Evaluating the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults

This study will evaluate the safety, tolerability, and serum concentrations of a human
monoclonal antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and
routes to healthy, HIV-uninfected adults.

Participants will be randomly assigned to one of six groups. Participants in Group 1 will
receive 2.5 mg/kg of VRC07-523LS by intravenous (IV) infusion at Weeks 0, 16, 32, 48, and 64.
Participants in Group 2 will receive 5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16,
32, 48, and 64. Participants in Group 3 will receive 20 mg/kg of VRC07-523LS by IV infusion
at Weeks 0, 16, 32, 48, and 64. Participants in Group 4 will receive 2.5 mg/kg of VRC07-523LS
by subcutaneous (SC) injection at Weeks 0, 16, 32, 48, and 64. Participants in Group 5 will
receive 5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64. Participants
in Group 6 will receive 2.5 mg/kg of VRC07-523LS or placebo by intramuscular (IM) injection
at Weeks 0, 16, 32, 48, and 64.

Participants will attend numerous study visits throughout the course of the study, beginning
at Week 0 through Week 112. 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 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 study product administration with verbal
demonstration of understanding of all questionnaire items answered incorrectly

- Agrees not to enroll in another study of an investigational research agent until
completion of the last required 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 those criteria through the last required protocol
clinic visit (see the protocol for more information).

Laboratory Inclusion Values

Hemogram/Complete Blood Count (CBC)

- Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were assigned female
sex at birth, greater than or equal to 13.0 g/dL for volunteers who were assigned male
sex at birth. For transgender participants who have been on hormone therapy for more
than 6 consecutive months, determine hemoglobin eligibility based on the gender with
which they identify (ie, a transgender female who has been on hormone therapy for more
than 6 consecutive months should be assessed for eligibility using the hemoglobin
parameters for volunteers assigned female sex at birth).

- White blood cell (WBC) count equal to 2,500 to 12,000 cells/mm^3

- WBC 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) less than 1.25 times the institutional
upper limit of normal and creatinine less than or equal to institutional upper limits
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) or chemiluminescent
microparticle immunoassay (CMIA). Non-US sites may use locally available assays that
have been approved by HVTN and HIV Prevention Trials Network (HPTN) Laboratory
Operations.

- 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

- Negative or trace urine protein

Reproductive Status

- Volunteers who were assigned female sex at birth: negative serum or urine beta human
chorionic gonadotropin (β-HCG) pregnancy test performed prior to study product
administration on the day of initial study infusion/injection. 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 assigned female sex at birth must:

- Agree to use effective contraception (see protocol for more information) for
sexual activity that could lead to pregnancy from at least 21 days prior to
enrollment through 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 127/HPTN 087 Protocol Safety
Review Team (PSRT)

- Successful vasectomy in any partner assigned male sex at birth (considered
successful if a volunteer reports that a partner assigned male sex at birth 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 plan to be sexually abstinent until at least 6 months following the last study
product administration.

- Volunteers who were assigned female sex at birth 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

- Weight greater than 115 kg

- Blood products received within 120 days before first study product administration,
unless eligibility for earlier enrollment is determined by the HVTN 127/HPTN 087 PSRT

- Investigational research agents received within 30 days before first study product
administration

- Intent to participate in another study of an investigational research agent or any
other study that requires non-Network HIV antibody testing during the planned duration
of the HVTN 127/HPTN 087 study

- Pregnant or breastfeeding

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 127/HPTN 087 PSRT will determine
eligibility on a case-by-case basis.

- Previous receipt of humanized or human mAbs, whether licensed or investigational; the
HVTN 127/HPTN 087 PSRT will determine eligibility on a case-by-case basis.

- Previous receipt of monoclonal antibodies VRC01, VRC01LS, or VRC07-523LS

Immune System

- Immunosuppressive medications received within 30 days before first injection or
infusion (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled
corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or
[4] a single course of oral/parenteral prednisone or equivalent at doses less than 2
mg/kg/day and length of therapy less than 11 days with completion at least 30 days
prior to enrollment)

- Serious adverse reactions to VRC07-523LS formulation components, including history of
anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema,
and/or abdominal pain

- Immunoglobulin received within 90 days before first injection or infusion, unless
eligibility for earlier enrollment is determined by the HVTN 127/HPTN 087 PSRT

- Autoimmune disease (Not excluded from participation: Volunteer with mild, stable and
uncomplicated autoimmune disease that does not require immunosuppressive medication
and that, in the judgment of the site investigator, is likely not subject to
exacerbation and likely not to complicate Solicited and Unsolicited adverse event (AE)
assessments)

- Immunodeficiency

Clinically significant medical conditions

- 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, infusions, or blood draws, including
inability to establish venous access,

- 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 (eg, chronic urticaria or recent injection or infusion
with evidence of residual inflammation) for which signs or symptoms could be
confused with reactions to the study product, or

- Any condition specifically listed among the exclusion criteria.

- 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 Solicited AEs, 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) therapy

- Asthma other than mild or moderate, 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 high dose inhaled corticosteroids, or

- In the past year has had 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 (Not excluded: type 2 cases controlled with diet
alone or a history of isolated gestational diabetes.)

- 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 three 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