Seasonal Influenza HA DNA With Trivalent Inactivated Vaccine (TIV) Administered ID or IM in Healthy Adults 18-70 Years

NCT ID: NCT01676402

Last Updated: 2022-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 316 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2014-04-30

Brief Summary

This is a Phase Ib study in healthy adults (18-70 years) to evaluate the safety, tolerability, and immunogenicity of same season and sequential season vaccination schedules consisting of the 2012/2013 seasonal influenza DNA vaccine (HA DNA) and licensed trivalent influenza vaccine (TIV) administered intradermally (ID) or intramuscularly (IM). The hypothesis is that evaluation of these investigational schedules will inform development of novel influenza vaccine strategies that may offer improved and cross-protective immunity against antigenically diverse influenza strains.

Detailed Description

Vaccines are an effective way to prevent influenza infection. Each year the World Health Organization (WHO) and the U.S FDA recommend the influenza strains to include in the seasonal influenza vaccines. The licensed seasonal influenza vaccines are directed against 3 influenza virus strains: an influenza A H1N1, an influenza A H3N2, and an influenza B. The currently approved vaccines depend upon labor-intensive methods that limit manufacturing speed and capacity. Influenza vaccines that can be more rapidly produced and that induce stronger, broader and more persistent immune responses are a recognized public health need.

In this protocol we propose to use DNA vaccine antigen delivery to induce immune responses against native hemagglutinin (HA) structures prior to boosting with licensed TIV ID or with TIV IM.

The study will allow evaluation of the safety and immunogenicity of same season and sequential season vaccination schedules. The same season regimens (2012/13 prime and boost with a 14 week interval) consist of HA DNA prime with TIV ID boost -- or -- HA DNA prime with TIV IM boost. The active comparator for these schedules are TIV ID or TIV IM alone because a single dose of TIV is the standard for adult influenza vaccination within a single season. The sequential season regimens (2012/13 prime and 2013/14 boost) consist of concurrent administration (in different arms) of HA DNA and TIV ID prime with TIV ID boost -- or -- HA DNA and TIV IM prime with TIV IM boost. The active comparator for these regimens will be TIV ID followed by TIV ID boost -- or -- TIV IM followed by TIV IM boost, administered sequential seasons consistent with as typical pattern of use for these licensed vaccines. Evaluation of the investigational schedules and active comparator schedules will inform development of novel influenza vaccine strategies that may offer improved and cross-protective immunity against diverse influenza strains.

Conditions

Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1: HA DNA + TIV ID

2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV ID at Week 14±2 wks

Group Type: EXPERIMENTAL

Seasonal Influenza DNA vaccine

Intervention Type: BIOLOGICAL

VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 4 mg dosage is administered as a 1 mL volume.

TIV

Intervention Type: BIOLOGICAL

2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Group 2: HA DNA + TIV IM

2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV IM at Week 14±2 wks

Group Type: EXPERIMENTAL

Seasonal Influenza DNA vaccine

Intervention Type: BIOLOGICAL

VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 4 mg dosage is administered as a 1 mL volume.

TIV

Intervention Type: BIOLOGICAL

2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Group 3: TIV ID + TIV ID

licensed 2012/13 TIV ID at Day 0 and licensed 2013/14 TIV ID at Week 44±2 weeks

Group Type: EXPERIMENTAL

TIV

Intervention Type: BIOLOGICAL

2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Group 4: TIV IM + TIV IM

2012/13 licensed TIV IM at Day 0 and licensed 2013/14 TIV IM at Week 44±2 weeks

Group Type: EXPERIMENTAL

TIV

Intervention Type: BIOLOGICAL

2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Group 5: (HA DNA and TIV ID) + TIV ID

2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) and licensed 2012/13 TIV ID at Day 0 followed by licensed 2013/14 TIV ID at Week 44±2 weeks

Group Type: EXPERIMENTAL

Seasonal Influenza DNA vaccine

Intervention Type: BIOLOGICAL

VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 4 mg dosage is administered as a 1 mL volume.

TIV

Intervention Type: BIOLOGICAL

2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Group 6: (HA DNA and TIV IM) + TIV IM

2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) and licensed 2012/13 TIV IM at Day 0 followed by licensed 2013/14 TIV IM at Week 44±2 weeks

Group Type: EXPERIMENTAL

Seasonal Influenza DNA vaccine

Intervention Type: BIOLOGICAL

VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 4 mg dosage is administered as a 1 mL volume.

TIV

Intervention Type: BIOLOGICAL

2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Interventions

Seasonal Influenza DNA vaccine

VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 4 mg dosage is administered as a 1 mL volume.

Intervention Type: BIOLOGICAL

TIV

2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Intervention Type: BIOLOGICAL

Other Intervention Names

VRC-FLUDNA063-00-VP; HA DNA Vaccine; Seasonal influenza trivalent DNA vaccine; 2012/13 Seasonal Influenza TIV (Fluzone); 2013/14 Seasonal Influenza TIV (Fluzone)

Eligibility Criteria

Inclusion Criteria

A subject must meet all of the following criteria:

• Healthy adults, 18 to 70 years old; volunteers who will be older than 64 during the 2013/2014 influenza season will not be enrolled after 11/16/2012.
• Available for clinical follow-up
• Able and willing to complete the informed consent process
• Willing to donate blood for sample storage to be used for future research
• Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) ≤40 within the 70 days prior to enrollment
• Has not yet received the current year (2012/13) influenza vaccine prior to enrollment and agrees to receive seasonal influenza vaccines during study participation only from the study site

Laboratory Criteria within 70 days prior to enrollment:

• Hemoglobin within institutional normal limits
• White blood cells either within institutional normal range or accompanied by site physician approval as consistent with healthy adult status
• Platelets = 125,000 - 500,000/mm3
• Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Serum creatinine ≤ 1 x ULN based on site institutional normal range

Criteria applicable to women of childbearing potential:

• Negative human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of enrollment
• Agree to use an effective means of birth control from 21 days prior to enrollment through 3 weeks after the second study vaccination

Exclusion Criteria

A subject will be excluded if one or more of the following conditions apply:

Women Specific:

• Breast-feeding or planning to become pregnant while participating in the study

Subject has received any of the following substances:

• More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 12 weeks prior to enrollment or any within the 14 days prior to enrollment
• Blood products within 16 weeks prior to enrollment
• Immunoglobulin within 8 weeks prior to enrollment
• Investigational research agents within 28 days (4 weeks) prior to enrollment or planning to receive investigational products while on the study.
• Allergy treatment with antigen injections, unless on maintenance schedule and allergy shots could be staggered with the study vaccinations, within 14 days (2 weeks) prior to enrollment
• Current anti-tuberculosis (TB) prophylaxis or therapy

Subject has a history of any of the following clinically significant conditions:

• Contraindication to receiving an FDA-approved seasonal influenza vaccination
• Serious reactions to vaccines that preclude receipt of study vaccinations, as determined by the site investigator
• Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema
• Asthma that is severe, unstable or required emergent care, urgent care, hospitalization or intubation during the previous two years or that is expected to require the use of oral, intravenous or high dose inhaled corticosteroids
• Diabetes mellitus type I
• Thyroid disease that is not well-controlled
• Generalized idiopathic urticaria within the 1 year prior to enrollment
• Hypertension that is not well controlled
• Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions), or significant bruising or bleeding difficulties with IM injections or blood draws, or use of blood thinners such as Coumadin or Plavix®
• Malignancy that is active or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of the study
• Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures for which no treatment has been required within the 3 years prior to enrollment
• Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
• Guillain-Barré Syndrome
• Psychiatric condition that precludes compliance with the protocol; past or present psychoses; disorder requiring lithium; or within 5 years prior to enrollment, a history of suicide plan or attempt
• Any medical, psychiatric, or other condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs ability to give informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barney S Graham, M.D., Ph.D.

Role: STUDY_DIRECTOR

Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH

Julie Ledgerwood, DO

Role: STUDY_CHAIR

Deputy Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH

Locations

Stanford University School of Medicine

Stanford, California, United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Saint Louis University - Doisy Research Center

St Louis, Missouri, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

Ledgerwood JE, Wei CJ, Hu Z, Gordon IJ, Enama ME, Hendel CS, McTamney PM, Pearce MB, Yassine HM, Boyington JC, Bailer R, Tumpey TM, Koup RA, Mascola JR, Nabel GJ, Graham BS; VRC 306 Study Team. DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials. Lancet Infect Dis. 2011 Dec;11(12):916-24. doi: 10.1016/S1473-3099(11)70240-7. Epub 2011 Oct 3.

Reference Type: BACKGROUND

PMID: 21975270 (View on PubMed)

Ledgerwood JE, Graham BS. DNA vaccines: a safe and efficient platform technology for responding to emerging infectious diseases. Hum Vaccin. 2009 Sep;5(9):623-6. doi: 10.4161/hv.8627. No abstract available.

Reference Type: BACKGROUND

PMID: 19779298 (View on PubMed)

Carter C, Houser KV, Yamshchikov GV, Bellamy AR, May J, Enama ME, Sarwar U, Larkin B, Bailer RT, Koup R, Chen GL, Patel SM, Winokur P, Belshe R, Dekker CL, Graham BS, Ledgerwood JE; VRC 703 study team. Safety and immunogenicity of investigational seasonal influenza hemagglutinin DNA vaccine followed by trivalent inactivated vaccine administered intradermally or intramuscularly in healthy adults: An open-label randomized phase 1 clinical trial. PLoS One. 2019 Sep 18;14(9):e0222178. doi: 10.1371/journal.pone.0222178. eCollection 2019.

Reference Type: RESULT

PMID: 31532789 (View on PubMed)

Other Identifiers

VRC 703

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

VRC 703

Identifier Type: -

Identifier Source: org_study_id