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
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: VRC07-523LS; Placebo
Intervention description: Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in; Sodium Chloride for Injection USP, 0.9%; administered by IM injection
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 124.0
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 serum concentrations
      of a human monoclonal antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple
      doses and routes to healthy, HIV-uninfected adults.
    

Eligibility criteria:

        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