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Safety and Immunogenicity of Ad4-HIV Envelope Vaccine Vectors in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT03878121
Recruitment Status : Recruiting
First Posted : March 18, 2019
Last Update Posted : September 23, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information
First Submitted Date  ICMJE March 15, 2019
First Posted Date  ICMJE March 18, 2019
Last Update Posted Date September 23, 2019
Actual Study Start Date  ICMJE April 17, 2019
Estimated Primary Completion Date April 15, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 2, 2019)
Safety and immunogenicity [ Time Frame: ongoing ]
Laboratory results and Adverse Events
Original Primary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
Safety and immunogenicity [ Time Frame: Timepoints from Day 0 until 12 month EOS visit. ]
Change History Complete list of historical versions of study NCT03878121 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2019)
Boosting, transmission, and stability [ Time Frame: Months 6.5 and 12 ]
Laboratory events, mucosal samples, adverse events
Original Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
Boosting, transmission, and stability [ Time Frame: 6.5 and 12 month visits ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Immunogenicity of Ad4-HIV Envelope Vaccine Vectors in Healthy Volunteers
Official Title  ICMJE Phase I Open-Label Study of Safety and Immunogenicity of AD4-HIV Envelope Vaccine Vectors in Healthy Volunteers
Brief Summary

Background:

Researchers want see if three new HIV (human immunodeficiency virus) vaccines are safe. Two vaccines are carried by live adenoviruses, which are natural and typically cause cold symptoms or an eye infection. Researchers want to see if all the vaccines help fight HIV and if the adenoviruses are contagious.

Objectives:

To test the safety and effects of three new HIV vaccines.

Eligibility:

Healthy adults 18 49 years old (vaccinees)

Their household and intimate contacts 18 65 years old

Design:

Vaccinees will be screened with:

Physical exam

Medical history

Blood and urine tests

Questions about HIV risk

Vaccinees will learn how to prevent spreading the viruses and about required contraception during the study.

Vaccinees will get consent forms for their household and intimate contacts. All contacts must be age 18 65. All intimate contacts must sign a consent form. Contacts will have 4 visits over 8 months for blood tests and a physical exam.

All applicable participants will have a pregnancy test at every visit.

Vaccinees will have about 9 visits over 12 months. They will repeat screening tests and get:

1 of the 2 adenovirus vaccines sprayed in the nose at 2 visits

The booster vaccine by needle in an arm at 1 visit

Nasal swabs taken at some visits

Vaccinees will note their temperature and symptoms for at least 1 4 weeks after each vaccine.

Vaccinees may choose to have:

Leukapheresis. Blood will be removed by needle in a vein in one arm. A machine will remove white blood cells. The rest of the blood will be returned into the other arm.

Small pieces of the tonsil removed

Sponsoring Institute: National Institute of Allergy and Infectious Diseases

Detailed Description

This is a Phase 1 study to evaluate the immunogenicity and safety of adenovirus serotype 4 (Ad4)-based HIV vaccines when administered via the intranasal route to healthy human volunteers. It is hypothesized that the vaccines will be safe for human administration and will elicit immune responses to the HIV components. All study activities will be carried out at the NIH.

Each study vaccinee will receive 5x10^8 viral particles of either Ad4-Env150KN or Ad4-Env145NFL, administered as an intranasal spray at months 0 and 2. An intramuscular protein booster vaccination with the heterologous soluble trimeric protein VRC-HIVRGP096-00-VP (Trimer 4571) with alum will be administered to all vaccinees at month 6. Specimens to evaluate immunogenicity will be taken at baseline and at specified time points through month 12. The HIV-specific immune responses will be assessed by cellular immune function assays (intracellular cytokine analysis, flow cytometry-based killing assays), as well as measures of humoral immunity (enzyme-linked immunosorbent assay [ELISA] and neutralization assays).

The overall goal will be to compare the safety and immunogenicity of the Ad-HIV vaccine regimens. Participants who have previously received another HIV vaccine and/or are Ad4 seropositive will be enrolled into an exploratory arm to be analyzed separately.

Household contacts willing to participate and all intimate contacts (current and/or those expected within the first 4 weeks after vaccination) will also be enrolled and monitored for transmission of the vaccine virus by serology.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Healthy Volunteer
Intervention  ICMJE
  • Biological: Ad4-Env145NFL
    10^8 vp doses of Ad4-Env145NFL formulated as a liquid for intranasal administration.
  • Biological: Ad4-Env150KN
    10^8 vp doses of Ad4-Env150KN formulated as a liquid for intranasal administration.
  • Biological: VRC-HIVRGP096-00-VP (Trimer 4571) with alum
    500-mcg dose of protein boost vaccine formulated for intramuscular administration.
Study Arms  ICMJE
  • Experimental: A1
    Ad4-Env150KN at Day 0 and 2 months followedVRC-HIVRGP096-00-VP at 6 months.
    Interventions:
    • Biological: Ad4-Env150KN
    • Biological: VRC-HIVRGP096-00-VP (Trimer 4571) with alum
  • Experimental: A2
    Ad4-Env145NFL at Day 0 and 2 months followedVRC-HIVRGP096-00-VP at 6 months.
    Interventions:
    • Biological: Ad4-Env145NFL
    • Biological: VRC-HIVRGP096-00-VP (Trimer 4571) with alum
  • Experimental: B1 (exploratory)
    Previously vaccinated; Ad4-Env150KN at Day 0 and 2 months followed VRC-HIVRGP096-00-VP at 6 months.
    Interventions:
    • Biological: Ad4-Env150KN
    • Biological: VRC-HIVRGP096-00-VP (Trimer 4571) with alum
  • Experimental: B2 (exploratory)
    Previously vaccinated; Ad4-Env145NFL at Day 0 and 2 months followed VRC-HIVRGP096-00-VP at 6 months.
    Interventions:
    • Biological: Ad4-Env145NFL
    • Biological: VRC-HIVRGP096-00-VP (Trimer 4571) with alum
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 15, 2019)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 15, 2024
Estimated Primary Completion Date April 15, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:

All participants (vaccinees, household contacts, and intimate contacts) must meet all of the following criteria:

  1. Age 18 to 49 years for vaccinees. Age 18 to 65 years for household and intimate contacts.
  2. Negative FDA-approved HIV test.
  3. Available and willing to participate in follow-up visits and tests for the duration of the study.
  4. Willing to have samples stored for future research.

The following inclusion criteria apply to vaccinees and intimate contacts, but not to household contacts:

  1. In good general health without clinically significant medical history.
  2. Willing to discuss HIV infection risks with the study clinicians, assessed as low risk for HIV infection, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required clinic visit in the protocol schedule.
  3. Negative beta-HCG pregnancy test for females presumed to be of reproductive potential.
  4. Female vaccinees and male intimate contacts must meet one of the following criteria:

    -The female vaccinee has no reproductive potential because of menopause (1 year without menses) or because of a hysterectomy, bilateral oophorectomy, medically-documented ovarian failure, or tubal ligation.

    or

    -The female vaccinee and her male intimate contact(s) agree to be heterosexually inactive or consistently practice contraception at least 21 days prior to each vaccination through 28 days following each vaccination. Acceptable methods of contraception include any of

    the following:

    • condoms, male or female, with a spermicide.
    • diaphragm or cervical cap with spermicide.
    • contraceptive pills, Norplant, or Depo-Provera (and is not on any medications that would interfere with the effectiveness of these contraceptive agents).
    • male partner has previously undergone a vasectomy for which there is documentation.
    • intrauterine device.
  5. Male vaccinees and female intimate contacts must agree to consistently practice abstinence or effective birth control (described above) and for 28 days following each vaccination.

The following inclusion criteria apply only to vaccinees and not to household or intimate contacts:

  1. Willing to receive HIV test results and abide by NIH guidelines for partner notification of positive HIV results.
  2. Physical examination and laboratory results without clinically significant findings within the 8 weeks prior to enrollment.
  3. Willing to avoid other investigational and/or HIV vaccinations, other than the study agent, from screening through the end-of-study visit.
  4. Safety laboratory criteria within 8 weeks prior to enrollment:

    • Hematopoietic:

      • White blood cell count and lymphocyte count within 25% of both the lower limit and upper limit of normal for the NIH CC (ranges: 2.985-12.55 K/uL for white blood cells and 0.885 - 4.675 K/uL for lymphocytes).
      • Platelet count of least 150,000/mm3.
      • Hemoglobin count within 10% of both the lower limit and upper limit of normal for the NIH CC (ranges: Females 10.08 - 17.27 g/dL, Males 12.33 -19.25 g/dL)
    • Renal: Blood urea nitrogen (BUN) <23 mg/dL; creatinine within normal limits for the NIH CC (females: 0.51-0.95 mg/dL; males: 0.67-1.17 mg/dL).
    • Hepatic: Serum direct bilirubin within normal limits for the NIH CC (0.0 to 0.3 mg/dL).
    • Metabolic: Alanine aminotransferase (ALT) < 2 times upper limit of normal range (females: <66 U/L; males: <82 U/L).
    • Endocrine: Serum glucose within normal range.
  5. Additional laboratory criteria:

    • Immunologic: No history of hypogammaglobulinemia.
    • Serologic: Ad4 neutralizing antibody 80% inhibitory dilution <1:100. (This criterion does not apply to participants in Arm B.)
  6. Willing to follow precautions for preventing the spread of adenovirus in the community.
  7. Males must agree not to donate sperm for 28 days following each study vaccination.

EXCLUSION CRITERIA:

A participant (vaccinees, household contacts, and intimate contacts) will be excluded if they have the following:

1. Any condition that, in the investigator s judgement, places the subject at undue risk by participating in the study.

The following exclusion criteria apply to vaccinees and intimate contacts, but not to household contacts:

  1. History of any prior disease or therapy which would affect immune or pulmonary function.
  2. Prior malignancy, except curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  3. History of radiation therapy or cytotoxic/cancer chemotherapy.
  4. History of diabetes mellitus.
  5. Immunodeficiency or autoimmune disease.
  6. Acute infection or a recent history (within 6 months) of chronic infection suggestive of immunodeficiency.
  7. Taking any glucocorticoids or other immunosuppressive medications.
  8. 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, the study vaccination may be deferred without excluding the participant.
  9. Female of childbearing potential who is breast-feeding or planning pregnancy during the period from enrollment through 28 days following the last study vaccination.

The following exclusion criteria apply only to vaccinees and not to household or intimate contacts:

  1. 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.
  2. 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.
  3. Individuals that live in the same house or apartment with any of the following will be excluded:

    1. An individual under 18 years of age.
    2. An elderly individual (>65 years of age).
    3. An immunocompromised or immunosuppressed individual.
    4. An individual with chronic respiratory disease.
    5. A woman who is currently pregnant or breastfeeding or planning a pregnancy during the period of vaccination.
  4. Healthcare worker who has direct contact with immunodeficient, unstable, elderly, or pediatric patients.
  5. Individuals caring for children <18 years of age or elderly individuals.
  6. Receipt of any of the following:

    • Antiviral medications within 30 days prior to vaccination.
    • Blood products within 120 days prior to HIV screening.
    • Immunoglobulin within 60 days prior to HIV screening.
    • Investigational research drugs or any other investigational agent that in the judgement of the Principal Investigator might interact with the study vaccine within 30 days prior to initial study vaccine administration.
    • Allergy treatment with antigen injections within 30 days of study vaccine administration.
  7. Active hepatitis B or C infection (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 test

    or hepatitis C viral load.

  8. History of Guillain-Barr(SqrRoot)(Copyright) syndrome.
  9. Indeterminate HIV Western blot test.
  10. Prior receipt of the Merck Ad5-based HIV vaccine.
  11. Refusal of any of the individual s intimate contacts to enroll as such on this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: April Poole, R.N. (301) 761-6644 pooleal@mail.nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03878121
Other Study ID Numbers  ICMJE 190069
19-I-0069
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mark Connors, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date September 16, 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP