2017 A/H7N9 IIV Revaccination

NCT03738241 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17-0090HHSN272201300015I
• Study Type: interventional
• Target: 304
• Locations: 1 country
• Sites: 9

Brief Summary

This is a Phase II clinical trial in up to 420 males and non-pregnant females, 19 to 70 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of one dose of a monovalent inactivated split influenza 2017 A/H7N9 virus vaccine (2017 A/H7N9 IIV), administered intramuscularly (IM) at 3.75 mcg hemagglutinin (HA) per dose, given with or without AS03 adjuvant to subjects primed with a monovalent inactivated split influenza 2013 A/H7N9 virus vaccine (2013 A/H7N9 IIV) in DMID Protocols 13-0032 and 13-0033, or to those who are A/H7 IIV-naïve. Phosphate buffered saline (PBS) diluent will be used to achieve the targeted dosage. The study will be conducted at 9 Vaccine and Treatment Evaluation Unit (VTEU) sites (including their subcontractors). Study duration is approximately 17 months with subject participation duration up to 13 months. The primary objectives are: 1) to assess the safety and reactogenicity of 2017 A/H7N9 IIV given with or without AS03 adjuvant following receipt of one dose of study vaccine; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of the study vaccine.

Conditions

Avian Influenza; Influenza Immunisation

Keywords

A/H7N9 Inactivated Influenza Vaccine; AS03 Adjuvant; Immunogenicity; Influenza; Phase II; Reactogenicity; Safety; Vaccine

Outcome Measures

Primary Outcomes (10)

• Geometric Mean Titers (GMT) of Serum Hemagglutination Inhibition (HAI) Antibodies on Day 22 Against the 2017 Influenza A/H7N9 Vaccine Virus

  Blood was collected for HAI assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm and stratum from the available results at 21 days post study vaccination (Day 22).

  Day 22

• Geometric Mean Titers (GMT) of Serum Neutralizing (Neut) Antibodies on Day 22 Against the 2017 Influenza A/H7N9 Vaccine Virus

  Blood was collected for Neutralizing assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm and stratum from the available results at 21 days post study vaccination (Day 22).

  Day 22

• Number of Participants Reporting Serious Adverse Events (SAEs)

  SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect.

  Day 1 through Day 366

• Number of Participants Reporting Clinical Safety Laboratory Adverse Events (AEs)

  Laboratory parameters include alanine aminotransferase (ALT), bilirubin, creatinine, hemoglobin, platelets and white blood cells (WBC). Thresholds for adverse events were considered as ALT 44 IU/L or greater (female) or 61 IU/L or greater (male); bilirubin 1.30 mg/dL or greater; creatinine 1.1 mg/dL or greater (female) or 1.4 mg/dL or greater (male); hemoglobin 11.4 g/dL or lower (female) or 12.4 g/dL or lower (male); platelets 139 x10\^3/µL or below or 416 x10\^3/µL or greater; or WBC or 3.9 x10\^3/µL or lower or 10.6 x10\^3/µL or higher.

  Day 1 to Day 8

• Number of Participants Reporting Solicited Injection Site Reactogenicity Events

  Injection site AEs solicited on a memory aid provided to participants included Pain, Tenderness, Itching/Pruritus, Ecchymosis/Bruising (functional grade based on interference with daily activities), Ecchymosis/Bruising (any measured value \>0mm), Erythema/Redness (functional grade), Erythema/ Redness (any measured value \>0mm), Induration/Swelling (functional grade), and Induration/Swelling (any measured value \>0mm). Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days at or following the first vaccination.

  Day 1 through Day 8

• Number of Participants Reporting Solicited Systemic Reactogenicity Events

  Systemic AEs solicited on a memory aid provided to participants included Elevated Oral Temperature, Feverishness, Fatigue, Malaise, Myalgia, Arthralgia, Headache, and Nausea. Participants are considered reporting the systemic AE if they reported mild or greater severity at any time during the 8 days at or following the first vaccination.

  Day 1 through Day 8

• Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibody Titer of 1:40 or Greater on Day 22 Against the 2017 Influenza A/H7N9 Vaccine Virus

  Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with HAI titer \>= 1:40 was calculated for each study arm and stratum from the available results at 21 days post study vaccination (Day 22).

  Day 22

• Percentage of Participants Achieving Neutralizing (Neut) Antibody Titer of 1:40 or Greater on Day 22 Against the 2017 Influenza A/H7N9 Vaccine Virus

  Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with Neut titer \>= 1:40 was calculated for each study arm and stratum from the available results at 21 days post study vaccination (Day 22).

  Day 22

• Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibody Seroconversion on Day 22 Against the 2017 Influenza A/H7N9 Study Vaccine Virus

  Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as HAI pre-vaccination titer \<1:10 and post-vaccination titer \>= 1:40 or pre-vaccination titer \>= 1:10 and minimum 4-fold rise in post-vaccination antibody titer. 21 days after study vaccination is Day 22.

  Day 22

• Percentage of Participants Achieving Neutralizing (Neut) Antibody Seroconversion on Day 22 Against the 2017 Influenza A/H7N9 Study Vaccine Virus

  Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as Neut pre-vaccination titer \<1:10 and post-vaccination titer \>= 1:40 or pre-vaccination titer \>= 1:10 and minimum 4-fold rise in post-vaccination antibody titer. 21 days after study vaccination is Day 22.

  Day 22

Secondary Outcomes (20)

• Geometric Mean Titers (GMT) of Serum Hemagglutination Inhibition (HAI) Antibodies on Day 8 Against the 2017 Influenza A/ H7N9 Vaccine Virus

  Day 8

• Geometric Mean Titers (GMT) of Serum Hemagglutination Inhibition (HAI) Antibodies on Day 181 Against the 2017 Influenza A/ H7N9 Vaccine Virus

  Day 181

• Geometric Mean Titers (GMT) of Serum Neutralizing (Neut) Antibodies on Day 8 Against the 2017 Influenza A/H7N9 Vaccine Virus

  Day 8

• Geometric Mean Titers (GMT) of Serum Neutralizing (Neut) Antibodies on Day 181 Against the 2017 Influenza A/H7N9 Vaccine Virus

  Day 181

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies on Day 22 Against the 2013 Influenza A/H7N9 Vaccine Virus (Priming Vaccine Virus)

  Day 22

Study Arms (5)

Arm 1

EXPERIMENTAL

Participants will have prior administration of 2013 A/H7N9 IIV with MF59. Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=50) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=50). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages.

Biological: A/H7N9; Drug: AS03; Other: Phosphate Buffered Saline (PBS) diluent

Arm 2

EXPERIMENTAL

Participants will have prior administration of 2013 A/H7N9 IIV with AS03. Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=50) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=50). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages.

Biological: A/H7N9; Drug: AS03; Other: Phosphate Buffered Saline (PBS) diluent

Arm 3

EXPERIMENTAL

Participants will have prior administration of 2013 A/H7N9 IIV 15 mcg or 45 mcg unadjuvanted. Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=50) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=50). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages.

Biological: A/H7N9; Drug: AS03; Other: Phosphate Buffered Saline (PBS) diluent

Arm 4

EXPERIMENTAL

Participants will have prior administration of 2013 A/H7N9 IIV + MF59 or AS03 (1st) then 2013 A/H7N9 IIV 15 mcg (2nd). Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=30) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=30). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages.

Biological: A/H7N9; Drug: AS03; Other: Phosphate Buffered Saline (PBS) diluent

Arm 5

EXPERIMENTAL

Participants who are A/H7 IIV-Naïve. Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=30) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=30). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages.

Biological: A/H7N9; Drug: AS03; Other: Phosphate Buffered Saline (PBS) diluent

Interventions

A/H7N9 BIOLOGICAL

Monovalent split 2017 A/H7N9 Inactivated Influenza Virus Vaccine containing the Hemagglutinin (HA) and Neuraminidase (NA) from low pathogenic avian influenza A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, NP, M and NS from A/Puerto Rico/8/1934 (H1N1). The HA content of the 2017 A/H7N9 vaccine formulations were determined by Single Radial Immunodiffusion (SRID) assay to be approximately two times higher (14.45 mcg of HA per 0.5 mL dose) than the targeted HA content on the label (7.5 mcg of HA per 0.5 mL dose).

Arm 1; Arm 2; Arm 3; Arm 4; Arm 5

AS03 DRUG

AS03 oil-in-water emulsion-based adjuvant system containing DL-alpha-tocopherol, squalene, polysorbate 80, and a buffer.

Arm 1; Arm 2; Arm 3; Arm 4; Arm 5

Phosphate Buffered Saline (PBS) diluent OTHER

0.006M PBS diluent for Influenza Virus Vaccine.

Arm 1; Arm 2; Arm 3; Arm 4; Arm 5

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent prior to initiation of any study procedures.
• Are able to understand and comply with planned study procedures and be available for all study visits.
• Must agree to the collection of venous blood per protocol.
• Must agree to have residual specimens and samples/specimens collected during this trial specifically for the purpose of future research stored for future research use.
• Are males or non-pregnant females, 19 to 70 years of age, inclusive.

You may not qualify if:

• Oral temperature is less than 100.0 degrees Fahrenheit.
• Pulse is 47 to 100 beats per minute, inclusive.
• Systolic blood pressure is 85 to 150 mmHg, inclusive.
• Diastolic blood pressure is 55 to 95 mmHg, inclusive.
• Erythrocyte Sedimentation Rate (ESR) is less than 30 mm per hour.
• Women of childbearing potential\*\* must use an acceptable contraception method\*\*\* from 30 days before study vaccination until 60 days after study vaccination.
• \*\*Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \<1 year has passed since the last menses if menopausal.
• \*\*\*Includes non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the study vaccination, barrier methods such as condoms or diaphragms/cervical cap with spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").
• Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.
• Received 1 or 2 doses of 2013 A/H7N9 IIV with or without AS03 or MF59 adjuvant in DMID Protocols 13-0032 or 13-0033, or are A/H7 IIV-naïve.
• Have an acute illness\*, as determined by the site PI or appropriate sub-investigator, within 72 hours prior to study vaccination.
• \*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
• Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation\*\*.
• \*\*Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial.
• Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.

Sponsors & Collaborators

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

Study Sites (9)

Emory Children's Center - Pediatric Infectious Diseases

Atlanta, Georgia, 30322-1014, United States

Location

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

University of Maryland Baltimore - School of Medicine - Medicine

Baltimore, Maryland, 21201-1509, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3039, United States

Location

Vanderbilt University Medical Center - Infectious Diseases

Nashville, Tennessee, 37232-0011, United States

Location

The University of Texas Medical Branch - Sealy Center for Vaccine Development (SCVD)

Galveston, Texas, 77555-1121, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

Kaiser Permanente Washington Health Research Institute - Vaccines and Infectious Diseases

Seattle, Washington, 98101-1466, United States

Location

Related Publications (2)

• El Sahly HM, Anderson EJ, Jackson LA, Neuzil KM, Atmar RL, Bernstein DI, Chen WH, Creech CB, Frey SE, Goepfert P, Meier J, Phadke V, Rouphael N, Rupp R, Stapleton JT, Spearman P, Walter EB, Winokur PL, Yildirim I, Williams TL, Oshinsky J, Coughlan L, Nijhuis H, Pasetti MF, Krammer F, Stadlbauer D, Nachbagauer R, Tsong R, Wegel A, Roberts PC. Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens. Vaccine. 2025 Feb 15;47:126689. doi: 10.1016/j.vaccine.2024.126689. Epub 2025 Jan 4.

  PMID: 39756216 DERIVED

• El Sahly HM, Yildirim I, Frey SE, Winokur P, Jackson LA, Bernstein DI, Creech CB, Chen WH, Rupp RE, Whitaker JA, Phadke V, Hoft DF, Ince D, Brady RC, Edwards KM, Ortiz JR, Berman MA, Weiss J, Wegel A; DMID 17-0090 Study Group. Safety and Immunogenicity of a Delayed Heterologous Avian Influenza A(H7N9) Vaccine Boost Following Different Priming Regimens: A Randomized Clinical Trial. J Infect Dis. 2024 Feb 14;229(2):327-340. doi: 10.1093/infdis/jiad276.

  PMID: 37466221 DERIVED

MeSH Terms

Conditions

Influenza in Birds; Influenza, Human

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Hana El Sahly, MD, FIDSA
• Organization: Baylor College of Medicine

hana.elsahly@bcm.edu

713-798-2058

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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: November 8, 2018
• First Posted: November 13, 2018
• Study Start: December 18, 2018
• Primary Completion: June 19, 2020
• Study Completion: June 19, 2020
• Last Updated: July 30, 2021
• Results First Posted: July 1, 2021

Record last verified: 2018-11-08

Locations

US (9)