Evaluating the Safety and Immunogenicity of an HIV-1 gp41 MPER-656 Liposome Vaccine in Healthy, HIV-uninfected Adult Participants
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: MPER-656 Liposome Vaccine; Placebo for MPER-656 Liposome Vaccine
Intervention description: Administered by intramuscular injection; Administered by intramuscular injection
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 24.0
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 immunogenicity of an HIV-1 gp41
      MPER-656 liposome vaccine in 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;
             completes a questionnaire prior to first vaccination with verbal demonstration of
             understanding of all questionnaire items answered incorrectly

          -  Agrees not to enroll in another study of an investigational research agent while in
             this study

          -  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 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 persons assigned female sex at birth)

          -  White blood cell count equal to 2,500 to 12,000 cells/mm^3 with normal differential,
             or differential approved by Investigator of Record (IoR) as not clinically significant

          -  Total lymphocyte count greater than or equal to 650 cells/mm^3 with normal
             differential, or differential approved by IoR as not clinically significant

          -  Remaining differential either within institutional normal range or with site physician
             approval

          -  Platelets equal to 125,000 to 550,000 cells/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 1.1 times the institutional
             upper limit of normal

        Clotting and autoantibodies

          -  Anticardiolipin IgG antibodies below the upper limit of normal

          -  Negative antinuclear antibodies

        Virology

          -  Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-approved
             enzyme immunoassay (EIA)

          -  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

          -  Normal urine:

               -  Negative or trace urine protein, and

               -  Negative, trace, or 1+ blood urine hemoglobin (if +1 hemoglobin is present on
                  dipstick, a microscopic urinalysis with red blood cells levels within
                  institutional normal range)

        Reproductive Status

          -  Volunteers who were assigned female sex at birth: negative serum or urine beta human
             chorionic gonadotropin (β-HCG) pregnancy test at screening (ie, prior to
             randomization) and prior to study product administration on the day of study product
             administration. Persons who are NOT of reproductive potential due to having undergone
             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 HVTN 133 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

          -  Blood products received within 120 days before first vaccination

          -  Investigational research agents received within 30 days before first vaccination

          -  Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35
             with 2 or more of the following: age greater than 45, systolic blood pressure greater
             than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, known
             hyperlipidemia

          -  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 HVTN 133 study

          -  Pregnant or breastfeeding

          -  Active duty and reserve US military personnel

        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 133 PSRT will determine eligibility
             on a case-by-case basis.

          -  Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational;
             the HVTN 133 PSRT will determine eligibility on a case-by-case basis.

          -  Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine
             trial. Exceptions may be made by the HVTN 133 PSRT for vaccines that have subsequently
             undergone licensure by the FDA. For volunteers who have received control/placebo in an
             experimental vaccine trial, the HVTN 133 PSRT will determine eligibility on a
             case-by-case basis. For volunteers who have received an experimental vaccine(s)
             greater than 1 year ago, eligibility for enrollment will be determined by the HVTN 133
             PSRT on a case-by-case basis.

          -  Live attenuated vaccines received within 30 days before first vaccination or scheduled
             within 14 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio
             vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine)

          -  Any vaccines that are not live attenuated vaccines and were received within 14 days
             prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)

          -  Allergy treatment with antigen injections within 30 days before first vaccination or
             that are scheduled within 14 days after first vaccination

        Immune System

          -  Immunosuppressive medications received within 168 days before first vaccination (Not
             exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical
             corticosteroids for mild, uncomplicated dermatologic condition; or [4] a single course
             of oral/parenteral prednisone or equivalent at doses less than or equal to 60 mg/day
             and length of therapy less than 11 days with completion at least 30 days prior to
             enrollment)

          -  Serious adverse reactions to vaccines or to vaccine components including history of
             anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema,
             and/or abdominal pain. (Not excluded from participation: a volunteer who had a
             nonanaphylactic adverse reaction to pertussis vaccine as a child.)

          -  Immunoglobulin received within 60 days before first vaccination (for mAb see criterion
             above)

          -  Autoimmune disease, current or history, (Not exclusionary: mild, wellcontrolled
             psoriasis)

          -  Adverse event of special interest (AESIs): Volunteers who currently have, or have a
             history of any condition that could be considered an AESI for the products
             administered in this protocol (representative examples are listed in the study
             protocol)

          -  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 or blood draws,

               -  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 for which signs or symptoms could be confused with
                  reactions to vaccine, 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 or reactogenicity, or a volunteer's ability to give
             informed consent

          -  Any contraindication that would preclude injections into both left and right deltoids

          -  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) prophylaxis or therapy

          -  Asthma exclusion criteria: 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.)

          -  Thyroidectomy, or thyroid disease requiring medication during the last 12 months (Not
             exclusionary: well-controlled non-autoimmune thyroid disease)

          -  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 in this protocol as consistently less
                  than 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 (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 generalized urticaria, angioedema, or anaphylaxis. (Not exclusionary:
             angioedema or anaphylaxis to a known trigger with at least 5 years since last reaction
             to demonstrate satisfactory avoidance of trigger.)