Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women
Condition: HIV Infections
MeSH terms: Infections; Communicable Diseases
Intervention: VRC01; Placebo for VRC01
Intervention description: Administered by IV infusion; total dose will vary based on participant's weight; Sodium Chloride for Injection USP, 0.9%; administered by IV infusion
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1924.0
Sex: Female
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HIV-1 Infections

Summary:

      This study will evaluate the safety and efficacy of the human monoclonal antibody (mAb)
      VRC-HIVMAB060-00-AB (VRC01) in preventing HIV-1 infection in high-risk, HIV-uninfected women.
    

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 infusion with verbal demonstration of
             understanding of all questionnaire items answered incorrectly

          -  Agrees not to enroll in another study of an investigational research agent for the
             duration of the participant's trial participation

          -  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

          -  Persons born Female (assigned female sex at birth) and identifying as a female, who,
             in the 6 months prior to randomization, has had vaginal and/or anal intercourse with a
             male partner

          -  All volunteers who have been in a monogamous relationship with an HIV-1 seronegative
             partner for greater than 1 year are excluded.

        Laboratory Inclusion Values+

        Hematology

          -  Hemoglobin (Hgb) greater than or equal to 10.5 g/dL for volunteers who were born
             female, greater than or equal to 13.0 g/dL for volunteers who were born male

          -  Platelets greater than or equal to 100,000 cells/mm^3

        Chemistry

          -  Alanine aminotransferase (ALT) less than 2.5 times the institutional upper limit of
             normal and creatinine less than or equal to 1.25 times the institutional upper limit
             of normal

        Virology

          -  HIV uninfected, as defined in the study specific procedures (SSP), within 30 days
             prior to enrollment

        Urine

          -  Negative, trace, or 1+ urine protein by dipstick

        Reproductive Status

          -  Volunteers capable of becoming pregnant: negative serum or urine beta human chorionic
             gonadotropin (β-HCG) pregnancy test performed at the screening visit and prior to
             infusion on the day of initial infusion. Persons who are NOT capable of becoming
             pregnant 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 is capable of becoming pregnant must agree to
             consistently use effective contraception (see the protocol and SSP 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.

          -  Volunteers capable of becoming pregnant 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

          -  Investigational research agents received within 30 days before first infusion

          -  Body mass index (BMI) greater than or equal to 40

          -  Pregnant or breastfeeding

          -  Any reactive, indeterminate, or positive HIV test, even if subsequent testing
             indicates that the individual is not HIV infected.

        Monoclonal antibodies and vaccines

          -  Previous receipt of humanized or human monoclonal antibodies (mAbs), whether licensed
             or investigational

          -  HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received
             control/placebo in an HIV vaccine trial, the HVTN 703/HPTN 081 Protocol Safety Review
             Team (PSRT) will determine eligibility on a case-by-case basis.

        Immune System

          -  Serious adverse reactions to VRC01 formulation components such as sodium citrate,
             sodium chloride, and L-arginine hydrochloride, including history of anaphylaxis and
             related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal
             pain.

          -  Autoimmune disease, including Type I diabetes mellitus (Not excluded from
             participation: Volunteer with mild, stable and uncomplicated autoimmune disease that
             does not require consistent immunosuppressive medication and that, in the judgment of
             the site investigator, is likely not subject to exacerbation and likely not to
             complicate reactogenicity and adverse event (AE) assessments)

          -  Immunodeficiency syndrome

        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:

               -  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; or

               -  A condition or process for which signs or symptoms could be confused with
                  reactions to VRC01.

          -  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 infusion reactions, 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.

          -  Asthma, other than mild, well-controlled asthma

          -  Bleeding disorder diagnosed by a doctor (e.g., 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.

          -  History of hereditary angioedema, acquired angioedema, or idiopathic angioedema

          -  History of organ or tissue transplantation

          -  Known hepatic or renal dysfunction