Clinical trial NCT03934541: Evaluating the Safety and Immunogenicity of an HIV-1 gp41 MPER-656 Liposome Vaccine in Healthy, HIV-uninfected Adult Participants
Official title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of an HIV-1 gp41 MPER-656 Liposome Vaccine in Healthy, HIV-uninfected Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2019-05-02
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: This study will evaluate the safety and immunogenicity of an HIV-1 gp41 MPER-656 liposome vaccine in healthy, HIV-uninfected adults.

Participants will be randomly assigned to four groups. Participants in Group 1 (Treatment 1) will receive 500 mcg of MPER-656 liposome vaccine at Months 0, 2, and 6. Participants in Group 1 (Control 1) will receive placebo at Months 0, 2, and 6. Participants in Group 2 (Treatment 2) will receive 2000 mcg of MPER-656 liposome vaccine at Months 0, 2, and 6. Participants in Group 2 (Control 2) will receive placebo at Months 0, 2, and 6. Study staff will review safety data from Group 1 before deciding whether to enroll Group 2.

Participants will attend several study visits through Month 12. Visits may include physical examinations, blood and urine collection, HIV testing, risk reduction counseling, and questionnaires. Study staff will contact participants at Month 18 for follow-up health monitoring.

As of May 2020, vaccinations were discontinued for all participants.

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.)

Primary outcomes:
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
timeFrame: Measured through 7 days after each vaccine dose at Months (0,2,6,12)
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
timeFrame: Measured through 7 days after each vaccine dose at Months (0,2,6,12)
measure: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
timeFrame: Measured through 7 days after each vaccine dose at Months (0,2,6,12)
measure: Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT) in U/L
timeFrame: Measured during screening, Days 14, 70, 182
measure: Chemistry and Hematology Laboratory Measures - Creatinine in mg/dL
timeFrame: Measured during screening, Days 14, 70, 182
measure: Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL
timeFrame: Measured during screening, Days 14, 70, 182
measure: Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count in 1000 Cells/Cubic mm
timeFrame: Measured during screening, Days 14, 70, 182
measure: Chemistry and Hematology Laboratory Measures - Platelets, WBC in 1000 Cells/Cubic mm
timeFrame: Measured during screening, Days 14, 70, 182
measure: The Number (Percentage) of Participants With Lab Grade > 1 for Alanine Aminotransferase (ALT), Creatinine, Hemoglobin, Lymphocyte Count, Neutrophil Count, Platelets, White Blood Cells (WBC) Was Summarized by Arm
timeFrame: Measured during screening, Days 14, 70, 182
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama CRS
state: Alabama
city: Boston
country: United States
facility: Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
state: Massachusetts
city: Boston
country: United States
facility: Fenway Health (FH) CRS
state: Massachusetts
city: New York
country: United States
facility: Columbia P&S CRS
state: New York
city: New York
country: United States
facility: New York Blood Center CRS
state: New York
city: Seattle
country: United States
facility: Seattle Vaccine and Prevention CRS
state: Washington
Study officials:
affiliation: Brigham and Women's Hospital
name: Lindsey Baden
role: STUDY_CHAIR
affiliation: University of Alabama at Birmingham
name: Nathan Erdmann
role: STUDY_CHAIR
References: