Evaluating the Safety and Pharmacokinetics of VRC07-523LS in the Sera and Mucosae of Healthy, HIV-Uninfected Adult Participants
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: VRC07-523LS
Intervention description: Administered by intravenous (IV) infusion
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 28.0
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 and pharmacokinetics of a human
      monoclonal antibody (VRC07-523LS) in the sera and mucosae of healthy, HIV-uninfected adults.
    

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 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 the study protocol for US Low risk guidelines.

        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 feminizing 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 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).

          -  Negative Hepatitis B surface antigen (HBsAg)

          -  Negative anti-Hepatitis C virus (anti-HCV) antibodies, or negative HCV polymerase
             chain reaction (PCR) if the anti-HCV is positive

        Urine

          -  Normal 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 biopsy collection
             and/or study product administration.

          -  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, or

                    -  Any other contraceptive method approved by the HVTN 128 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);

                    -  Tubal ligation

               -  Or be sexually abstinent until at least 4 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

        Mucosal Specimen Collection

          -  Volunteers 21 years of age and older who were assigned female sex at birth: Pap smear
             (verified by medical records) is required within:

               -  the 3 years prior to enrollment with the latest result reported as normal or
                  ASCUS (atypical squamous cells of undetermined significance), OR

               -  the 5 years prior to enrollment, with the latest result reported as normal, or
                  ASCUS with no evidence of high risk HPV.

          -  If no Pap smear was done within the last 3 years (or within the last 5 years, if high
             risk HPV testing was performed), the volunteer must be willing to undergo a Pap smear
             with the result reported (verified by medical records) as normal or ASCUS prior to
             sample collection.

          -  Willing to have mucosal secretions and tissue biopsies collected at several timepoints

          -  Willing to abstain from sexual intercourse for the required period after each biopsy
             collection

        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 128 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-HVTN 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 128 PSRT will determine eligibility
             on a case-by-case basis.

          -  Previous receipt of humanized or human monoclonal antibodies (mAbs), whether licensed
             or investigational; the HVTN 128 PSRT will determine eligibility on a case-by-case
             basis.

          -  Previous receipt of monoclonal antibodies against HIV

        Immune System

          -  Immunosuppressive medications received within 30 days before first 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 or equal to 20 mg/day and
             length of therapy less than 14 days)

          -  Serious adverse reactions to VRC07-523LS formulation components (sucrose, histidine,
             and sorbitol; see study protocol for more information), including history of
             anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema,
             and/or abdominal pain.

          -  Immunoglobulin received within 90 days before first infusion unless eligibility for
             earlier enrollment is determined by the HVTN 128 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 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 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 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 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, 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, 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 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.

        Mucosal Specimen Collection

          -  A rectal condition (for rectal biopsies), such as an active infection or inflammation
             of the colorectal area (eg, an HSV-2 outbreak or inflamed hemorrhoids or
             colitis/diarrhea), internal hemorrhoids, or any other condition noted during screening
             rectal exam via anoscope or in medical history that in the opinion of the clinician
             represents a contraindication to mucosal sampling.

          -  For those who were assigned female sex at birth (for vaginal and cervical biopsies),
             any condition noted during pelvic exam via speculum or in medical history that in the
             opinion of the clinician represents a contraindication to mucosal sampling (eg,
             bacterial vaginosis).

          -  An active genital tract condition, such as an active infection or inflammation of the
             genital tract (eg, genital sores or ulcers, penile or abnormal vaginal discharge,
             genital warts that are symptomatic or requiring treatment) or any other condition that
             in the opinion of the clinician represents a contraindication to mucosal sampling.

          -  Hysterectomy or bilateral oophorectomy

          -  Menopause

          -  Current use of anticoagulants