Evaluating the Safety and Immunogenicity of an HIV Vaccine (gp145 C.6980) in Healthy, HIV-Uninfected Adults in the United States
Evaluating the Safety and Immunogenicity of an HIV Vaccine (gp145 C.6980) in Healthy, HIV-Uninfected Adults in the United States
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.
This study will 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.

 Participants will be randomly assigned to one of three groups. Participants in Group 1 will
 receive 300 mcg of gp145 C.6980 and aluminum hydroxide adjuvant on Day 0 and Months 2 and 6.
 Participants in Group 2 will receive 100 mcg of gp145 C.6980 and aluminum hydroxide adjuvant
 on Day 0 and Months 2 and 6. Participants in Group 3 will receive placebo on Day 0 and Months
 2 and 6.

 Study visits will occur at Day 0 (study entry), Weeks 1 and 2, and Months 2, 2.5, 6, 6.25,
 6.5, 9, and 12. Visits may include physical examinations, blood and urine collection, HIV
 testing, risk reduction counseling, and questionnaires.
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.