Experimental AD4-H5-VTN Vaccine in Healthy Volunteers

NCT01443936 | Completed Phase 1 FDA Drug

• 2 other identifiers: 11025911-I-0259
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

H5N1 Influenza

Keywords

Influenza Vaccine; H5N1 Influenza; Normal Volunteer; Adenovirus; Live Virus Vaccine; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Safety: evaluate local toxicity & systemic reactions to vaccination. Severe reactions to vaccine (i.e. lower respiratory or GI tract disease) or systemic symptoms related to vaccine.

Secondary Outcomes (1)

• Immunogenicity: Data collected for: H5-specific antibody, mucosal humoral, & cellular immune response; vaccine virus shedding & genetic stability; transmission of virus to household/intimate contacts.

Interventions

Ad4-H5-VTN vaccination-tonsillar route BIOLOGICAL

Ad4-H5-vaccination-oral route BIOLOGICAL

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All participants (vaccinees, household contacts, and intimate contacts) must meet all of the following criteria:
• Age 18 to 49 years for vaccinees. Vaccinees may be \>49 years of age at the time of booster vaccination. Age 18 to 65 years for household and intimate contacts.
• Negative FDA-approved HIV test
• Able to provide proof of identity to the acceptance of the Principal Investigator or designee during enrollment.
• Available and willing to participate in follow-up visits and tests for the duration of the study,
• Willing to have samples stored for future research.
• Negative \<=-HCG pregnancy test for females presumed to be of reproductive potential.
• A female 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.
• Participant agrees to be heterosexually inactive or consistently practice contraception at least 21 days
• prior to enrollment and 28 days following vaccination. Acceptable methods of contraception
• include the following:
• condoms, male or female, with a spermicide
• diaphragm or cervical cap with spermicide

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.
• 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.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Amara RR, Villinger F, Altman JD, Lydy SL, O'Neil SP, Staprans SI, Montefiori DC, Xu Y, Herndon JG, Wyatt LS, Candido MA, Kozyr NL, Earl PL, Smith JM, Ma HL, Grimm BD, Hulsey ML, Miller J, McClure HM, McNicholl JM, Moss B, Robinson HL. Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science. 2001 Apr 6;292(5514):69-74. doi: 10.1126/science.1058915.

  PMID: 11393868 BACKGROUND

• Baba TW, Jeong YS, Pennick D, Bronson R, Greene MF, Ruprecht RM. Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques. Science. 1995 Mar 24;267(5205):1820-5. doi: 10.1126/science.7892606.

  PMID: 7892606 BACKGROUND

• Baba TW, Liska V, Khimani AH, Ray NB, Dailey PJ, Penninck D, Bronson R, Greene MF, McClure HM, Martin LN, Ruprecht RM. Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques. Nat Med. 1999 Feb;5(2):194-203. doi: 10.1038/5557.

  PMID: 9930868 BACKGROUND

• Matsuda K, Migueles SA, Huang J, Bolkhovitinov L, Stuccio S, Griesman T, Pullano AA, Kang BH, Ishida E, Zimmerman M, Kashyap N, Martins KM, Stadlbauer D, Pederson J, Patamawenu A, Wright N, Shofner T, Evans S, Liang CJ, Candia J, Biancotto A, Fantoni G, Poole A, Smith J, Alexander J, Gurwith M, Krammer F, Connors M. A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity. J Clin Invest. 2021 Mar 1;131(5):e140794. doi: 10.1172/JCI140794.

  PMID: 33529172 DERIVED

MeSH Terms

Conditions

Influenza, Human; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; DNA Virus Infections

Study Officials

• Mark Connors, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2011
• First Posted: September 30, 2011
• Study Start: September 14, 2011
• Primary Completion: April 24, 2018
• Study Completion: April 24, 2019
• Last Updated: December 16, 2019

Record last verified: 2019-04-24

Locations

US (1)