Evaluating the Safety and Immunogenicity of an HIV Vaccine (gp145 C.6980) in Healthy, HIV-Uninfected Adults in the United States
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: gp145 C.6980 Vaccine; Placebo; Aluminum Hydroxide Adjuvant
Intervention description: Administered by intramuscular injection in the deltoid.; Sodium Chloride for Injection, 0.9%; Administered by intramuscular injection in the deltoid.; Administered by intramuscular injection in the deltoid.
Intervention MeSH terms: Aluminum Hydroxide
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of an
      HIV vaccine (gp145 C.6980) with aluminum hydroxide adjuvant in healthy, HIV-1-uninfected
      adults in the United States.
    

Eligibility criteria:

        Inclusion Criteria:

        General and Demographic Criteria

          -  Age of 18 to 50 years

          -  Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site
             (CRS) and willingness to be followed for the planned duration of the study

          -  Ability and willingness to provide informed consent

          -  Assessment of understanding: volunteer demonstrates understanding of this study and
             completes a questionnaire prior to first vaccination with verbal demonstration of
             understanding of all questionnaire items initially answered incorrectly

          -  Agrees not to enroll in another study of an investigational research agent before the
             last scheduled protocol clinic visit

          -  Good general health as shown by medical history, physical exam, and screening
             laboratory tests

        HIV-Related Criteria:

          -  Willingness to receive HIV test results

          -  Willingness to discuss HIV infection risks and amenable to HIV risk reduction
             counseling.

          -  Assessed by the clinic staff as being at "low risk" for HIV infection and committed to
             maintaining behavior consistent with low risk of HIV exposure through the last
             required protocol clinic visit. Low risk guidelines are found on the protocol web page
             under Study Materials on the HVTN Members' site
             (https://members.hvtn.org/protocols/hvtn122).

        Laboratory Inclusion Values

        Hemogram/Complete Blood Count (CBC)

          -  Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female,
             greater than or equal to 13.0 g/dL for volunteers who were born male

          -  White blood cell count equal to 3,300 to 12,000 cells/mm^3

          -  Total lymphocyte count greater than or equal to 800 cells/mm^3

          -  Remaining differential either within institutional normal range or with site physician
             approval

          -  Platelets equal to 125,000 to 550,000/mm^3

        Chemistry

          -  Chemistry panel: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
             alkaline phosphatase less than 1.25 times the institutional upper limit of normal;
             creatinine less than or equal to institutional upper limit of normal.

        Virology

          -  Negative HIV-1 and -2 blood test: US volunteers must have a negative US Food and Drug
             Administration (FDA)-approved enzyme immunoassay (EIA).

          -  Negative Hepatitis B surface antigen (HBsAg)

          -  Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase
             chain reaction (PCR) if the anti-HCV is positive

        Urine:

          -  Normal urine:

               -  Negative urine glucose, and

               -  Negative or trace urine protein, and

               -  Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a
                  microscopic urinalysis with red blood cells levels within institutional normal
                  range).

        Reproductive Status:

          -  Volunteers who were born female: negative serum or urine beta human chorionic
             gonadotropin pregnancy test performed prior to vaccination on the day of initial
             vaccination. Persons who are NOT of reproductive potential due to having undergone
             total hysterectomy or bilateral oophorectomy (verified by medical records), are not
             required to undergo pregnancy testing.

          -  Reproductive status: A volunteer who was born female must:

               -  Agree to consistently use effective contraception (see the protocol for more
                  information) for sexual activity that could lead to pregnancy from at least 21
                  days prior to enrollment until after the last required protocol clinic visit.
                  Effective contraception is defined as using the following methods:

               -  Condoms (male or female) with or without a spermicide,

               -  Diaphragm or cervical cap with spermicide,

               -  Intrauterine device (IUD),

               -  Hormonal contraception, or

               -  Any other contraceptive method approved by the HVTN 122 Protocol Safety Review
                  Team (PSRT),

               -  Successful vasectomy in the male partner (considered successful if a volunteer
                  reports that a male partner has [1] documentation of azoospermia by microscopy,
                  or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite
                  sexual activity postvasectomy);

               -  Or not be of reproductive potential, such as having reached menopause (no menses
                  for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal
                  ligation;

               -  Or be sexually abstinent.

          -  Volunteers who were born female must also agree not to seek pregnancy through
             alternative methods, such as artificial insemination or in vitro fertilization until
             after the last required protocol clinic visit

        Exclusion Criteria:

        General

          -  Blood products received within 120 days before first vaccination

          -  Investigational research agents received within 30 days before first vaccination

          -  Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35
             with 2 or more of the following: age greater than 45, systolic blood pressure greater
             than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, known
             hyperlipidemia

          -  Intent to participate in another study of an investigational research agent or any
             other study that requires non-HVTN HIV antibody testing during the planned duration of
             the HVTN 122 study

          -  Pregnant or breastfeeding

          -  Active duty and reserve US military personnel

        Vaccines and other Injections

          -  HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received
             control/placebo in an HIV vaccine trial, the HVTN 122 PSRT will determine eligibility
             on a case-by-case basis.

          -  Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine
             trial. Exceptions may be made by the HVTN 122 PSRT for vaccines that have subsequently
             undergone licensure by the FDA. For volunteers who have received control/placebo in an
             experimental vaccine trial, the HVTN 122 PSRT will determine eligibility on a
             case-by-case basis. For volunteers who have received an experimental vaccine(s)
             greater than 5 years ago, eligibility for enrollment will be determined by the HVTN
             122 PSRT on a case-by-case basis.

          -  Live attenuated vaccines other than influenza vaccine received within 30 days before
             or scheduled and intended to be received within 14 days after the first vaccination
             (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow
             fever)

          -  Influenza vaccine or any vaccines that are not live attenuated vaccines and were
             received within 14 days prior to first vaccination (eg, tetanus, pneumococcal,
             Hepatitis A or B)

          -  Allergy treatment with antigen injections within 30 days before first vaccination or
             that are scheduled and intended to be received within 14 days after first vaccination

        Immune System

          -  Immunosuppressive medications received within 168 days before first vaccination. (Not
             exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical
             corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of
             prednisone or equivalent at doses less than 60 mg/day and length of therapy less than
             11 days with completion at least 30 days prior to enrollment.)

          -  Serious adverse reactions to vaccines or to vaccine components, including history of
             anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema,
             and/or abdominal pain. (Not excluded from participation: a volunteer who had a
             nonanaphylactic adverse reaction to pertussis vaccine as a child.)

          -  Immunoglobulin received within 60 days before first vaccination

          -  Autoimmune disease

          -  Immunodeficiency

        Clinically significant medical conditions

          -  Untreated or incompletely treated syphilis infection

          -  Clinically significant medical condition, physical examination findings, clinically
             significant abnormal laboratory results, or past medical history with clinically
             significant implications for current health. A clinically significant condition or
             process includes but is not limited to:

               -  A process that would affect the immune response,

               -  A process that would require medication that affects the immune response,

               -  Any contraindication to repeated injections or blood draws,

               -  A condition that requires active medical intervention or monitoring to avert
                  grave danger to the volunteer's health or well-being during the study period,

               -  A condition or process for which signs or symptoms could be confused with
                  reactions to vaccine, or

               -  Any condition specifically listed among the exclusion criteria below.

          -  Any medical, psychiatric, occupational, or other condition that, in the judgment of
             the investigator, would interfere with, or serve as a contraindication to, protocol
             adherence, assessment of safety or reactogenicity, or a volunteer's ability to give
             informed consent

          -  Psychiatric condition that precludes compliance with the protocol. Specifically
             excluded are persons with psychoses within the past 3 years, ongoing risk for suicide,
             or history of suicide attempt or gesture within the past 3 years.

          -  Current anti-tuberculosis (TB) prophylaxis or therapy

          -  Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as
             defined in the most recent National Asthma Education and Prevention Program (NAEPP)
             Expert Panel report). Exclude a volunteer who:

               -  Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or

               -  Uses moderate/high dose inhaled corticosteroids, or

               -  In the past year has either of the following:

               -  Greater than 1 exacerbation of symptoms treated with oral/parenteral
                  corticosteroids;

               -  Needed emergency care, urgent care, hospitalization, or intubation for asthma.

          -  Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not
             excluded: history of isolated gestational diabetes.)

          -  Thyroidectomy, or thyroid disease requiring medication during the last 12 months

          -  Hypertension:

               -  If a person has been found to have elevated blood pressure or hypertension during
                  screening or previously, exclude for blood pressure that is not well controlled.
                  Well-controlled blood pressure is defined as consistently less than or equal to
                  140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without
                  medication, with only isolated, brief instances of higher readings, which must be
                  less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg
                  diastolic. For these volunteers, blood pressure must be less than or equal to 140
                  mm Hg systolic and less than or equal to 90 mm Hg diastolic at enrollment.

               -  If a person has NOT been found to have elevated blood pressure or hypertension
                  during screening or previously, exclude for systolic blood pressure greater than
                  or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or
                  equal to 100 mm Hg at enrollment.

          -  Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or
             platelet disorder requiring special precautions)

          -  Malignancy (Not excluded from participation: Volunteer who has had malignancy excised
             surgically and who, in the investigator's estimation, has a reasonable assurance of
             sustained cure, or who is unlikely to experience recurrence of malignancy during the
             period of the study)

          -  Seizure disorder: History of seizure(s) within past 3 years. Also exclude if volunteer
             has used medications in order to prevent or treat seizure(s) at any time within the
             past 3 years.

          -  Asplenia: any condition resulting in the absence of a functional spleen

          -  History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.