Influenza A Virus, H5N1 SubtypePhase 1NCT00489931
Phase I Open-Label Study of Recombinant DNA Plasmid Vaccine, VRC-AVIDNA036-00-VP, Encoding for Influenza Virus H5 Hemagglutinin Protein Given Intradermally
A Phase 1 study testing VRC-AVIDNA036-00-VP in people with Influenza A Virus, H5N1 Subtype and Influenza A Virus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will evaluate the safety and effectiveness of a vaccine to prevent avian influenza (bird flu). About 25 to 50 million cases of influenza occur a year in the U.S., leading to 150,000 hospitalizations and 30,000 to 40,000 deaths. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Influenza A Virus, H5N1 Subtype, Influenza A Virus, Influenzavirus A
- What is being tested?
- VRC-AVIDNA036-00-VP
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jun 2007to 15 Apr 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- A participant must meet all of the following criteria:
- 18 to 60 years old.
- Available for clinical follow-up through Week 32.
- Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
- Complete an AoU prior to enrollment and verbalize understanding of all questions answered incorrectly.
- Able and willing to complete the informed consent process.
Show all 30Show fewer
- Willing to donate blood for sample storage to be used for future research.
- In good general health without clinically significant medical history.
- Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) less than 40 within the 28 days prior to enrollment.
- Laboratory Criteria within 28 days prior to enrollment:
- Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.5 g/dL for men
- White blood cells (WBC) = 3,300-12,000 cells/mm(3)
- Differential either within institutional normal range or accompanied by site physician approval
- Total lymphocyte count greater than or equal to 800 cells/mm(3)
- Platelets = 125,000 - 500,000/mm(3)
- Alanine aminotransferase (ALT) less than or equal to 1.25 upper limit of normal
- Serum creatinine less than or equal to 1 times upper limit of normal (less than or equal to 1.3 mg/dL for females; less than or equal to 1.4 mg/dL for males)
- Normal urinalysis, defined as negative glucose, negative or trace protein and no clinically significant blood in the urine.
- Negative FDA-approved HIV blood test. [Note: Results of HIV enzyme-linked immunosorbent assay (ELISA) will be documented, but a negative HIV polymerase chain reaction (PCR) test result will be sufficient for eligibility screening of subjects with positive HIV ELISA that is due to prior participation in an HIV vaccine study]
- Negative hepatitis B surface antigen (HBsAg)
- Negative anti-hepatitis C virus (HCV) antibody and negative HCV PCR.
- Negative for active elicit drug abuse for amphetamines, barbiturates, cocaine, lysergic acid diethylamine (LSD), opiates, or phencyclidine, based on history and urine drug screen performed at the NIH Clinical Center.
- Female-Specific Criteria:
- Negative beta-HCG pregnancy test (urine or serum) for women presumed to be of reproductive potential (i.e., women who have had surgical hysterectomy will not require pregnancy testing).
- A female participant must meet one of the following criteria:
- No reproductive potential because of menopause [one year without menses] or because of a hysterectomy, bilateral oophorectomy, or tubal ligation,
- OR
- Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and through Week 26 of the study,
- OR
- Participant agrees to consistently practice contraception at least 21 days prior to enrollment and through Week 26 of the study by one of the following methods: condoms, male or female, with or without a spermicide; diaphragm or cervical cap with spermicide; intrauterine device; contraceptive pills, patch, implant or any other FDA-approved contraceptive method; male partner has previously undergone a vasectomy.
Who cannot join
- A volunteer will be excluded if one or more of the following conditions apply.
- Women Specific:
- Breast-feeding or planning to become pregnant during the study.
- Volunteer has received any of the following substances:
- Immunosuppressive medications, cytotoxic medications, inhaled corticosteroids, or long-acting beta-agonists within the past three months.
- [Note: The following will NOT exclude study participation:
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- use of corticosteroid nasal spray for rhinitis
- topical corticosteroids for an acute uncomplicated dermatitis
- short-acting beta-agonists in controlled asthmatics
- a short course (10 days or less) of corticosteroids for a non-chronic condition completed at least 2 weeks prior to enrollment in this study]
- Blood products within 120 days prior to HIV screening
- Immunoglobulin within 60 days prior to HIV screening
- Live attenuated vaccines within 30 days prior to initial study vaccine administration
- Investigational research agents within 30 days prior to initial study vaccine administration
- Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 14 days of study vaccine administration
- Current anti-TB prophylaxis or therapy
- Previous H5 avian influenza investigational vaccine.
- Volunteer has a history of any of the following clinically significant conditions:
- Autoimmune disease or immunodeficiency.
- Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain.
- A history of hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema.
- Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that requires the use of oral or intravenous corticosteroids.
- Diabetes mellitus (type I or II), with the exception of gestational diabetes.
- History of thyroidectomy or thyroid disease that required medication within the past 12 months.
- Idiopathic urticaria within the past 2 years
- Hypertension that is not well controlled by medication or is more than 145/95 at enrollment.
- Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with injections or blood draws.
- Malignancy that is active or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of the study.
- Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not requiring treatment within the last 3 years.
- Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen.
- Allergic reaction to aminoglycoside antibiotics.
- Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder; disorder requiring lithium; or within five years prior to enrollment, a history of suicide plan or attempt.
- 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 volunteer's ability to give informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Open-Label Study of the Safety and Immunogenicity of a Recombinant DNA Plasmid Vaccine, VRC-AVIDNA036-00-VP, Encoding for the Influenza Virus H5 Hemagglutinin Protein Administered Intradermally in Healthy Adults
This study will evaluate the safety and effectiveness of a vaccine to prevent avian influenza (bird flu). About 25 to 50 million cases of influenza occur a year in the U.S., leading to 150,000 hospitalizations and 30,000 to 40,000 deaths. Globally, a pandemic influenza may be 1 billion flu cases, with 3 to 5 million cases of severe illness and up to half a million deaths annually. There is potential threat of a pandemic from emerging virus strains for which the population has little or no preexisting immunity. Avian influenza A (H5N1) viruses causing serious disease have emerged recently, affecting domestic and wild bird populations.
Patients ages 18 to 60 who are in good health and not pregnant or breast feeding may be eligible for this study. The study will be done at the NIH Clinical Center by staff of the Vaccine Research Center. It will last about 32 weeks for each person. A traditional needle or a needle-free device called Biojector 2000 will be used. Intramuscular (in the muscle) and subcutaneous (in fat below the skin) delivery of vaccine via Biojector is cleared for use by the Food and Drug Administration and is not considered investigational. Intradermal (in the skin) delivery of vaccine by Biojector in this study is deemed investigational but has been evaluated in humans before, and found safe and well tolerated in other trials.
There will be about 10 clinic visits in this study, and it is important to stay on schedule. Visits are about 2 hours, though on injection days, visits are about 4 hours. Injections are given on day 0 and at weeks 4 and 8. The vaccine is given by injections in the skin on the upper arms. Clinic staff will observe patients for 30 minutes after each vaccination. One to 2 days after the first injection, there will be a clinic visit. One to 3 days after the second and third injections, patients need to telephone clinic staff to report on how they are doing. Patients will complete a diary card at home, recording temperature and symptoms, and looking at the injection site daily for 5 days. Patients should report any side effects to one of the study physicians or nurses as soon as possible. They will return to the clinic 2 weeks after each injection. A needle-free system uses the pressure of carbon dioxide, instead of a needle, to inject the vaccine into the skin. Discomfort can result from either the needle-free device or the needle. There may be stinging, pain, soreness, swelling, bruising, or a small cut in the skin.
Read the detailed description
Study Design: This is a Phase I study to evaluate safety, tolerability, and immunogenicity of a recombinant DNA vaccine against the influenza virus H5 hemagglutinin by intradermal (ID) delivery. The hypothesis is that this vaccine will be safe for human administration by ID delivery by either needle/syringe or Biojector and will elicit antibody and T cell responses against the H5 protein. Primary objectives are to evaluate safety and tolerability of the vaccine at 500 micrograms ID administered by needle and syringe or by Biojector and at 1 mg ID administered by Biojector as two injections in the same or in different arms in healthy adults. Secondary and exploratory objectives are related to immunogenicity.
Product Description: The vaccine is composed of a single closed-circular DNA plasmid that encodes the H5 protein with a CMV/R promoter. Vaccine vials will be supplied at 4 mg/mL. Each injection will be 125 microliters (500 micrograms) administered ID over the deltoid muscle using the Biojector® (Registered Trademark) 2000 Needle-Free Injection Management System (Biojector) or needle and syringe.
Subjects: A total of 40 healthy adults, ages 18-60 years will be enrolled.
Study Plan: Subjects will be simultaneously randomized at a ratio of 1:1:1:1 into one of four groups as shown in the schema. The protocol requires ten clinic visits and three telephone follow-up contacts.
Study Duration: Each participant will complete 32 weeks of clinical follow up.
Study Endpoints: The primary endpoint is safety and tolerability of the regimen. The secondary immunogenicity endpoint is H5-specific antibody as measured by hemagglutination inhibition (HAI) assay and H5 neutralizing antibody assay at Study Week 12. Other immunogenicity assays at timepoints throughout the study may also be completed as exploratory evaluations.
- Conditions
- Influenza A Virus, H5N1 Subtype, Influenza A Virus, Influenzavirus A, Orthomyxovirdae, H5N1 Virus
- Being tested
- VRC-AVIDNA036-00-VP
- Keywords
- Avian Influenza, Healthy, Immunity, Preventive, Bird Flu, Healthy Volunteer, HV
- Medical subject headings
- Influenza in Birds
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VRC-AVIDNA036-00-VPDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (local and systemic reactogenicity, lab tests, AEs)
Secondary outcomes (1)
Immunogenicity (cellular and humoral immune function assays)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2007 (estimated)
- Study start18 Jun 2007
- Study completion15 Apr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Influenza A Virus, H5N1 SubtypeStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00489931
- Sponsor's protocol ID
- 070172
- Other IDs
- 07-I-0172
- Status last verified
- 15 Apr 2009
- First submitted
- 20 Jun 2007
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Subbarao K, Murphy BR, Fauci AS. Development of effective vaccines against pandemic influenza. Immunity. 2006 Jan;24(1):5-9. doi: 10.1016/j.immuni.2005.12.005.
PubMed 16413916Luke CJ, Subbarao K. Vaccines for pandemic influenza. Emerg Infect Dis. 2006 Jan;12(1):66-72. doi: 10.3201/eid1201.051147.
PubMed 16494720Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature. 2005 Oct 6;437(7060):889-93. doi: 10.1038/nature04230.
PubMed 16208372
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-Label Study of the Safety and Immunogenicity of a Recombinant DNA Plasmid Vaccine, VRC-AVIDNA036-00-VP, Encoding for the Influenza Virus H5 Hemagglutinin Protein Administered Intradermally in Healthy Adults
- ClinicalTrials.gov ID
- NCT00489931
- Acronym / sponsor ID
- 070172
- Conditions
- Influenza A Virus, H5N1 Subtype, Influenza A Virus, Influenzavirus A, Orthomyxovirdae, H5N1 Virus
- Keywords
- Avian Influenza, Healthy, Immunity, Preventive, Bird Flu, Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 18 Jun 2007
- Study completion
- 15 Apr 2009
- First posted
- 21 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and effectiveness of a vaccine to prevent avian influenza (bird flu). About 25 to 50 million cases of influenza occur a year in the U.S., leading to 150,000 hospitalizations and 30,000 to 40,000 deaths. Globally, a pandemic influenza may be 1 billion flu cases, with 3 to 5 million cases of severe illness and up to half a million deaths annually. There is potential threat of a pandemic from emerging virus strains for which the population has little or no preexisting immunity. Avian influenza A (H5N1) viruses causing serious disease have emerged recently, affecting domestic and wild bird populations.
Patients ages 18 to 60 who are in good health and not pregnant or breast feeding may be eligible for this study. The study will be done at the NIH Clinical Center by staff of the Vaccine Research Center. It will last about 32 weeks for each person. A traditional needle or a needle-free device called Biojector 2000 will be used. Intramuscular (in the muscle) and subcutaneous (in fat below the skin) delivery of vaccine via Biojector is cleared for use by the Food and Drug Administration and is not considered investigational. Intradermal (in the skin) delivery of vaccine by Biojector in this study is deemed investigational but has been evaluated in humans before, and found safe and well tolerated in other trials.
There will be about 10 clinic visits in this study, and it is important to stay on schedule. Visits are about 2 hours, though on injection days, visits are about 4 hours. Injections are given on day 0 and at weeks 4 and 8. The vaccine is given by injections in the skin on the upper arms. Clinic staff will observe patients for 30 minutes after each vaccination. One to 2 days after the first injection, there will be a clinic visit. One to 3 days after the second and third injections, patients need to telephone clinic staff to report on how they are doing. Patients will complete a diary card at home, recording temperature and symptoms, and looking at the injection site daily for 5 days. Patients should report any side effects to one of the study physicians or nurses as soon as possible. They will return to the clinic 2 weeks after each injection. A needle-free system uses the pressure of carbon dioxide, instead of a needle, to inject the vaccine into the skin. Discomfort can result from either the needle-free device or the needle. There may be stinging, pain, soreness, swelling, bruising, or a small cut in the skin.
Detailed description
Study Design: This is a Phase I study to evaluate safety, tolerability, and immunogenicity of a recombinant DNA vaccine against the influenza virus H5 hemagglutinin by intradermal (ID) delivery. The hypothesis is that this vaccine will be safe for human administration by ID delivery by either needle/syringe or Biojector and will elicit antibody and T cell responses against the H5 protein. Primary objectives are to evaluate safety and tolerability of the vaccine at 500 micrograms ID administered by needle and syringe or by Biojector and at 1 mg ID administered by Biojector as two injections in the same or in different arms in healthy adults. Secondary and exploratory objectives are related to immunogenicity.
Product Description: The vaccine is composed of a single closed-circular DNA plasmid that encodes the H5 protein with a CMV/R promoter. Vaccine vials will be supplied at 4 mg/mL. Each injection will be 125 microliters (500 micrograms) administered ID over the deltoid muscle using the Biojector® (Registered Trademark) 2000 Needle-Free Injection Management System (Biojector) or needle and syringe.
Subjects: A total of 40 healthy adults, ages 18-60 years will be enrolled.
Study Plan: Subjects will be simultaneously randomized at a ratio of 1:1:1:1 into one of four groups as shown in the schema. The protocol requires ten clinic visits and three telephone follow-up contacts.
Study Duration: Each participant will complete 32 weeks of clinical follow up.
Study Endpoints: The primary endpoint is safety and tolerability of the regimen. The secondary immunogenicity endpoint is H5-specific antibody as measured by hemagglutination inhibition (HAI) assay and H5 neutralizing antibody assay at Study Week 12. Other immunogenicity assays at timepoints throughout the study may also be completed as exploratory evaluations.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (30 listed)
- 18 to 60 years old.
- Available for clinical follow-up through Week 32.
- Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
- Complete an AoU prior to enrollment and verbalize understanding of all questions answered incorrectly.
- Able and willing to complete the informed consent process.
Key exclusion criteria (33 listed)
- A volunteer will be excluded if one or more of the following conditions apply.
- Breast-feeding or planning to become pregnant during the study.
- Immunosuppressive medications, cytotoxic medications, inhaled corticosteroids, or long-acting beta-agonists within the past three months.
- use of corticosteroid nasal spray for rhinitis
- topical corticosteroids for an acute uncomplicated dermatitis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VRC-AVIDNA036-00-VP | Drug | – |
Primary outcome
Safety (local and systemic reactogenicity, lab tests, AEs)
1 secondary outcome
Immunogenicity (cellular and humoral immune function assays)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 16413916Subbarao K, Murphy BR, Fauci AS. Development of effective vaccines against pandemic influenza. Immunity. 2006 Jan;24(1):5-9. doi: 10.1016/j.immuni.2005.12.005.
- Background: PubMed 16494720Luke CJ, Subbarao K. Vaccines for pandemic influenza. Emerg Infect Dis. 2006 Jan;12(1):66-72. doi: 10.3201/eid1201.051147.
- Background: PubMed 16208372Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature. 2005 Oct 6;437(7060):889-93. doi: 10.1038/nature04230.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VRC-AVIDNA036-00-VP in people with Influenza A Virus, H5N1 Subtype and Influenza A Virus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (local and systemic reactogenicity, lab tests, AEs). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00489931, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.