Systems Biology of Influenza A (H5N1) Virus Monovalent Vaccine With and Without Adjuvant System 03 (AS03)

NCT ID: NCT01910519

Last Updated: 2019-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2015-11-30

Brief Summary

This study will compare the different immune responses to Influenza A (H5N1) Virus Monovalent Vaccine with and without the AS03 adjuvant. The Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant vaccine is approved for use for adults to protect against flu caused by the A/H5N1 "bird flu" virus in Europe but none of the vaccines to be used in the study are approved for use in the United States. The results of this study will help researchers learn about better ways to vaccinate people against the H5N1 flu.

Detailed Description

The influenza virus (a germ) causes influenza or "flu." The flu is an infection of the breathing tubes and the lungs. In recent years, flu viruses that at first only infected birds have begun to infect humans. One of these strains is called avian influenza (A/H5N1 subtype) or "bird flu". Although no human cases of bird flu have been diagnosed in the United States, this strain has caused severe illness and death in several hundred people since late 2003. .

Vaccination is the most effective way of controlling flu and preventing its illness and complications. Vaccines help prevent illness by causing the body to make antibodies that fight infection. One way to improve the effectiveness of a vaccine is to include a substance that can stimulate the immune system to make more antibodies. This type of substance is called an adjuvant; one type of adjuvant is called AS03 (Adjuvant System 03).

Conditions

Influenza A Virus, H5N1 Subtype

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

H5N1 vaccine plus AS03 adjuvant

H5N1 vaccine plus AS03 adjuvant: Influenza A Vaccine with AS03 adjuvant

Participants receive 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant given 21 days apart (i.e., Administer day 1, booster at Day 21).

Group Type: EXPERIMENTAL

H5N1 vaccine plus AS03 adjuvant

Intervention Type: BIOLOGICAL

Administered vaccine: [GlaxoSmithKline] Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted.

Participants receive 2 intramuscular doses of Influenza A (H5N1) Virus with AS03 adjuvant, administered 21 (+/- 3) days apart.

H5N1 vaccine without adjuvant

H5N1 vaccine without adjuvant: Influenza A Vaccine without AS03 adjuvant

Participants receive 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant given 21 days apart (i.e., Administer day 1, booster at Day 21).

Group Type: EXPERIMENTAL

H5N1 vaccine without adjuvant

Intervention Type: BIOLOGICAL

Administered vaccine: [GlaxoSmithKline] Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant.

Participants receive 2 intramuscular doses of Influenza A (H5N1) Virus without adjuvant, administered 21 (+/- 3) days apart.

Interventions

H5N1 vaccine plus AS03 adjuvant

Administered vaccine: [GlaxoSmithKline] Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted.

Participants receive 2 intramuscular doses of Influenza A (H5N1) Virus with AS03 adjuvant, administered 21 (+/- 3) days apart.

Intervention Type: BIOLOGICAL

H5N1 vaccine without adjuvant

Administered vaccine: [GlaxoSmithKline] Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant.

Participants receive 2 intramuscular doses of Influenza A (H5N1) Virus without adjuvant, administered 21 (+/- 3) days apart.

Intervention Type: BIOLOGICAL

Other Intervention Names

Q-Pan H5N1; adjuvanted Q-Pan H5N1; unadjuvanted H5N1 vaccine

Eligibility Criteria

Inclusion Criteria

• Individuals in good health (as determined by vital signs, medical history, physical examination and laboratory tests);
• Able to understand and give informed consent;
• Women of childbearing potential must agree to practice adequate contraception 1 month prior to study entry and until day 100 of the study.

Exclusion Criteria

• Personal or family history of sleeping disorders including any of the following: Narcolepsy with or without cataplexy; Idiopathic Hypersomnia or excessive daytime sleepiness of unknown origin; Sleep paralysis; Sleep related hallucinations (hypnagogic or hypnopompic hallucinations);
• Human leukocyte antigen (HLA)-DQB1*06:02 positivity (or DQB1*06 positivity if high resolution HLA testing cannot be performed);
• An abnormal erythrocyte sedimentation rate at baseline;
• Receipt of blood products 3 months prior to study entry and until day 100 of the study;
• Volunteers who donated blood 56 days before screening and have plans to donate on or before day 100 of the study;
• Hemoglobin value of less than 12 mg/dL for females and less than 13 mg/dL for males;
• A positive result in the Narcolepsy Mini Screen questionnaire;
• A score of ≥11 on the Epworth sleepiness scale questionnaire;
• Receipt of any experimental agents within 6 weeks prior to first vaccination and until the completion of the study;
• Receipt of any licensed live vaccine within 4 weeks or any licensed inactivated vaccine within 2 weeks prior to the first study vaccination or planned receipt of any vaccine within 42 days after study entry;
• Receipt of a H5 vaccine or AS03-adjuvanted vaccine at any time in the past prior to current study or have a history of A/H5N1 infection;
• Influenza-like illness (ILI) or documented influenza infection during the 2013-2014 influenza season. [Not excluded from the study, volunteers with prior upper respiratory infections other than ILI];
• Chronic medical problems including (but not limited to) insulin dependent diabetes, severe heart disease, severe lung disease, severe liver disease, severe kidney disease, autoimmune disease, severe gastrointestinal disease;
• Alcohol or drug abuse and psychiatric conditions that in the opinion of the investigator would preclude compliance with the trial or interpretation of safety or endpoint data;
• Impaired immune function or chronic infections including (but not limited to) HIV, hepatitis B or C; organ transplant; active cancer or any history of hematologic cancer; receipt of chemotherapy, radiation therapy (past 36 months) or any other potentially immunosuppressive therapy [i.e. Systemic steroids at any dose and intra-articular administration of steroids in the past 3 months; (Nasal and topical steroids are allowed)], congenital immunodeficiency, anatomical or functional asplenia;
• Heart rate less than 40 bpm or greater than 100 bpm. Systolic blood pressure is less than 90 mm Hg or equal or greater than 160 mm Hg. Diastolic blood pressure is less than 60 mm Hg or equal or greater than 100 mg Hg;
• Pregnancy or postpartum (less than 1 year after delivery) or breast feeding;
• Severe reactions to prior vaccination with influenza virus vaccines, including anaphylaxis;
• History of Guillain-Barré syndrome;
• A previous sudden life-threatening allergic reaction to any ingredient of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant or to any of the substances that may be present in trace amounts such as thiomersal, egg residues including ovalbumin as well as residual amounts of sodium deoxycholate detergent, formaldehyde and sucrose;
• Volunteers with any acute illness, including any fever (> 100.4 F [> 38.0 C], regardless of the route) within 3 days prior to study entry;
• Social, occupational, or any other condition that in the opinion of the investigator might interfere with compliance with the study and vaccine evaluation.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Emory University

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nadine Rouphael, MD

Role: PRINCIPAL_INVESTIGATOR

Hope Clinic, Emory University

Locations

The Hope Clinic - Emory Vaccine Center

Decatur, Georgia, United States

Countries

United States

References

Wimmers F, Donato M, Kuo A, Ashuach T, Gupta S, Li C, Dvorak M, Foecke MH, Chang SE, Hagan T, De Jong SE, Maecker HT, van der Most R, Cheung P, Cortese M, Bosinger SE, Davis M, Rouphael N, Subramaniam S, Yosef N, Utz PJ, Khatri P, Pulendran B. The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination. Cell. 2021 Jul 22;184(15):3915-3935.e21. doi: 10.1016/j.cell.2021.05.039. Epub 2021 Jun 25.

Reference Type: DERIVED

PMID: 34174187 (View on PubMed)

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

Other Identifiers

1U19AI090023-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DAIT HIPC: VAX-010

Identifier Type: -

Identifier Source: org_study_id