An Open-Label, Randomized Phase I Study in Healthy Adults of the Safety and Immunogenicity of Prime-Boost Intervals With Monovalent Influenza Subunit Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc.) Administered Alone or Following Re...
|First Received Date ICMJE||March 12, 2010|
|Last Updated Date||December 14, 2011|
|Start Date ICMJE||February 2010|
|Primary Completion Date||December 2011 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Safety: adverse events, including clinical, laboratory and local and systemic reactogenicity|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01086657 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Immunogenicity as measured by humoral and cellular assays.|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||An Open-Label, Randomized Phase I Study in Healthy Adults of the Safety and Immunogenicity of Prime-Boost Intervals With Monovalent Influenza Subunit Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc.) Administered Alone or Following Re...|
|Official Title ICMJE||VRC 310: An Open-Label, Randomized Ph I: Healthy Adults of Prime-Boost Intervals w/Monovalent Influenza Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc), Administered Alone or Following Recombinant H5 DNA Vaccine|
- New vaccines against avian influenza, also known as "bird flu," are being developed and require testing to determine if they are safe and effective and whether they have any side effects. Researchers are interested in testing two experimental avian influenza vaccines to see whether they are safe, if there are any side effects from the vaccines, and how the body's immune response differs in response to different vaccination schedules. One vaccine is an inactivated vaccine (made with killed or weakened influenza) and one is a DNA vaccine that allows the body to use vaccine to make an immune system response to a specific part of an avian influenza protein.
- Healthy individuals between 18 and 60 years of age.
An Open-Label, Randomized Phase I Study in Healthy Adults of the Safety and Immunogenicity of Prime-Boost Intervals with Monovalent Influenza Subunit Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc), Administered Alone or Following Recombinant DNA Plasmid (H5) Vaccine, VRC-AVIDNA036-00-VP (VRC, NIAID)
This is a Phase I, randomized, open-label study to evaluate the safety, tolerability, and immunogenicity of prime-boost vaccination regimens against the influenza virus hemagglutinin H5. One group will receive A/Indonesia/05/2005 (inactivated H5N1) vaccine as both prime and boost, and the other groups will receive the VRC-AVIDNA036-00-VP (DNA) vaccine as prime with inactivated H5N1 boost but with various boost intervals. The VRC 310 study will provide data from different prime-boost schedules to identify whether homologous or heterologous schedules result in a better antibody response as well as which interval of time between vaccinations is associated with the best immune response. The hypothesis is that all of the study regimens will be safe for human administration and will elicit antibody and T cell responses against the H5 protein. The primary objectives are to evaluate the safety and tolerability of the investigational vaccine regimens, at a dose of 4 mg for the DNA vaccine and 90 microg for the inactivated H5N1, in healthy adults. Secondary and exploratory objectives are related to the immunogenicity of the study vaccine regimens and identification of an interval between prime and boost that has the highest frequency of strong immune responses.
The inactivated H5N1 vaccine is monovalent subunit virion vaccine, A/Indonesia/05/2005 clade 2, manufactured by Sanofi Pasteur, Inc (Swiftwater, PA). Vaccine vials will be supplied at 90 microg/0.5mL. The VRC-AVIDNA036-00-VP vaccine was developed and manufactured by VRC, NIAID and 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 vaccination will be administered intramuscularly (IM) in the deltoid muscle using needle and syringe for the H5N1 vaccine and the Biojector 2000 Needle-Free Injection Management System (Biojector) for the DNA vaccine.
A total of 60 healthy adults, ages 18-60 years will be enrolled.
Subjects will be simultaneously randomized equally into one of 6 groups. Subjects and clinicians will be blinded to group assignment until Day 0 following completion of the enrollment. At the point of enrollment the randomly assigned regimen will become known to subjects and clinicians. Subjects will receive two injections on the schedule shown in the schema. The protocol requires 5 or 6 clinic visits, depending upon the group, and telephone follow-up contact after the first study injection and 24 weeks after the second study injection. Additional optional visits may be conducted at study weeks 48 and 72 to collect blood for evaluation of immune response durability.
Each participant will complete clinical follow up through 24 weeks after the second vaccination. Duration of the expected time on study will vary from 28 to 48 weeks depending upon the Group, but may be extended to 72 weeks after enrollment for subjects who agree to complete the optional research blood drawas.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Condition ICMJE||Influenza A Virus, H5N1 Subtype|
|Study Arm (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||December 2011|
|Primary Completion Date||December 2011 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
A subject must meet all of the following criteria:
18 to 60 years old.
Available for clinical follow-up for up to 32 weeks after enrollment.
Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
Complete an Assessment of Understanding (AoU) questionnaire prior to enrollment and verbalize understanding of all questions answered incorrectly.
Able and willing to complete the informed consent process.
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) < 40 within the 56 days prior to enrollment.
Laboratory Criteria within 56 days prior to enrollment:
Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to13.5 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/mm3
Platelets = 125,000 - 500,000/mm(3)
Alanine aminotransferase (ALT) < 1.25 x upper limit of normal (ULN)
Serum creatinine less than or equal to 1 x ULN (less than or equal to1.3 mg/dL for females; less than or equal to1.4 mg/dL for males)
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 beta-HCG pregnancy test (urine or serum) for women presumed to be of reproductive potential.
A female subject 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,
Agrees to be heterosexually inactive at least 21 days prior to enrollment and through8 weeks after last injection,
Agrees to consistently practice contraception at least 21 days prior to enrollment and through 8 weeks after last injection by one of the following methods:
A subject will be excluded if one or more of the following conditions apply.
Breast-feeding or planning to become pregnant during the first 28 weeks after enrollment in the study.
Subject has received any of the following substances:
Systemic immunosuppressive medications or cytotoxic medications within the 12 weeks prior to enrollment. [With the exception that a short course (duration of 10 days or less or a single injection) of corticosteroids for a self-limited condition at least 2 weeks prior to enrollment in this study will not exclude study participation.]
Blood products within 112 days (16 weeks) prior to HIV screening
Immunoglobulin within 56 days (8 weeks) prior to HIV screening
Live attenuated vaccines within 28 days (4 weeks) prior to initial study vaccine administration
Investigational research agents within 28 days (4 weeks) 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 (2 weeks) of initial study vaccine administration
Current anti-TB prophylaxis or therapy
Previous H5 avian influenza investigational vaccine.
Subject has a history of any of the following clinically significant conditions:
Contraindication to receiving an FDA approved current seasonal influenza vaccination (e.g., egg allergy)
Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the investigator.
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.
Thyroid disease that is not well controlled.
Idiopathic urticaria within the past year
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 IM 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, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required 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 5 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.
|Ages||18 Years to 60 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01086657|
|Other Study ID Numbers ICMJE||100069, 10-I-0069|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||December 2011|
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