2013/2017 H7N9 Prime-Boost Interval

NCT ID: NCT03589807

Last Updated: 2021-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-21
• Study Completion Date: 2020-06-14

Brief Summary

This is a trial designed to assess the safety, reactogenicity and immunogenicity of one or two doses of monovalent inactivated split influenza 2013 and 2017 A/H7N9 virus vaccines administered intramuscularly at different dosages, given with or without AS03 adjuvant, using different vaccination schedules. This trial will enroll up to 180 males and non-pregnant females, 19 to 50 years of age, who are in good health and who are influenza A/H7 naïve. Subjects will be randomly assigned to 1 of 6 treatment arms (30 subjects per arm) to evaluate the interval between the first and second doses and the presence of the adjuvant in the first and second doses. The neuraminidase-specific antibody response and the neuraminidase content of the Inactivated Influenza Virus Vaccine will be determined using tests that are currently under development. Study duration is approximately 22 months with subject participation duration of approximately 18 months. The primary objectives of the study are: 1) to assess the safety and reactogenicity of 2013 and 2017 A/H7N9 IIVs given with or without AS03 adjuvant following receipt of each study vaccine; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of the second study vaccine.

Detailed Description

This is a Phase II trial designed to assess the safety, reactogenicity and immunogenicity of one or two doses of monovalent inactivated split influenza 2013 and 2017 A/H7N9 virus vaccines (2013 and 2017 A/H7N9 IIVs) administered intramuscularly at different dosages (3.75 or 15 mcg of hemagglutinin (HA) per dose), given with or without AS03 adjuvant, using different heterologous and homologous prime-boost vaccination schedules. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. This trial will enroll up to 180 males and non-pregnant females, 19 to 50 years of age, inclusive, who are in good health and meet all eligibility criteria and who are influenza A/H7 vaccine/infection naïve by medical history. Subjects will be randomly assigned to 1 of 6 treatment arms (30 subjects per arm) evaluating the interval between the priming (first) and boosting (second) doses and the presence of the adjuvant in the priming (first) and boosting (second) doses. The neuraminidase-specific antibody response and the neuraminidase content of the Inactivated Influenza Virus Vaccine will be determined using tests that are currently under development. Study duration is approximately 22 months with subject participation duration of approximately 18 months. The primary objectives of the study are: 1) to assess the safety and reactogenicity of 2013 and 2017 A/H7N9 IIVs given with or without AS03 adjuvant following receipt of each study vaccine; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of the second study vaccine. The secondary objectives are: 1) to assess unsolicited non-serious adverse events (AEs) following receipt of each study vaccine; 2) to assess medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs), following receipt of each study vaccine; 3) to assess the kinetics and durability of serum HAI and Neut antibody responses following receipt of each study vaccine.

Conditions

Avian Influenza; Influenza Immunisation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Heterologous Arm 1

3.75 mcg per 0.5 ml dose of 2013 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 and 3.75 mcg per 0.5 ml dose of 2017 A/H7N9 IIV + ASO3 adjuvant administered intramuscularly on Day 22. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. N=30

Group Type: EXPERIMENTAL

A/H7N9

Intervention Type: BIOLOGICAL

Monovalent split 2017 A/H7N9 Inictivated Influenza Virus vaccine containing the HA and 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).

AS03

Intervention Type: DRUG

AS03 oil-in-water emulsion adjuvant.

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

Intervention Type: BIOLOGICAL

Monovalent split 2013 A/H7N9 Inavtivated Influenza Virus vaccine containing the HA and NA from avian influenza A/Shanghai/2/2013 (H7N9) and the PB2, PB1, PA, NP, M and NS from A/Puerto Rico/8/1934 (H1N1).

Phosphate Buffered Saline (PBS) diluent

Intervention Type: OTHER

Diluent for Influenza Virus Vaccine.

Heterologous Arm 2

3.75 mcg per 0.5 ml dose of 2013 A/H7N9 IIV + AS03 adjuvant administered intramuscularly on Day 1 and 3.75 mcg per 0.5 ml dose of 2017 A/H7N9 IIV + ASO3 adjuvant administered intramuscularly on Day 121. PBS diluent may be used to achieve targeted dosages. N=30

Group Type: EXPERIMENTAL

A/H7N9

Intervention Type: BIOLOGICAL

Monovalent split 2017 A/H7N9 Inictivated Influenza Virus vaccine containing the HA and 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).

AS03

Intervention Type: DRUG

AS03 oil-in-water emulsion adjuvant.

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

Intervention Type: BIOLOGICAL

Monovalent split 2013 A/H7N9 Inavtivated Influenza Virus vaccine containing the HA and NA from avian influenza A/Shanghai/2/2013 (H7N9) and the PB2, PB1, PA, NP, M and NS from A/Puerto Rico/8/1934 (H1N1).

Phosphate Buffered Saline (PBS) diluent

Intervention Type: OTHER

Diluent for Influenza Virus Vaccine.

Heterologous Arm 3

3.75 mcg per 0.5 ml dose of 2013 A/H7N9 IIV + AS03 adjuvant administered intramuscularly on Day 1 and 15 mcg per 0.5 ml dose of 2017 A/H7N9 IIV administered intramuscularly on Day 121. PBS diluent may be used to achieve targeted dosages. N=30

Group Type: EXPERIMENTAL

A/H7N9

Intervention Type: BIOLOGICAL

Monovalent split 2017 A/H7N9 Inictivated Influenza Virus vaccine containing the HA and 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).

AS03

Intervention Type: DRUG

AS03 oil-in-water emulsion adjuvant.

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

Intervention Type: BIOLOGICAL

Monovalent split 2013 A/H7N9 Inavtivated Influenza Virus vaccine containing the HA and NA from avian influenza A/Shanghai/2/2013 (H7N9) and the PB2, PB1, PA, NP, M and NS from A/Puerto Rico/8/1934 (H1N1).

Phosphate Buffered Saline (PBS) diluent

Intervention Type: OTHER

Diluent for Influenza Virus Vaccine.

Homologous Arm 1

3.75 mcg per 0.5 ml dose of 2017 A/H7N9 IIV + AS03 adjuvant administered intramuscularly on Day 1 and Day 22. PBS diluent may be used to achieve targeted dosages. N=30

Group Type: EXPERIMENTAL

A/H7N9

Intervention Type: BIOLOGICAL

Monovalent split 2017 A/H7N9 Inictivated Influenza Virus vaccine containing the HA and 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).

AS03

Intervention Type: DRUG

AS03 oil-in-water emulsion adjuvant.

Phosphate Buffered Saline (PBS) diluent

Intervention Type: OTHER

Diluent for Influenza Virus Vaccine.

Homologous Arm 2

3.75 mcg per 0.5 ml dose of 2017 A/H7N9 IIV + AS03 adjuvant administered intramuscularly on Day 1 and Day 121. PBS diluent may be used to achieve targeted dosages. N=30

Group Type: EXPERIMENTAL

A/H7N9

Intervention Type: BIOLOGICAL

Monovalent split 2017 A/H7N9 Inictivated Influenza Virus vaccine containing the HA and 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).

AS03

Intervention Type: DRUG

AS03 oil-in-water emulsion adjuvant.

Phosphate Buffered Saline (PBS) diluent

Intervention Type: OTHER

Diluent for Influenza Virus Vaccine.

Homologous Arm 3

3.75 mcg per 0.5 ml dose of 2017 A/H7N9 IIV + AS03 Adjuvant administered intramuscularly on Day 1 and 15 mcg per 0.5 ml dose of 2017 A/H7N9 IIV administered intramuscularly on Day 121. PBS diluent may be used to achieve targeted dosages. N=30

Group Type: EXPERIMENTAL

A/H7N9

Intervention Type: BIOLOGICAL

Monovalent split 2017 A/H7N9 Inictivated Influenza Virus vaccine containing the HA and 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).

AS03

Intervention Type: DRUG

AS03 oil-in-water emulsion adjuvant.

Phosphate Buffered Saline (PBS) diluent

Intervention Type: OTHER

Diluent for Influenza Virus Vaccine.

Interventions

A/H7N9

Monovalent split 2017 A/H7N9 Inictivated Influenza Virus vaccine containing the HA and 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).

Intervention Type: BIOLOGICAL

AS03

AS03 oil-in-water emulsion adjuvant.

Intervention Type: DRUG

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

Monovalent split 2013 A/H7N9 Inavtivated Influenza Virus vaccine containing the HA and NA from avian influenza A/Shanghai/2/2013 (H7N9) and the PB2, PB1, PA, NP, M and NS from A/Puerto Rico/8/1934 (H1N1).

Intervention Type: BIOLOGICAL

Phosphate Buffered Saline (PBS) diluent

Diluent for Influenza Virus Vaccine.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Provide written informed consent prior to initiation of any study procedures.

2. Are able to understand and comply with planned study procedures and be available for all study visits.

3. Must agree to the collection of venous blood per protocol.

4. 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.

5. Are males or non-pregnant females, 19 to 50 years of age, inclusive.

6. Are in good health.

Exclusion Criteria

7. Oral temperature is less than 100.0 degrees Fahrenheit.

8. Pulse is 47 to 100 beats per minute, inclusive.

9. Systolic blood pressure is 85 to 150 mmHg, inclusive.

10. Diastolic blood pressure is 55 to 95 mmHg, inclusive.

11. Erythrocyte Sedimentation Rate (ESR) is less than 30 mm per hour.

12. 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.

-- 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").

13. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.

1. 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.

2. 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.

3. Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.

4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.

5. Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma, treated, skin cancers are permitted.

6. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.

7. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine.

8. Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.

9. Have a personal or family history of narcolepsy.

10. Have a history of Guillian-Barre Syndrome (GBS).

11. Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.

12. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).

13. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

14. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.

• As determined by the site Principal Investigator or appropriate sub-investigator.

15. 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.

16. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination.

17. Have taken high-dose inhaled corticosteroids within 30 days prior to each study vaccination.

• High-dose defined as per age as using inhaled high-dose per reference chart in the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published in UPTODATE.

18. Received a licensed live vaccine within 30 days prior to the first study vaccination, or plan to receive a licensed live vaccine within 30 days before or after each study vaccination.

19. Received or plan to receive a licensed, inactivated vaccine (excluding all licensed, seasonal IIVs) within 14 days before or after each study vaccination.

20. Received or plan to receive a licensed, seasonal IIV within 21 days before or after each study vaccination

21. Received immunoglobulin or other blood products (except Rho D immunoglobulin) within 90 days prior to each study vaccination.

22. Received an experimental agent within 30 days prior to the first study vaccination, or expect to receive an experimental agent during the trial-reporting period.

• Including vaccine, drug, biologic, device, blood product, or medication.

-- Other than from participation in this trial.

--- Approximately 12 months after the last study vaccination.

23. Are participating or plan to participate in another clinical trial with an interventional agent that will be received during the trial-reporting period.

• Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication.

-- Approximately 12 months after the last study vaccination.

24. Received or plan to receive an influenza A/H7 vaccine or have a history of influenza A/H7 subtype infection.

• And assigned to a treatment arm receiving influenza A/H7 vaccine, i.e., does not apply to documented placebo recipients.

25. Had substantial direct contact with live or freshly slaughtered poultry or pigeons while in mainland China within the past five years.

• Substantial contact is defined as visited a poultry farm and/or a live poultry market.

26. Occupational exposure to or substantial direct physical contact with birds in the past year and through the 21 days after the last study vaccination.

• Exposure to free range chickens in the yard is exclusionary. Casual contact with birds at petting zoos or county or state fairs, or having pet birds does not exclude subjects from study participation.

27. Female subjects who are breastfeeding or plan to breastfeed at any given time from the first study vaccination until 30 days after the last study vaccination.

28. Plan to travel outside the US (continental US, Hawaii, and Alaska) from the time of each study vaccination through 21 days after each study vaccination.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Emory Children's Center - Pediatric Infectious Diseases

Atlanta, Georgia, United States

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, United States

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, United States

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, United States

Duke Human Vaccine Institute - Duke Vaccine and Trials Unit

Durham, North Carolina, United States

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 39756216 (View on PubMed)

Rostad CA, Atmar RL, Walter EB, Frey S, Meier JL, Sherman AC, Lai L, Tsong R, Kao CM, Raabe V, El Sahly HM, Keitel WA, Whitaker JA, Smith MJ, Schmader KE, Swamy GK, Abate G, Winokur P, Buchanan W, Cross K, Wegel A, Xu Y, Yildirim I, Kamidani S, Rouphael N, Roberts PC, Mulligan MJ, Anderson EJ. A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered With and Without AS03 Adjuvant in Healthy US Adults. Clin Infect Dis. 2024 Jun 14;78(6):1757-1768. doi: 10.1093/cid/ciae173.

Reference Type: DERIVED

PMID: 38537255 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

HHSN272201300018I

Identifier Type: -

Identifier Source: secondary_id

17-0078

Identifier Type: -

Identifier Source: org_study_id