Dose, Safety, Tolerability and Immunogenicity of an Influenza H10 Stabilized Stem Ferritin Vaccine, VRC-FLUNPF0103-00-VP, in Healthy Adults

NCT04579250 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 20014520-I-0145
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The flu is a common viral infection that can be deadly for certain people. Vaccines against flu have been developed to teach the body to prevent or fight the infection. A new vaccine may help the body to make an immune response to H10 flu, a flu strain that infects humans. Objective: To test the safety and effectiveness of the H10 Stabilized Stem Ferritin vaccine (VRC-FLUNPF0103-00-VP or H10ssF-6473). Eligibility: Healthy adults ages 18-70, but not born between 1965-1970 Design: Participants received 1 or 2 vaccinations by injections (shots) in the upper arm muscle over 4 months. Participants received a thermometer and recorded their temperature and symptoms every day on/with/via a diary card for 7 days after each injection. The injection site was checked for redness, swelling, itching or bruising. Participants had 8-10 follow-up visits over 10 months. At follow-up visits, participants had blood drawn and were checked for health changes or problems. Participants who reported influenza-like illness had nose and throat swabs collected for evaluation of viral infection. Some participants had apheresis. A needle was placed into a vein in both arms. Blood was removed through a needle in the vein of one arm. A machine removed the white blood cells and then the rest of the blood was returned to the participant through a needle in the other arm.

Conditions

Influenza

Keywords

Flu Virus; Respiratory Illness; Viral Infection; Experimental Vaccine

Outcome Measures

Primary Outcomes (7)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Each H10ssF-6473 Product Administration

  Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants 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 participants 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, modified from FDA Guidance - September 2007.

  7 days after each H10ssF-6473 product administration, at approximately Week 1 and at approximately Week 17

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Each H10ssF-6473 Product Administration

  Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants 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 participants 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, modified from FDA Guidance - September 2007.

  7 days after each H10ssF-6473 product administration, at approximately Week 1 and at approximately Week 17

• Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following H10ssF-6473 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 and new chronic medical conditions that required ongoing medical management (reported as separate outcomes) 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 participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 through 4 weeks after each H10ssF-6473 product administration, up to Week 20

• Number of Participants With Serious Adverse Events (SAEs) Following H10ssF-6473 Product Administration

  SAEs were recorded from receipt of first study product administration through the last expected study visit at Week 40. 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 participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40

• Number of Participants With Influenza or Influenza-like Illness (ILIs) Following H10ssF-6473 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. ILI was defined as fever (temperature of 100 degrees F \[37.8 degrees C\] or greater) and a cough and/or sore throat in the absence of a known cause other than influenza. Collection of nasopharyngeal swabs were used for laboratory confirmation of influenza by polymerase chain reaction (PCR) in participants who met criteria for ILI. Subsequently, results of any reported laboratory testing for identification of pathogens were included for cases meeting initial criteria for ILI. The severity of illness in participants with laboratory confirmed influenza illness were captured on a case report form rather than on an Adverse Event (AE) form.

  Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40

• Number of Participants With New Chronic Medical Conditions Following H10ssF-6473 Product Administration

  New chronic medical conditions that required ongoing medical management were recorded from receipt of first study product administration through the last expected study visit at Week 40. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40

• Number of Participants With Abnormal Laboratory Measures of Safety Following H10ssF-6473 Product Administration

  Abnormal lab results recorded as unsolicited adverse events (AEs) are summarized. Safety lab 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 Day 14, 28, and 280 (Group 1) or at Day 14, 28, 112, 140 and 280 (Groups 2A-2B). Iron and serum ferritin were collected at Day 28 (Group 1) or at Days 112 and 140 (Groups 2A-2B). Creatinine results were collected at Day 14 (Group 1) or at Days 14 and 140 (Groups 2A-2B). Institutional lab normal ranges as well as Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.

  Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40

Secondary Outcomes (1)

• Stem-Specific Antibody Response to H10ssF-6473 Following the Completion of Each Vaccination Regimen

  Baseline to 2 weeks after the single or first injection, at Week 2 and from Week 16 to 2 weeks after the second injection, at Week 18

Study Arms (3)

Group 1: H10ssF-6473 (20 mcg), ages 18-50 years

EXPERIMENTAL

H10ssF-6473 (20 mcg) administered intramuscularly (IM) by Needle/Syringe (Day 0)

Biological: VRC-FLUNPF0103-00-VP (H10ssF-6473)

Group 2A: H10ssF-6473 (60 mcg), ages 18-50 years

EXPERIMENTAL

H10ssF-6473 (60 mcg) administered IM by Needle/Syringe (Day 0 and Week 16)

Biological: VRC-FLUNPF0103-00-VP (H10ssF-6473)

Group 2B: H10ssF-6473 (60 mcg), ages 55-70 years

EXPERIMENTAL

H10ssF-6473 (60 mcg) administered IM by Needle/Syringe (Day 0 and Week 16)

Biological: VRC-FLUNPF0103-00-VP (H10ssF-6473)

Interventions

VRC-FLUNPF0103-00-VP (H10ssF-6473) BIOLOGICAL

The vaccine is composed of the haemagglutinin (HA) stem domain from A/Jiangxi/IPB13/2013 (H10N8) influenza genetically fused to the ferritin protein from H. pylori. Purified H10ssF-6473 displays eight well-formed HA trimers that antigenically resemble the native H10 stem viral spikes.

Group 1: H10ssF-6473 (20 mcg), ages 18-50 years; Group 2A: H10ssF-6473 (60 mcg), ages 18-50 years; Group 2B: H10ssF-6473 (60 mcg), ages 55-70 years

Eligibility Criteria

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

You may qualify if:

• Healthy adults between the ages of 18-70 years (excluding adults born between January 1, 1965 and December 31,1970)

You may not qualify if:

• Received at least one licensed influenza vaccine from 2015 to the present
• Able and willing to complete the informed consent process
• Available for clinic visits for 40 weeks after enrollment
• 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 56 days before enrollment
• Laboratory Criteria within 56 days before enrollment
• White blood cells (WBC) and differential 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/microL
• Platelets = 125,000 - 500,000 cells/microL
• Hemoglobin within institutional normal range or accompanied by the PI or designee approval
• Serum iron within institutional normal range or accompanied by the site PI or designee approval
• Serum ferritin within institutional normal range or accompanied by the site PI or designee approval
• Alanine aminotransferase (ALT) less than or equal to 1.25 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) less than or equal to 1.25 x institutional ULN
• Alkaline phosphatase (ALP) \<1.1 x 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 (4)

• Ledgerwood JE, Zephir K, Hu Z, Wei CJ, Chang L, Enama ME, Hendel CS, Sitar S, Bailer RT, Koup RA, Mascola JR, Nabel GJ, Graham BS; VRC 310 Study Team. Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect. J Infect Dis. 2013 Aug 1;208(3):418-22. doi: 10.1093/infdis/jit180. Epub 2013 Apr 30.

  PMID: 23633407 BACKGROUND

• 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

• Boyoglu-Barnum S, Hutchinson GB, Boyington JC, Moin SM, Gillespie RA, Tsybovsky Y, Stephens T, Vaile JR, Lederhofer J, Corbett KS, Fisher BE, Yassine HM, Andrews SF, Crank MC, McDermott AB, Mascola JR, Graham BS, Kanekiyo M. Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses. Nat Commun. 2020 Feb 7;11(1):791. doi: 10.1038/s41467-020-14579-4.

  PMID: 32034141 BACKGROUND

• 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 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Influenza, Human; Virus Diseases

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: VRC Clinical Trials Program Leadership
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

ctpleadership@mail.nih.gov

301-451-8715

Study Officials

• Joseph P Casazza, 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: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Dose escalation study

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: October 8, 2020
• Study Start: October 8, 2020
• Primary Completion: January 27, 2022
• Study Completion: January 27, 2022
• Last Updated: February 22, 2023
• Results First Posted: February 22, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)