination. -Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations. -Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination. -Have taken oral or parenteral corticosteroids of any dose within 30 days prior to study vaccination. -Have taken high-dose inhaled corticosteroids within 30 days prior to study vaccination. High-dose defined as \>800mcg/day of beclomethasone dipropionate CFC or equivalent. -Received any licensed live vaccine within 30 days or any licensed inactivated vaccine within 14 days prior to the first study vaccination or planned receipt of any vaccine from the first study vaccination through the follow-up visit at approximately 21 days after the last study vaccination. This is inclusive of licensed seasonal influenza vaccines. -Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90 days prior to study vaccination. -Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 30 days prior to the first study vaccination, or expects to receive an experimental agent other than from participation in this study during the 13-month study period. -Are participating or plan to participate in another clinical trial with an interventional agent (licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication) during the 13-month study period. -Prior participation in a clinical trial of influenza A/H7 vaccine and assigned to a group receiving influenza A/H7 vaccine (does not apply to documented placebo recipients) or have a history of A/H7 actual or potential exposure or infection prior to the first study vaccination. -Plan to travel outside the U.S. (continental U.S., Hawaii and Alaska) in the time between the first study vaccination and 42 days after the first study vaccination. -Female subjects who are breastfe eding or plan to breastfeed at any given time from the first study vaccination until 30 days after their last study vaccination. -Blood donation within 30 days prior to enrollment and within 30 days after the last blood draw (only for a subset of healthy adult subjects - up to 75 volunteers, 19-64 years old, enrolled at the Emory VTEU site, who consent to blood donation for the immunology exploratory assays).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, 30030-1705, United States

Location

University of Iowa - Infectious Disease Clinic

Iowa City, Iowa, 52242-1009, United States

Location

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3026, United States

Location

University of Texas Medical Branch - Pediatrics - Infectious Diseases and Immunology - Galveston

Galveston, Texas, 77555-5302, United States

Location

Related Publications (2)

• Mulligan MJ, Bernstein DI, Winokur P, Rupp R, Anderson E, Rouphael N, Dickey M, Stapleton JT, Edupuganti S, Spearman P, Ince D, Noah DL, Hill H, Bellamy AR; DMID 13-0032 H7N9 Vaccine Study Group. Serological responses to an avian influenza A/H7N9 vaccine mixed at the point-of-use with MF59 adjuvant: a randomized clinical trial. JAMA. 2014 Oct 8;312(14):1409-19. doi: 10.1001/jama.2014.12854.

  PMID: 25291577 RESULT

• Lai L, Rouphael N, Xu Y, Kabbani S, Beck A, Sherman A, Anderson EJ, Bellamy A, Weiss J, Cross K, Mulligan MJ. An Oil-in-Water adjuvant significantly increased influenza A/H7N9 split virus Vaccine-Induced circulating follicular helper T (cTFH) cells and antibody responses. Vaccine. 2022 Nov 22;40(49):7065-7072. doi: 10.1016/j.vaccine.2022.09.041. Epub 2022 Oct 21.

  PMID: 36273986 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; MF59 oil emulsion

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2013
• First Posted: September 10, 2013
• Study Start: September 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: December 12, 2016

Record last verified: 2015-07

Locations

US (4)