| Eligibility |
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 low risk of HIV exposure through the last
required protocol clinic visit (see study protocol).
Laboratory Inclusion Values:
Hemogram/Complete Blood Count
- Hemoglobin =11.0 g/dL for participants who were assigned female sex at birth, =13.0
g/dL for participants who were assigned male sex at birth. For transgender
participants who have been on feminizing 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 persons
assigned female sex at birth).
- White blood cell (WBC) count = 2,500 to 12,000 cells/mm^3
- WBC differential either within institutional normal range or with site clinician
approval
- Platelets = 125,000 to 550,000 cells/mm^3
Chemistry
- Chemistry panel: alanine aminotransferase (ALT) <1.25 times the institutional upper
limit of normal; creatinine = institutional upper limit of normal
Virology
- Negative HIV-1 and -2 blood test: US volunteers must have a negative Food and Drug
Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent
microparticle immunoassay (CMIA).
- 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 (ß-HCG) pregnancy test performed prior to study product
administration on the day of initial study product administration. 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 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,
- Tubal ligation, or
- Any other contraceptive method approved by the HIV Vaccine Trials Network (HVTN)
136/HIV Prevention Trials Network (HPTN) 092 Protocol Safety Review Team (PSRT)
- Successful vasectomy in any partner assigned male sex at birth (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 be sexually abstinent.
- 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 >115 kg
- Blood products received within 120 days before first study product administration,
unless eligibility for earlier enrollment is determined by the HVTN 136/HPTN 092 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 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 136/HPTN 092 PSRT will determine
eligibility on a case-by-case basis.
- Previous receipt of humanized or human mAbs, whether licensed or investigational; the
HVTN 136/HPTN 092 PSRT will determine eligibility on a case-by-case basis.
- Previous receipt of monoclonal antibodies VRC01, VRC01LS, VRC07-523LS, or PGT121
Immune System
- Immunosuppressive medications received within 30 days before first study product
administration (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled
corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatological
condition; or [4] a single course of oral/parenteral prednisone or equivalent at doses
<20 mg/day and length of therapy <14 days.)
- Serious adverse reactions to VRC07-523LS or PGT121.414.LS formulation components
(acetate, sucrose, polysorbate 80, histidine, and sorbitol; see study protocol),
including history of anaphylaxis and related symptoms such as hives, respiratory
difficulty, angioedema, and/or abdominal pain
- Immunoglobulin received within 90 days before first study product administration,
unless eligibility for earlier enrollment is determined by the HVTN 136/HPTN 092 PSRT
(for mAb see criterion above)
- Autoimmune disease (Not excluded from participation: Participant 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 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 infusions, or blood draws, including inability
to establish venous or subcutaneous 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 skin condition (eg, tattoos) that, in the
judgment of the investigator, would interfere with, or serve as a contraindication to,
protocol adherence, assessment of safety, Solicited AEs, or a participant'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, 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 (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 =140 mm Hg systolic and
=90 mm Hg diastolic, with or without medication, with only isolated, brief
instances of higher readings, which must be =150 mm Hg systolic and =100 mm Hg
diastolic. For these volunteers, blood pressure must be =140 mm Hg systolic and
=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 =150 mm Hg at
enrollment or diastolic blood pressure =100 mm Hg at enrollment.
- Bleeding disorder diagnosed by a clinician (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 generalized urticaria, angioedema, or anaphylaxis.
|
