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

Study at a glance

From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

VRC 323: A Phase I Open-Label Clinical Trial to Evaluate the Dose, Safety, Tolerability and Immunogenicity of an Influenza H10 Stabilized Stem Ferritin Vaccine, VRC-FLUNPF0103-00-VP, in Healthy Adults

ClinicalTrials.gov ID

NCT04579250

Acronym / sponsor ID

200145

Conditions

Influenza

Keywords

Flu Virus, Respiratory Illness, Viral Infection, Experimental Vaccine

Phase

Phase 1

Study type

Interventional

Recruitment status

Completed

Enrolment

25 participants (actual)

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health

Study start

8 Oct 2020 (actual)

Primary completion

27 Jan 2022 (actual)

Study completion

27 Jan 2022 (actual)

First posted

8 Oct 2020 (actual)

Results

Posted 22 Feb 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Prevention

Allocation

Non-randomised

Intervention model

Sequential

Masking

None (open label)

Number of arms

3

Model description

Dose escalation study

Who may qualify

Ages

18 to 70 years

Sex

All

Healthy volunteers

Accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

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

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

   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.

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

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

   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.

3. Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following H10ssF-6473 Product Administration

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

   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.

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

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

   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.

5. Number of Participants With Influenza or Influenza-like Illness (ILIs) Following H10ssF-6473 Product Administration

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

   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.

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

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

   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.

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

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

   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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Background: PubMed 23633407Ledgerwood 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.
• Background: PubMed 23698367Kanekiyo 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.
• Background: PubMed 32034141Boyoglu-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.
• Background: PubMed 35115706Houser 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.
• NIH Clinical Center Detailed Web PageLink provided by the sponsor.
• Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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