Dose, Safety, Tolerability and Immunogenicity of an Influenza H1 Stabilized Stem Ferritin Vaccine in Healthy Adults

Study at a glance

From the registry record, last updated by the sponsor on 29 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

VRC 321: A Phase I Open-Label Clinical Trial to Evaluate Dose, Safety, Tolerability, and Immunogenicity of an Influenza H1 Stabilized Stem Ferritin Vaccine, VRCFLUNPF099-00-VP, in Healthy Adults

ClinicalTrials.gov ID

NCT03814720

Acronym / sponsor ID

190032

Conditions

Influenza Infection

Keywords

Flu, Seasonal Allergy, Respiratory Illness, Flu Virus, Viral Infection

Phase

Phase 1

Study type

Interventional

Recruitment status

Completed

Enrolment

52 participants (actual)

Lead sponsor

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

Study start

1 Apr 2019 (actual)

Primary completion

6 Apr 2021 (actual)

Study completion

6 Apr 2021 (actual)

First posted

24 Jan 2019 (actual)

Results

Posted 29 Apr 2022

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

Randomised

Intervention model

Sequential

Masking

None (open label)

Number of arms

5

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 H1ssF_3928 Product Administration

   Time frame: 7 days after each H1ssF_3928 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 H1ssF_3928 Product Administration

   Time frame: 7 days after each H1ssF_3928 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 H1ssF_3928 Product Administration

   Time frame: Day 0 through 4 weeks after each H1ssF_3928 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 H1ssF_3928 Product Administration

   Time frame: Day 0 through the study participation, up to Week 68

   SAEs were recorded from receipt of first study product administration through the last expected study visit at Week 68. 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 H1ssF_3928 Product Administration

   Time frame: Day 0 through the study participation, up to Week 68

   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.

6. Number of Participants With New Chronic Medical Conditions Following H1ssF_3928 Product Administration

   Time frame: Day 0 through the study participation, up to Week 68

   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 68. 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 H1ssF_3928 Product Administration

   Time frame: Day 0 through the study participation, up to Week 68

   Any abnormal laboratory results recorded after product administration 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 Days 14, 28, 280, 364 and 476. Iron and serum ferritin were collected at Day 28. Creatinine results were collected at Day 14. 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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2022.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Background: PubMed 25007847Krammer F, Palese P, Steel J. Advances in universal influenza virus vaccine design and antibody mediated therapies based on conserved regions of the hemagglutinin. Curr Top Microbiol Immunol. 2015;386:301-21. doi: 10.1007/82_2014_408.
• 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 26301691Yassine HM, Boyington JC, McTamney PM, Wei CJ, Kanekiyo M, Kong WP, Gallagher JR, Wang L, Zhang Y, Joyce MG, Lingwood D, Moin SM, Andersen H, Okuno Y, Rao SS, Harris AK, Kwong PD, Mascola JR, Nabel GJ, Graham BS. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med. 2015 Sep;21(9):1065-70. doi: 10.1038/nm.3927. Epub 2015 Aug 24.
• Derived from this study: PubMed 37075129Widge AT, Hofstetter AR, Houser KV, Awan SF, Chen GL, Burgos Florez MC, Berkowitz NM, Mendoza F, Hendel CS, Holman LA, Gordon IJ, Apte P, Liang CJ, Gaudinski MR, Coates EE, Strom L, Wycuff D, Vazquez S, Stein JA, Gall JG, Adams WC, Carlton K, Gillespie RA, Creanga A, Crank MC, Andrews SF, Castro M, Serebryannyy LA, Narpala SR, Hatcher C, Lin BC, O'Connell S, Freyn AW, Rosado VC, Nachbagauer R, Palese P, Kanekiyo M, McDermott AB, Koup RA, Dropulic LK, Graham BS, Mascola JR, Ledgerwood JE; VRC 321 study team. An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults. Sci Transl Med. 2023 Apr 19;15(692):eade4790. doi: 10.1126/scitranslmed.ade4790. Epub 2023 Apr 19.
• Derived from this study: PubMed 37075126Andrews SF, Cominsky LY, Shimberg GD, Gillespie RA, Gorman J, Raab JE, Brand J, Creanga A, Gajjala SR, Narpala S, Cheung CSF, Harris DR, Zhou T, Gordon I, Holman L, Mendoza F, Houser KV, Chen GL, Mascola JR, Graham BS, Kwong PD, Widge A, Dropulic LK, Ledgerwood JE, Kanekiyo M, McDermott AB. An influenza H1 hemagglutinin stem-only immunogen elicits a broadly cross-reactive B cell response in humans. Sci Transl Med. 2023 Apr 19;15(692):eade4976. doi: 10.1126/scitranslmed.ade4976. Epub 2023 Apr 19.
• 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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