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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03814720
Recruitment Status : Completed
First Posted : January 24, 2019
Results First Posted : April 29, 2022
Last Update Posted : April 29, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

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 H1 flu, a flu strain that infects humans.

Objective:

To test the safety and effectiveness of the H1 Stabilized Stem Ferritin vaccine (VRC-FLUNPF099-00-VP).

Eligibility:

Healthy people ages 18-70 years old who got at least 1 licensed flu vaccine since January 1, 2014.

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 a diary card for 7 days after each injection. The injection site was checked for redness, swelling, or bruising.

Participants had 9-11 follow-up visits over 12-15 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 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.

A separate consent was provided to participants for genetic testing on their samples.


Condition or disease Intervention/treatment Phase
Influenza Infection Biological: VRC-FLUNPF099-00-VP (H1ssF_3928) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : April 1, 2019
Actual Primary Completion Date : April 6, 2021
Actual Study Completion Date : April 6, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot Vaccines

Arm Intervention/treatment
Experimental: Group 1: H1ssF_3928 (20 mcg), ages 18-40 years
H1ssF_3928 (20 mcg) administered intramuscularly (IM) by Needle/Syringe (Day 0)
Biological: VRC-FLUNPF099-00-VP (H1ssF_3928)
The vaccine is composed of the HA stem domain from Influenza A/New Caledonia/20/1999 (H1N1) genetically fused to the ferritin protein from H. pylori. Purified H1ssF_3928 particles display eight well-formed HA trimers that antigenically resemble the native H1 stem viral spikes.

Experimental: Group 2A: H1ssF_3928 (60 mcg), ages 18-40 years
H1ssF_3928 (60 mcg) administered IM by Needle/Syringe (Day 0 and Week 16)
Biological: VRC-FLUNPF099-00-VP (H1ssF_3928)
The vaccine is composed of the HA stem domain from Influenza A/New Caledonia/20/1999 (H1N1) genetically fused to the ferritin protein from H. pylori. Purified H1ssF_3928 particles display eight well-formed HA trimers that antigenically resemble the native H1 stem viral spikes.

Experimental: Group 2B: H1ssF_3928 (60 mcg), ages 41-49 years
H1ssF_3928 (60 mcg) administered IM by Needle/Syringe (Day 0 and Week 16)
Biological: VRC-FLUNPF099-00-VP (H1ssF_3928)
The vaccine is composed of the HA stem domain from Influenza A/New Caledonia/20/1999 (H1N1) genetically fused to the ferritin protein from H. pylori. Purified H1ssF_3928 particles display eight well-formed HA trimers that antigenically resemble the native H1 stem viral spikes.

Experimental: Group 2C: H1ssF_3928 (60 mcg), ages 50-59 years
H1ssF_3928 (60 mcg) administered IM by Needle/Syringe (Day 0 and Week 16)
Biological: VRC-FLUNPF099-00-VP (H1ssF_3928)
The vaccine is composed of the HA stem domain from Influenza A/New Caledonia/20/1999 (H1N1) genetically fused to the ferritin protein from H. pylori. Purified H1ssF_3928 particles display eight well-formed HA trimers that antigenically resemble the native H1 stem viral spikes.

Experimental: Group 2D: H1ssF_3928 (60 mcg), ages 60-70 years
H1ssF_3928 (60 mcg) administered IM by Needle/Syringe (Day 0 and Week 16)
Biological: VRC-FLUNPF099-00-VP (H1ssF_3928)
The vaccine is composed of the HA stem domain from Influenza A/New Caledonia/20/1999 (H1N1) genetically fused to the ferritin protein from H. pylori. Purified H1ssF_3928 particles display eight well-formed HA trimers that antigenically resemble the native H1 stem viral spikes.




Primary Outcome Measures :
  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.


Secondary Outcome Measures :
  1. Pseudoviral Neutralization Assay Geometric Mean Titer (GMT) Against Homologous A/New Caledonia/20/1999 Virus (H1N1) Following the Completion of Each Vaccination Regimen [ Time Frame: Baseline to 2 weeks after 1st dose for participants who received a single injection, at Week 2 or From Baseline to 2 weeks after 1st dose and from Week 16 to 2 weeks after 2nd dose for participants who received two injections, at Weeks 2 and 18 ]
    Pseudoviral neutralization antibody titers were determined against the homologous H1N1 A/New Caledonia/20/99 virus, and were summarized using geometric mean 80% inhibitory concentration (IC80).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

INCLUSION CRITERIA:

  1. Healthy adults between the ages of 18-70 years inclusive
  2. Based on history and examination, in good general health and without history of any of the conditions listed in the exclusion criteria
  3. Received at least one licensed influenza vaccine from 2014 to the present
  4. Able and willing to complete the informed consent process
  5. If enrolled in Group 1: Available for clinic visits for 52 weeks after enrollment and through an influenza season
  6. If enrolled in Group 2A, 2B, 2C, or 2D: Available for clinic visits for 68 weeks after enrollment and through an influenza season
  7. Willing to have blood samples collected, stored indefinitely, and used for research purposes
  8. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
  9. Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) less than or equal to 40 within the 28 days before enrollment

    Laboratory Criteria within 28 days before enrollment

  10. White blood cells (WBC) and differential either within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval
  11. Total lymphocyte count greater than or equal to 800 cells/mm^3
  12. Platelets = 125,000 - 500,000/mm3
  13. Hemoglobin within institutional normal range
  14. Serum iron either within institutional normal range or accompanied by the site PI or designee approval
  15. Serum ferritin within institutional normal range or accompanied by the site PI or designee approval
  16. Alanine aminotransferase (ALT) less than or equal to 1.25 x institutional upper limit of normal (ULN)
  17. Aspartate aminotransferase (AST) less than or equal to 1.25 x institutional ULN
  18. Alkaline phosphatase (ALP) <1.1 x institutional ULN
  19. Total bilirubin within institutional normal range
  20. Serum creatinine less than or equal to 1.1 x institutional ULN
  21. Negative for HIV infection by an FDA-approved method of detection

    Criteria applicable to women of childbearing potential:

  22. Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on the day of enrollment
  23. Agreed to use an effective means of birth control from at least 21 days prior to enrollment through the end of the study

EXCLUSION CRITERIA:

  1. Breast-feeding or planning to become pregnant during the study.

    Participant has received any of the following substances:

  2. More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment
  3. Blood products within 16 weeks prior to enrollment
  4. Live attenuated vaccines within 4 weeks prior to enrollment
  5. Inactivated vaccines within 2 weeks prior to enrollment
  6. Investigational research agents within 4 weeks prior to enrollment or planned to receive investigational products while on the study
  7. Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule
  8. Current anti-TB (tuberculosis) prophylaxis or therapy
  9. Previous investigational H1 influenza vaccine
  10. Previous investigational ferritin-based vaccine
  11. Receipt of a licensed influenza vaccine within 6 weeks before trial enrollment

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

  12. Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the investigator
  13. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
  14. Asthma that is not well controlled
  15. Diabetes mellitus (type I or II), with the exception of gestational diabetes
  16. Thyroid disease that is not well controlled
  17. Idiopathic urticaria within the past year
  18. Autoimmune disease or immunodeficiency
  19. Hypertension that is not well controlled (baseline systolic > 140 mmHg or diastolic > 90 mmHg)
  20. 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
  21. Malignancy that is active or history of malignancy that is likely to recur during the period of the study.
  22. Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years
  23. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
  24. Guillain-Barré Syndrome
  25. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03814720


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Alicia T Widge, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  Study Documents (Full-Text)

Documents provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Additional Information:
Publications:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03814720    
Other Study ID Numbers: 190032
19-I-0032 ( Other Identifier: NIH IRB )
First Posted: January 24, 2019    Key Record Dates
Results First Posted: April 29, 2022
Last Update Posted: April 29, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Flu
Seasonal Allergy
Respiratory Illness
Flu Virus
Viral Infection
Additional relevant MeSH terms:
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Influenza, Human
Infections
Respiratory Tract Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Diseases