Experimental AD4-H5-VTN Vaccine in Healthy Volunteers

Completed · Phase 1

Conditions studied: H5N1 Influenza

In brief

This is a Phase 1 randomized, single center, dose-escalation study designed to evaluate the safety and immunogenicity of live, replication competent recombinant Adenovirus type 4-H5N1Influenza Vietnam 1194 Hemagglutinin (HA) (Ad4-H5-Vtn). Determining the optimal route and dose for this recombinant platform will greatly accelerate investigations of this vector as an influenza vaccine and an HIV vaccine platform. Intranasal and tonsillar administration of the vaccine will be separately assessed. The oral enteric-coated capsule will also be assessed in 10 outpatients using similar blood sampling for comparison. The Ad4-H5-Vtn orally administered as enteric-coated capsules has already been evaluated in an ascending dose Phase 1 study, in dosages as high as 10(11) viral particles (vp). The primary goal of this study is to evaluate safety of ascending dosages of the Ad4-H5-Vtn vaccine following intranasal and tonsillar administration. A dosage or dosages will be selected to further evaluate the humoral, cellular, and mucosal immune responses against both the vector and the inserted gene. The Ad4-H5-Vtn will be initiated at 10(3) vp. Once safety is established at the initial dose, a second round of testing will begin at the next ten-fold higher dose. The Ad4-H5-Vtn vaccine will be assessed in three participants at each dosage level. The maximum viral dose administered by the tonsillar route will be 10(8) vp. In addition to clinical and laboratory monitoring of safety, the principal assessments will be shedding of the Ad4-H5-Vtn virus in rectal, cervicovaginal, throat, and nasal swabs, and assessment of the antibody (mucosal and systemic) response to the HA and to the Ad4 virus. When safety has been confirmed in all three participants at a given dosage level, the next higher dose group is enrolled. If one grade 3 or greater toxicity (or pre-specified Grade 2 toxicity, see Section 3.4) attributable to the vaccine is observed, the group will be expanded at that dose. If a second attributable grade 3 or greater toxicity (or pre-specified Grade 2 toxicity, see Section 3.4) is observed, the dose will be reduced one level and the group will be expanded. Up to 25 Ad4-seronegative individuals will be enrolled at the maximum tolerated dose to fully evaluate safety and immunogenicity in the protocol. All participants will be followed for 28 days following immunization, and again at 8 and 26 weeks to evaluate any long-term toxicity and persistence of immunity. Tonsillar Participants will receive a booster dose of vaccine \[SK1\]at the 26-week visit and be seen for follow-up visits at Weeks 30 and 34. Household and intimate contacts will also be enrolled and monitored for Adenovirus and HAI antibodies.

Key facts

Study ID: NCT01443936
Run by: National Institute of Allergy and Infectious Diseases (NIAID)
People needed: 96
Starts: 2011-09-14
Expected to finish: 2019-04-24
Last updated by the study team: 2019-12-16

Who can join

Age: 18 and older, up to 49. Sex: any. Healthy volunteers: accepted.

You may not qualify if…

A participant (vaccinees, household contacts, and intimate contacts) will be excluded if they have the following:
Any condition that, in the investigator's judgement, places the subject at undue risk by participating in the study.
The following exclusion criterion applies to vaccinees and intimate contacts, but not to household contacts:
History of any prior disease or therapy which would affect immune or pulmonary function.
Prior malignancy, except curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
History of radiation therapy or cytotoxic/cancer chemotherapy.
History of insulin-dependent diabetes mellitus.
Immunodeficiency or autoimmune disease.
Acute infection or a recent (within 6 months) history of chronic infection suggestive of immunodeficiency.
Taking any medication which may affect immune function, except participants may be taking low doses of nonprescription strength NSAIDS (including e.g. ibuprofen or aspirin) or acetaminophen.
Chronic respiratory disorders including asthma, emphysema, interstitial lung disease, pulmonary hypertension, recurrent pneumonia, or recent or ongoing respiratory tract infection. If a respiratory disorder is transient, defer immunization but do not exclude the participant.
Active Hepatitis B or C infection, as indicated by the presence of Hepatitis B antigen or Hepatitis C virus (i.e. Hepatitis B or C positive serology with the presence of virus antigen or DNA. Ongoing viral
replication will be confirmed by a Hepatitis B antigen or Hepatitis C viral load).
Female of child-bearing potential who is breast-feeding or planning pregnancy during the 28 days following vaccination.
The following exclusion criteria apply only to vaccinees and not to household or intimate contacts:
Any medical, psychiatric, or social condition, or occupational or other responsibility that, in the judgment of the investigator, would interfere with or serve as a contraindication to receipt of live virus vaccine, protocol adherence, or a participant s ability to give informed consent.
Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well controlled on medication for the past two years; disorder requiring lithium; or suicidal ideation occurring within five years prior to enrollment.
Participants that live in the same house or apartment with any of the following will be excluded:
An individual under 18 years of age
An immunocompromised or immunosuppressed individual
An individual with chronic respiratory disease
A woman who is currently pregnant or planning a pregnancy during the period of immunization
Healthcare worker who has direct contact with immunodeficient, unstable patients, or pediatric patients.
Participants caring for children <36 months of age. Potential vaccinees with any household or intimate contact who cares for children <36 months of age will also be excluded.
Receipt of any of the following:

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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