Sanofi 2017 H7N9 With/Without AS03 in Adults/Elderly

NCT03312231 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 17-0075
• Study Type: interventional
• Target: 720
• Locations: 1 country
• Sites: 5

Brief Summary

This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females 19 years and older that is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza A/H7N9 virus vaccine (2017 H7N9 IIV) administered at different dosages given with AS03 adjuvant and phosphate buffered saline (PBS) diluent, with AS03 adjuvant only, and without adjuvant. Eligible subjects will be randomized into 5 study groups, stratified by age. The study will enroll up to 420 individuals 19-64 years old and up to 300 individuals who are 65 years old and older. Study duration is approximately 16 months with subject participation duration approximately 13 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart given with or without AS03 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age of recipient.

Conditions

Avian Influenza; Influenza Immunisation

Keywords

A/H7N9; Immunogenicity; Influenza; Safety; Sanofi Pasteur; Vaccine

Outcome Measures

Primary Outcomes (13)

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies

  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 from the available results at 21 days after the second dose of H7N9.

  Day 43

• Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Antibodies

  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 from the available results at 21 days after the second dose of H7N9.

  Day 43

• Number of Participants With Clinical Safety Laboratory Adverse Events

  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 8

• Number of Participants With Clinical Safety Laboratory Adverse Events

  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 29

• Number of Participants Reporting Solicited Injection Site 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 dailyactivities), 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 to Day 8

• Number of Participants Reporting Solicited Injection Site 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 dailyactivities), 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 second vaccination.

  Day 22 to Day 29

• Number of Participants Reporting Study Vaccine-related 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. Events are included if deemed by the investigator to be related to the study product.

  Day 1 to Day 387

• Number of Participants Reporting 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 to Day 8

• Number of Participants Reporting 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 second vaccination.

  Day 22 to Day 29

• Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibodies Titer of 1:40 or Greater

  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 group from the available results at 21 days after second dose of H7N9.

  Day 43

• Percentage of Participants Achieving Neutralizing (Neut) Antibodies Titer of 1:40 or Greater

  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 group from the available results at 21 days after second dose of H7N9.

  Day 43

• Percentage of Participants Achieving Seroconversion Defined by Hemagglutination Inhibition (HAI) Antibodies

  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 or greater and minimum 4-fold rise in post-vaccination antibody titer. 21 days after second dose of H7N9 is Day 43.

  Day 43

• Percentage of Participants Achieving Seroconversion Defined by Neutralizing (Neut) Antibodies

  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 or greater and minimum 4-fold rise in post-vaccination antibody titer. 21 days after second dose of H7N9 is Day 43.

  Day 43

Secondary Outcomes (26)

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies

  Day 1

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies

  Day 8

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies

  Day 22

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies

  Day 29

• Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Antibodies

  Day 1

Study Arms (5)

Group 1

EXPERIMENTAL

3.75 mcg of H7N9 vaccine with PBS diluent plus AS03 adjuvant on days 1 and 22, n=100 (19-64 years old) and n=60 (65 and older)

Drug: AS03; Biological: Inactivated influenza H7N9 vaccine; Other: Phosphate Buffered Saline (PBS) diluent

Group 2

EXPERIMENTAL

7.5 mcg of H7N9 vaccine plus AS03 adjuvant on days 1 and 22, n=100 (19-64 years old) and n=60 (65 and older)

Drug: AS03; Biological: Inactivated influenza H7N9 vaccine

Group 3

EXPERIMENTAL

15 mcg of H7N9 vaccine plus AS03 adjuvant on days 1 and 22, n=100 (19-64 years old) and n=60 (65 and older)

Drug: AS03; Biological: Inactivated influenza H7N9 vaccine

Group 4

EXPERIMENTAL

15 mcg of unadjuvanted H7N9 vaccine on days 1 and 22, n=50 (19-64 years old) and n=30 (65 and older)

Biological: Inactivated influenza H7N9 vaccine

Group 5

EXPERIMENTAL

45 mcg of unadjuvanted H7N9 vaccine on days 1 and 22, n=50 (19-64 years old) and n=30 (65 and older)

Biological: Inactivated influenza H7N9 vaccine

Interventions

AS03 DRUG

Oil-in-water emulsion based adjuvant system.

Group 1; Group 2; Group 3

Inactivated influenza H7N9 vaccine BIOLOGICAL

Monovalent 2017 H7N9 inactivated influenza vaccine

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

Phosphate Buffered Saline (PBS) diluent OTHER

Diluent for 2017 Monovalent Inactivated Influenza A/H7N9 virus vaccine (2017 H7N9 IIV)

Group 1

Eligibility Criteria

• Age: 19 Years - 99 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.
• Are males or non-pregnant females, 19 years of age and older, inclusive.

You may not qualify if:

• Oral temperature is less than 100.0 degrees Fahrenheit.
• Pulse is 47 to 100 bpm, inclusive.
• Systolic blood pressure is 85 to 150 mmHg, inclusive (subjects \<65 years of age), 85 to 160 mmHg, inclusive (subjects = / \> 65 years of age).
• 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 first study vaccination until 60 days after last 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 of the last menses if menopausal.
• \*\*Acceptable contraception 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 first study vaccination, barrier methods such as condoms or diaphragms with spermicide or foam, 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.
• Have an acute illness\*, as determined by the site principal investigator 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 principal investigator 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 principal investigator 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.
• Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.

Sponsors & Collaborators

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

Study Sites (5)

The Hope Clinic of Emory University

Decatur, Georgia, 30030-1705, United States

Location

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

University of Maryland, School of Medicine, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201-1509, United States

Location

Duke Vaccine and Trials Unit

Durham, North Carolina, 27704, United States

Location

Kaiser Permanente Washington Health Research Institute

Seattle, Washington, 98101-1466, United States

Location

Related Publications (1)

• 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

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: Lisa A. Jackson, MD, MPH
• Organization: Kaiser Permanente Washington Health Research Institute

lisa.a.jackson@kp.org

206-442-5216

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: October 12, 2017
• First Posted: October 17, 2017
• Study Start: February 14, 2018
• Primary Completion: September 26, 2019
• Study Completion: September 26, 2019
• Last Updated: September 19, 2024
• Results First Posted: October 12, 2020

Record last verified: 2018-02-06

Locations

US (5)