Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: PGT121; PGDM1400; 10-1074; VRC07-523LS
Intervention description: 20 mg/kg administered intravenously; 20 mg/kg administered intravenously; 20 mg/kg administered intravenously; 20 mg/kg administered intravenously
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 27.0
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, pharmacokinetics, and
      antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 10-1074, and
      VRC07-523LS administered via intravenous infusion in 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 low risk of HIV exposure through the last
             required protocol clinic visit (see the protocol for more information)

        Laboratory Inclusion Values

        Hemogram/Complete Blood Count

          -  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 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 count equal to 2,500 to 12,000 cells/mm^3

          -  White blood cell (WBC) differential either within institutional normal range or with
             site clinician 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; 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 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 (β-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 one of 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,

               -  Any other contraceptive method approved by the HVTN 130/HPTN 089 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 or 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 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 130/HPTN 089 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 130/HPTN 089 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 130/HPTN 089 PSRT will determine
             eligibility on a case-by-case basis.

          -  Previous receipt of humanized or human mAbs, whether licensed or investigational; the
             HVTN 130/HPTN 089 PSRT will determine eligibility on a case-by-case basis.

          -  Previous receipt of monoclonal antibodies VRC01, VRC01LS, VRC07-523LS, PGT121,
             PGDM1400, or 10-1074

        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
             less than 20 mg/day and length of therapy less than 14 days.)

          -  Serious adverse reactions to VRC07-523LS, PGT121, PGDM1400, or 10-1074 formulation
             components (acetate, sucrose, polysorbate 80, histidine, and sorbitol; see the
             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 study product administration,
             unless eligibility for earlier enrollment is determined by the HVTN 130/HPTN 089 PSRT
             (for mAb see criterion above)

          -  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 or sub-cutaneous 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 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 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 exclusionary: 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 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 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