Influenza HA Ferritin Vaccine, Alone or in Prime-Boost Regimens With an Influenza DNA Vaccine in Healthy Adults

NCT03186781 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 17011017-I-0110
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Influenza, or "flu", is a very common infectious respiratory disease. Researchers want to develop a vaccine against flu. Vaccines teach the body to fight or prevent an infection. When the body learns to fight an infection, this is called an immune response. In this study, researchers want to test two new vaccines to help the body make an immune response to flu. Subjects received the vaccine injections in the upper arm muscle. One vaccine, the influenza HA Ferritin vaccine (HA-F A/Sing), was given to all subjects with a needle injection. The other vaccine, influenza DNA vaccine (DNA A/Sing), was given to subjects in Group 3 by a needle-free device that uses high pressure to push the vaccine through the skin and into the muscle. Objective: To test the safety and side effects of two new vaccines for prevention of H2 influenza (flu). Eligibility: Part I: Healthy adults ages 18-47 born after 1969. Part II: Healthy adults ages 18-70, but not born in 1966-1969. Design: Volunteers were tested for eligibility in a separate screening protocol. In Part I, all subjects received injections of HA Ferritin vaccine. These subjects were not expected to have H2N2 exposure based on their age and when H2N2 last circulated in the population. Five subjects in Group 1 received one injection of 20 mcg dose vaccine at Day 0 to test if it is safe. Then, five additional subjects in Group 2 received a total of two injections of a 60 mcg dose on Day 0 and 16 weeks later. In Part II, responses were evaluated from adults born before 1966 who may have prior potential exposure to H2N2 influenza as well as adults similar to those enrolled in Part I who are not expected to have H2N2 exposure. Also, Part II compared responses to 2 different vaccine regimens. Group 3 subjects received a DNA influenza vaccine prime at Day 0 and the HA Ferritin vaccine boost 16 weeks later. Group 4 subjects received the HA Ferritin vaccine 2 times, on Day 0 and 16 weeks later.

Conditions

Influenza

Keywords

Flu Virus; Flu Shot; H2N2; Protein; Immune Response

Outcome Measures

Primary Outcomes (11)

• Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Each HA-F A/Sing Product Administration

  Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each HA-F A/Sing study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).

  7 days after each HA-F A/Sing product administration, at approximately Week 1 and/or at approximately Week 17

• Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of DNA A/Sing Product Administration

  Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after the DNA A/Sing study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).

  7 days after DNA A/Sing product administration, at approximately Week 1

• Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Each HA-F A/Sing Product Administration

  Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each HA-F A/Sing study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).

  7 days after each HA-F A/Sing product administration, at approximately Week 1 and/or at approximately Week 17

• Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of DNA A/Sing Product Administration

  Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after DNA A/Sing study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).

  7 days after DNA A/Sing product administration, at approximately Week 1

• Number of Subjects With Abnormal Laboratory Measures of Safety

  Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety laboratory parameters included hematology (hemoglobin, hematocrit, platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil percents/counts) and chemistry (alanine aminotransferase (ALT), alanine aspartate (AST), alkaline phosphate (ALP), creatinine and total bilirubin). Complete blood count (CBC) with differential, total bilirubin, AST, ALT, and ALP results were collected at screening (≤ 84 days before enrollment), Day 0 prior to study product administration (baseline), and at Days 14, 28, 112, 140 and 280. Creatinine results were collected at screening, Day 0 and Day 6. Institutional laboratory normal ranges as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.

  Day 0 through Day 280

• Number of Subjects With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Each HA-F A/Sing Product Administration

  Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the visit scheduled for 4 weeks after each study product administration. At other time periods between study product administrations and when greater than 4 weeks after the last study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module), influenza-like illness (ILI) or influenza (reported as a separate outcome) and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 through 4 weeks after each HA-F A/Sing product administration, up to Week 20

• Number of Subjects With One or More Unsolicited Non-Serious Adverse Events (AEs) Following DNA A/Sing Product Administration

  Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the visit scheduled for 4 weeks after each study product administration. At other time periods between study product administrations and when greater than 4 weeks after the last study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module), influenza-like illness (ILI) or influenza (reported as a separate outcome) and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 through 4 weeks after DNA A/Sing product administration, up to Week 4

• Number of Subjects With Influenza or Influenza-like Illness (ILIs) Following HA-F A/Sing Product Administration

  Influenza or influenza-like illness (ILI) were recorded in the study database from receipt of the first study product administration through the last study visit.

  Day 0 through Day 280

• Number of Subjects With Influenza or Influenza-like Illness (ILIs) Following DNA A/Sing Product Administration

  Influenza or influenza-like illness (ILI) were recorded in the study database from receipt of the first study product administration through the last study visit.

  Day 0 through Day 280

• Number of Subjects With Serious Adverse Events (SAEs) Following HA-F A/Sing Product Administration

  SAEs were recorded from receipt of first study product administration through the last expected study visit at Day 280. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 through Day 280

• Number of Subjects With Serious Adverse Events (SAEs) Following DNA A/Sing Product Administration

  SAEs were recorded from receipt of first study product administration through the last expected study visit at Day 280. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 through Day 280

Secondary Outcomes (3)

• Hemagglutination Inhibition Assay (HAI) Geometric Mean Titer (GMT) Against A/Singapore/1/1957 (H2N2) Following the Completion of Each Vaccine Regimen

  Four weeks after the first dose for groups that received a single vaccination, at Week 4 or two weeks after the second dose for groups that received two vaccinations, at Week 18

• Pseudoviral Neutralization Assay Geometric Mean Titer (GMT) Against A/Singapore/1/1957 (H2N2) Following the Completion of Each Vaccine Regimen

  Four weeks after the first dose for groups that received a single vaccination, at Week 4 or two weeks after the second dose for groups that received two vaccinations, at Week 18

• Seroconversion Rate Following the Completion of Each Vaccine Regimen

  Four weeks after the first dose for groups that received a single vaccination, at Week 4 or two weeks after the second dose for groups that received two vaccinations, at Week 18

Study Arms (6)

Group 1: HA-F A/Sing (20 mcg), ages 18-47 Yrs

EXPERIMENTAL

HA-F A/Sing injections (20 mcg) administered intramuscularly (IM) by Needle/Syringe (Day 0) in H2-naïve adults (adults with no pre-existing immunity to H2)

Biological: VRC-FLUNPF081-00-VP (HA-F A/Sing)

Group 2: HA-F A/Sing (60 mcg), ages 18-47 Yrs

EXPERIMENTAL

HA-F A/Sing injections (60 mcg) administered IM by Needle/Syringe (Day 0 and Week 16) in H2-naïve adults (adults with no pre-existing immunity to H2)

Biological: VRC-FLUNPF081-00-VP (HA-F A/Sing)

Group 3A: DNA A/Sing(4 mg)-HA-F A/Sing(60 mcg), ages 18-47 Yrs

EXPERIMENTAL

DNA A/Sing injections (4 mg) administered IM by PharmaJet (Day 0); HA-F A/Sing injections (60 mcg) administered IM by Needle/Syringe (Week 16) in H2-naïve adults (adults with no pre-existing immunity to H2)

Biological: VRC-FLUNPF081-00-VP (HA-F A/Sing); Biological: VRC-FLUDNA082-00-VP (DNA A/Sing)

Group 3B: DNA A/Sing(4 mg)-HA-F A/Sing(60 mcg), ages 52-70 Yrs

EXPERIMENTAL

DNA A/Sing injections (4 mg) administered IM by PharmaJet (Day 0); HA-F A/Sing injections (60 mcg) administered IM by Needle/Syringe (Week 16) in H2-exposed adults (may have some H2 immunity)

Biological: VRC-FLUNPF081-00-VP (HA-F A/Sing); Biological: VRC-FLUDNA082-00-VP (DNA A/Sing)

Group 4A: HA-F A/Sing (60 mcg), ages 18-47 Yrs

EXPERIMENTAL

HA-F A/Sing injections (60 mcg) administered IM by Needle/Syringe (Day 0 and Week 16) in H2-naïve adults (adults with no pre-existing immunity to H2)

Biological: VRC-FLUNPF081-00-VP (HA-F A/Sing)

Group 4B: HA-F A/Sing (60 mcg), ages 52-70 Yrs

EXPERIMENTAL

HA-F A/Sing injections (60 mcg) administered IM by Needle/Syringe (Day 0 and Week 16) in H2-exposed adults (may have some H2 immunity)

Biological: VRC-FLUNPF081-00-VP (HA-F A/Sing)

Interventions

VRC-FLUNPF081-00-VP (HA-F A/Sing) BIOLOGICAL

VRC-FLUNPF081-00-VP (HA-F A/Sing) is an investigational influenza HA ferritin vaccine.

Group 1: HA-F A/Sing (20 mcg), ages 18-47 Yrs; Group 2: HA-F A/Sing (60 mcg), ages 18-47 Yrs; Group 3A: DNA A/Sing(4 mg)-HA-F A/Sing(60 mcg), ages 18-47 Yrs; Group 3B: DNA A/Sing(4 mg)-HA-F A/Sing(60 mcg), ages 52-70 Yrs; Group 4A: HA-F A/Sing (60 mcg), ages 18-47 Yrs; Group 4B: HA-F A/Sing (60 mcg), ages 52-70 Yrs

VRC-FLUDNA082-00-VP (DNA A/Sing) BIOLOGICAL

VRC-FLUDNA082-00-VP (DNA A/Sing) is an investigational influenza plasmid DNA vaccine.

Group 3A: DNA A/Sing(4 mg)-HA-F A/Sing(60 mcg), ages 18-47 Yrs; Group 3B: DNA A/Sing(4 mg)-HA-F A/Sing(60 mcg), ages 52-70 Yrs

Eligibility Criteria

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

You may qualify if:

• A subject must meet all of the following criteria:
• Healthy subjects aged 18-70 (excluding subjects born between 1966-1969)

You may not qualify if:

• Received at least one licensed current seasonal influenza vaccine from 2014 to the present
• Able and willing to complete the informed consent process
• Available for clinic visits for 40 weeks after enrollment
• Willing to have blood samples collected, stored indefinitely, and used for research purposes
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
• Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) less than or equal to 40 within the 84 days before enrollment
• Laboratory Criteria within 84 days before enrollment:
• White blood cells (WBC) and differential either within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval
• Total lymphocyte count greater than or equal to 800 cells/mm\^3
• Platelets = 125,000 - 500,000/mm\^3
• Hemoglobin within institutional normal range
• Serum iron either within institutional normal range or accompanied by the site PI or designee approval
• Alanine aminotransferase (ALT) less than or equal to 1.25 times institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) less than or equal to 1.25 times institutional ULN
• Alkaline phosphatase (ALP) less than or equal to 1.1 times institutional ULN

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Kanekiyo M, Wei CJ, Yassine HM, McTamney PM, Boyington JC, Whittle JR, Rao SS, Kong WP, Wang L, Nabel GJ. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. 2013 Jul 4;499(7456):102-6. doi: 10.1038/nature12202. Epub 2013 May 22.

  PMID: 23698367 BACKGROUND

• Yamashita I, Iwahori K, Kumagai S. Ferritin in the field of nanodevices. Biochim Biophys Acta. 2010 Aug;1800(8):846-57. doi: 10.1016/j.bbagen.2010.03.005. Epub 2010 Mar 12.

  PMID: 20227466 BACKGROUND

• Nabel GJ, Wei CJ, Ledgerwood JE. Vaccinate for the next H2N2 pandemic now. Nature. 2011 Mar 10;471(7337):157-8. doi: 10.1038/471157a. No abstract available.

  PMID: 21390107 BACKGROUND

• Andrews SF, Raab JE, Gorman J, Gillespie RA, Cheung CSF, Rawi R, Cominsky LY, Boyington JC, Creanga A, Shen CH, Harris DR, Olia AS, Nazzari AF, Zhou T, Houser KV, Chen GL, Mascola JR, Graham BS, Kanekiyo M, Ledgerwood JE, Kwong PD, McDermott AB. A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination. Nat Med. 2022 Feb;28(2):373-382. doi: 10.1038/s41591-021-01636-8. Epub 2022 Feb 3.

  PMID: 35115707 DERIVED

• Houser KV, Chen GL, Carter C, Crank MC, Nguyen TA, Burgos Florez MC, Berkowitz NM, Mendoza F, Hendel CS, Gordon IJ, Coates EE, Vazquez S, Stein J, Case CL, Lawlor H, Carlton K, Gaudinski MR, Strom L, Hofstetter AR, Liang CJ, Narpala S, Hatcher C, Gillespie RA, Creanga A, Kanekiyo M, Raab JE, Andrews SF, Zhang Y, Yang ES, Wang L, Leung K, Kong WP, Freyn AW, Nachbagauer R, Palese P, Bailer RT, McDermott AB, Koup RA, Gall JG, Arnold F, Mascola JR, Graham BS, Ledgerwood JE; VRC 316 Study Team. Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial. Nat Med. 2022 Feb;28(2):383-391. doi: 10.1038/s41591-021-01660-8. Epub 2022 Feb 3.

  PMID: 35115706 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Martin Gaudinski, MD
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

martin.gaudinski@nih.gov

301-451-8715

Study Officials

• Grace L Chen, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 14, 2017
• Study Start: October 25, 2017
• Primary Completion: September 3, 2019
• Study Completion: September 3, 2019
• Last Updated: June 16, 2021
• Results First Posted: October 19, 2020

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)