Dose, Safety, Tolerability and Immunogenicity of an Influenza H10 Stabilized Stem Ferritin Vaccine, VRC-FLUNPF0103-00-VP, in Healthy Adults
Study Details
Study Description
Brief Summary
Background:
Influenza (flu) is a contagious respiratory illness. It is caused by influenza viruses that infect the nose, throat, and lungs. Some people, such as older people, young children, and people with certain health conditions, are at high risk of serious flu complications. Researchers want to test a vaccine to prevent flu.
Objective:
To see if the H10 Ferritin vaccine is safe and how the body responds to it.
Eligibility:
Healthy adults ages 18-70.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood tests
Pregnancy test (if needed).
Participants will get 1-2 injections of the study vaccine in the upper arm. They will stay in the clinic for at least 30 minutes after each vaccination.
Participants will keep a diary card for 7 days after each vaccination. They will record their temperature and any symptoms. They will measure any skin changes at the injection site.
Participants may have nose and throat secretions, and/or oral mucosal samples, collected with a disposable swab.
Participants will have blood drawn.
Some participants may have apheresis. A needle is placed into a vein in both arms. Blood is removed through a needle in the vein of one arm. The blood is spun in a machine that separates the white blood cells. The rest of the blood is returned to the participant through a needle in the other arm. Before apheresis, participants weight, pulse, and blood pressure will be checked. Their medical history will be taken.
Participants will have 8-10 follow-up visits. Participation will last about 10 months.
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| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Design:
This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of VRC-FLUNPF0103-00-VP in 2 regimens. The hypotheses are that the vaccine is safe and tolerable and will elicit an immune response. The primary objective is to evaluate the safety and tolerability of the investigational vaccine in healthy adults. Secondary objectives are related to immunogenicity of the investigational vaccine and dosing regimen.
Study Products:
The investigational vaccine, VRC-FLUNPF0103-00-VP (H10ssF-6473), was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID) and is composed of Helicobacter pylori non-heme ferritin assembled with influenza virus H10 haemagglutinin (HA) insert to form a nanoparticle displaying eight HA stabilized stems trimers from A/Jiangxi/IPB13/2013 (H10N8) influenza. The vaccine is supplied in single-use vials at a concentration of 180 mcg/mL. VRC-PBSPLA043-00-VP consisting of sterile phosphate buffered saline (PBS) will be the diluent for H10ssF-6473. Prepared study product will be administered intramuscularly (IM) in the deltoid muscle via needle and syringe.
Subjects:
Healthy adults between the ages of 18-70 will be enrolled; adults born between 1965 and 1970 will be excluded from the trial.
Study Plan: This study will evaluate the safety, tolerability and immunogenicity of 1 or 2 doses of H10ssF-6473 in a dose-escalation design. In Group 1, the first 3 subjects will receive a single low dose (20 mcg) of H10ssF-6473 on Day 0. If assessed as safe and tolerable two weeks after vaccination of the third subject, enrollment will continue for the additional subjects in Group 1 and begin for Group 2A. For Group 1, the protocol requires 1 vaccination visit, 8 follow-up visits, and a telephone contact after vaccination.
Groups 2A and 2B are stratified by age as shown in the vaccination schema. In Group 2A, the first 3 subjects will receive a higher dose (60 mcg) of H10ssF-6473 on Day 0. If assessed as safe and tolerable two weeks after vaccination of the third subject, enrollment will continue in Group 2A, begin for Group 2B, and subjects may receive the second vaccination at week 16. For Groups 2A and 2B, the protocol requires 2 vaccination visits, 10 follow-up visits, and a telephone contact after each vaccination.
For all groups, solicited reactogenicity will be evaluated using a 7-day diary card. Assessment of vaccine safety will include clinical observation and monitoring of hematological and chemical parameters at clinical visits throughout the study.
VRC 323 Va.ccination Schema:
Group 1, Age Cohort: 18-50, Subjects: 5, Day 0: 20 mcg IM, Week 16: no dose
Group 2A, Age Cohort: 18-50, Subjects: 10-15, Day 0: 60 mcg IM, Week 16: 60 mcg IM
Group 2B, Age Cohort: 55-70, Subjects: 10-15, Day 0: 60 mcg IM, Week 16: 60 mcg IM
Total Subjects: 25-35*
*Enrollment up to 45 is permitted if additional subjects are needed for safety or immunogenicity evaluations.
Study Duration:
Subjects will be evaluated for 40 weeks following the first vaccine administration.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group 1 20 mcg IM at Day 0 |
Biological: VRC-FLUNPF0103-00-VP VRC-FLUNPF0103-00-VP (H10ssF-6473)
The vaccine is composed of the 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.
|
| Experimental: Group 2A 60 mcg IM at Day 0 and Week 16 |
Biological: VRC-FLUNPF0103-00-VP VRC-FLUNPF0103-00-VP (H10ssF-6473)
The vaccine is composed of the 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.
|
| Experimental: Group 2B 60 mcg IM at Day 0 and Week 16 |
Biological: VRC-FLUNPF0103-00-VP VRC-FLUNPF0103-00-VP (H10ssF-6473)
The vaccine is composed of the 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.
|
Outcome Measures
Primary Outcome Measures
- Unsolicited adverse events [Day 0 through 28 days post product administration]
Occurrence of unsolicited non-serious adverse events
- Systemic Reactogenicity [7 days after each product administration]
Occurrence of systemic reactogenicity signs and symptoms
- Serious adverse events [Day 0 through Day 280]
Occurrence of serious adverse events
- New chronic medical conditions [Day 0 through Day 280]
Occurrence of new-onset of chronic medical conditions
- Local Reactogenicity [7 days after each product administration]
Occurrence of local reactogenicity signs and symptoms
- Laboratory measures [Day 0 through 28 days post product administration]
Occurrence of laboratory safety measures
Secondary Outcome Measures
- Group 2A-2B: vaccine-induced antibodies [Day 0 and 2 weeks after each product administration]
Stem-specific antibody responses to H10ssF-6473
- Group 1: vaccine-induced antibodies [Day 0 and 28 days post product administration]
Stem-specific antibody responses to H10ssF-6473
Eligibility Criteria
Criteria
- INCLUSION CRITERIA:
A subject must meet all of the following criteria:
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Healthy adults between the ages of 18-70 years (excluding adults born between January 1, 1965 and December 31,1970)
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Based on history and examination, in good general health and without history of any of the conditions listed in the exclusion criteria
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Received at least one licensed influenza vaccine from 2015 to the present
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Able and willing to complete the informed consent process
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Available for clinic visits for 40 weeks after enrollment
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Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
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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
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White blood cells (WBC) and differential within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval
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Total lymphocyte count greater than or equal to 800 cells/microL
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Platelets = 125,000 - 500,000 cells/microL
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Hemoglobin within institutional normal range or accompanied by the PI or designee approval
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Serum iron within institutional normal range or accompanied by the site PI or designee approval
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Serum ferritin within institutional normal range or accompanied by the site PI or designee approval
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Alanine aminotransferase (ALT) less than or equal to 1.25 x institutional upper limit of normal (ULN)
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Aspartate aminotransferase (AST) less than or equal to 1.25 x institutional ULN
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Alkaline phosphatase (ALP) <1.1 x institutional ULN
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Total bilirubin within institutional normal range, except when otherwise consistent with Gilbert s syndrome
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Serum creatinine less than or equal to 1.1 x institutional ULN
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Negative for HIV infection by an FDA-approved method of detection
Criteria applicable to women of childbearing potential:
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Negative beta-human chorionic gonadotropin (Beta-HCG) pregnancy test (urine or serum) on the day of enrollment
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Agrees to use an effective means of birth control from at least 21 days prior to enrollment through the end of the study
EXCLUSION CRITERIA:
A subject will be excluded if one or more of the following conditions apply:
- Breast-feeding or planning to become pregnant during the study
Subject has received any of the following substances:
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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
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Blood products within 16 weeks prior to enrollment
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Live attenuated vaccines within 4 weeks prior to enrollment
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Inactivated vaccines within 2 weeks prior to enrollment
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Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study
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Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule
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Current anti-TB prophylaxis or therapy
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Previous investigational H10 influenza vaccine
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Receipt of a licensed influenza vaccine within 6 weeks prior to enrollment
Subject has a history of any of the following clinically significant conditions:
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Serious reactions to vaccines that preclude receipt of the study vaccination as determined by the investigator
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Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
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Asthma that is not well controlled
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Diabetes mellitus (type I or II), with the exception of gestational diabetes
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Thyroid disease that is not well controlled
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Idiopathic urticaria within the past year
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Autoimmune disease or immunodeficiency
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Hypertension that is not well controlled (baseline systolic > 140 mmHg or diastolic > 90 mmHg)
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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
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Malignancy that is active or history of malignancy that is likely to recur during the period of the study
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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
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Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
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Guillain-Barre Syndrome
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Previous or current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) documented by PCR test
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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 subject s ability to give informed consent.
INCLUSION OF VULNERABLE SUBJECTS
Children
Children are not eligible to participate in this clinical trial because the investigational vaccine has not been previously evaluated in adults. If the product is assessed as safe and immunogenic, other protocols designed for children may be conducted in the future.
NIH Employees
NIH employees and members of their immediate families may participate in this protocol. We will follow the Guidelines for the Inclusion of Employees in NIH Research Studies and will give each employee a copy of the 'NIH Information Sheet on Employee Research Participation' and a copy of the 'Leave Policy for NIH Employees Participating in NIH Medical Research Studies.'
Neither participation nor refusal to participate will have an effect, either beneficial or adverse, on the participant s employment or work situation. The NIH information sheet regarding NIH employee research participation will be distributed to all potential subjects who are NIH employees. The employee subject s privacy and confidentiality will be preserved in accordance with NIH CC and NIAID policies. For NIH employee subjects, consent will be obtained by an individual who is independent of the employee s team. If the individual obtaining consent is a co-worker to the subject, independent monitoring of the consent process will be included through the Bioethics Consultation Service. Protocol study staff will be trained on obtaining potentially sensitive and private information from co-workers or subordinates.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institutes of Health Clinical Center | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Principal Investigator: Joseph P Casazza, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- 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.
- 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.
- 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.
- 200145
- 20-I-0145