Clinical trial NCT02852005: Evaluating the Immunogenicity of the AIDSVAX B/E Vaccine and the MVA/HIV62B Vaccine in Healthy, HIV-1-Uninfected Adults Who Previously Received MVA/HIV62B in DNA/MVA or MVA/MVA Regimens in HVTN 205
Official title: A Phase 1 Clinical Trial to Evaluate the Immunogenicity of AIDSVAX B/E Bivalent gp120 Vaccine and MVA/HIV62B in Healthy, HIV-1-Uninfected Adult Participants Who Previously Received MVA/HIV62B in DNA/MVA or MVA/MVA Regimens in HVTN 205
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: 2016-08-02
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
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, tolerability, and immunogenicity of the AIDSVAX B/E vaccine and the MVA/HIV62B vaccine in healthy, HIV-1-uninfected adults who previously received MVA/HIV62B in DNA/MVA or MVA/MVA vaccine regimens in the HVTN 205 study.

Detailed description: This study will evaluate the safety, tolerability, and immunogenicity of the AIDSVAX B/E vaccine and the MVA/HIV62B vaccine in healthy, HIV-1-uninfected adults who previously received MVA/HIV62B in DNA/MVA or MVA/MVA vaccine regimens as part of the HVTN 205 study.

Participants in this study will be assigned to one of five groups based on their previous vaccine regimen received in HVTN 205. Depending on their group, participants will receive the MVA/HIV62B vaccine, the AIDSVAX B/E vaccine, or both the MVA/HIV62B vaccine and the AIDSVAX B/E vaccine. All participants will receive their assigned vaccines at study entry (Day 0) and Month 4. Participants will attend several study visits through Month 10. Visits will include physical examinations, blood collection, HIV testing and risk reduction counseling, and interviews and questionnaires. Optional procedures at some visits include collection of rectal fluids, cervical fluids, and semen. Study staff will contact participants 2 years following the initial study injection for follow-up health monitoring.

Eligibility criteria: Inclusion Criteria:

General and Demographic Criteria:

* Age of 18 to 55 years
* Prior participation in HVTN 205 with assignment to treatment (not placebo) arm:

  1. Assigned to HVTN 205 Group 1 or Group 3, and received all 4 scheduled vaccinations (2 injections of pGA2/JS7 DNA (months 0, 2) and 2 injections of MVA/HIV62 (months 4, 6); OR
  2. Assigned to HVTN 205 Group 4, and received at least vaccinations 1, 2 and 4 (3 injections of MVA/HIV62 at months 0, 2 and 6).
* Access to a participating 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
* Willing to be contacted 2 years following initial study injection.
* Agrees not to enroll in another study of an investigational research agent
* 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.

Laboratory Inclusion Values:

Hemogram/Complete Blood Count (CBC)

* Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
* White blood cell count equal to 3,300 to 12,000 cells/mm\^3
* Total lymphocyte count greater than or equal to 800 cells/mm\^3
* Remaining 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), aspartate aminotransferase (AST), and alkaline phosphatase less than 1.25 times the institutional upper limit of normal; creatinine less than or equal to institutional upper limit of normal.
* Cardiac Troponin T or I (cTnT or cTnI) does not exceed the institutional upper limit of normal

Virology

* Negative HIV-1 and -2 blood test: Participants must have a negative test result for HIV infection following the HVTN Lab Program's in-study HIV testing algorithm, prior to initial enrollment.
* Negative hepatitis B surface antigen (HBsAg)
* Negative anti-hepatitis C virus Ab (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive

Urine

* Normal urine:

  * Negative urine glucose, and
  * Negative or trace urine protein, and
  * Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range).

Reproductive Status

* Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of initial vaccination. 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 born female must:

  * Agree to consistently use effective contraception (more information is available in the protocol) 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 114 Protocol Safety Review Team (PSRT)
  * Successful vasectomy in the male partner (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, bilateral oophorectomy, or tubal ligation;
  * Or be sexually abstinent.
* Volunteers who were born female 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
* Volunteer has 2 or more of the following cardiac risk factors:

  * Participant report of history of elevated blood cholesterol defined as fasting LDL greater than 160 mg/dL;
  * First degree relative (eg, mother, father, brother, or sister) who had coronary artery disease before the age of 50 years;
  * Current smoker; or
  * BMI greater than or equal to 35
* Pregnant or breastfeeding
* Active duty and reserve U.S. military personnel

Vaccines and Other Injections

* Any clinically significant AE related to vaccination in HVTN 205, for which revaccination would be a safety concern such as any grade 3 or 4 related AE
* Smallpox vaccine received within the last 5 years
* HIV vaccine(s) received in a prior HIV vaccine trial other than HVTN 205. For HVTN 205 participants who have subsequently received control/placebo in another HIV vaccine trial, the HVTN 114 PSRT will determine eligibility on a case-by-case basis.
* Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 114 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 114 PSRT on a case-by-case basis.
* Live attenuated vaccines other than influenza vaccine 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)
* Influenza vaccine or 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 dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses less than 2 mg/kg/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.)
* Hypersensitivity to eggs or egg products
* Immunoglobulin received within 60 days before first vaccination
* Autoimmune disease (eg, myositis)
* Immunodeficiency

Cardiac

* History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow-up)
* ECG with clinically significant findings, or features that would interfere with the assessment of myo/pericarditis, as determined by a contract ECG Lab or cardiologist, including any of the following: (1) conduction disturbance (complete left or complete right bundle branch block or nonspecific intraventricular conduction disturbance with QRS greater than or equal to 120 ms, PR interval greater than or equal to 220ms, any 2nd or 3rd degree AV block, or QTc prolongation (greater than 450ms)); (2) repolarization (ST segment or T wave) abnormality that will interfere with the assessment of myo/pericarditis; (3) significant atrial or ventricular arrhythmia; (4) frequent atrial or ventricular ectopy (eg, frequent premature atrial contractions, 2 premature ventricular contractions in a row); (5) ST elevation consistent with ischemia; (6) evidence of past or evolving myocardial infarction

Clinically Significant Medical Conditions

* Untreated or incompletely treated syphilis infection
* 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
* 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 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, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)
* Thyroidectomy, or thyroid disease requiring medication during the last 12 months
* 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 3 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.

Primary outcomes:
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms of the Left Arm (MVA/HIV62B or Placebo)
timeFrame: Measured through 3 days after the boost at Month 0 and Month 4
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms of the Right Arm (AIDSVAX B/E or Placebo)
timeFrame: Measured through 3 days after the boost at Month 0 and Month 4
measure: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms During the Boost Regimen
timeFrame: Measured through Month Measured through 3 days after each boost at Month 0 and 4
measure: Number of Participants With Early Study Termination Associated With an AE or Reactogenicity
timeFrame: Measured through Month 10
measure: Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity
timeFrame: Measured through the Month 4 boost
measure: Chemistry and Hematology Laboratory Measures, for Each Boost: Alkaline Phosphatase, AST, ALT in U/L
timeFrame: Measured during screening, and 2 weeks after each boost at Month 0 and 4
measure: Chemistry and Hematology Laboratory Measures, for Each Boost: Hemoglobin, Creatinine in g/dL
timeFrame: Measured during screening, and 2 weeks after each boost at Month 0 and 4
measure: Chemistry and Hematology Laboratory Measures, for Each Boost: WBC, Platelets, Lymphocytes, Neutrophils
timeFrame: Measured during screening, and 2 weeks after each boost at Month 0 and 4
measure: Occurrence of Env-specific IgG Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost
timeFrame: Measured at Month 0.5 and 4.5
measure: Level of Env-specific IgG Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost
timeFrame: Measured at Month 0.5 and 4.5
measure: Occurrence of Env-specific IgG3 Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost
timeFrame: Measured at Month 0.5 and 4.5
measure: Level of Env-specific IgG3 Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost
timeFrame: Measured at Month 0.5 and 4.5
measure: Occurrence of Env-specific IgA Responses for gp120, gp41, V1V2, and the IDR of gp41 at 2 Weeks After Each Boost
timeFrame: Measured at Month 0.5 and 4.5
measure: Level of Env-specific IgA Responses for gp120, gp41, V1V2, and the IDR of gp41 at 2 Weeks After Each Boost
timeFrame: Measured at Month 0.5 and 4.5
measure: Occurrence of Neutralizing Ab Titers and Breadth Against the Env Vaccine Strain and Heterologous Tier 1 Strains at 2 Weeks After Each Boost
timeFrame: Measured at Month 0.5 and 4.5
measure: Level of Neutralizing Ab Titers and Breadth Against the Env Vaccine Strain and Heterologous Tier 1 Strains at 2 Weeks After Each Boost
timeFrame: Measured at Month 0.5 and 4.5
Secondary outcomes:
measure: Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost
timeFrame: Measured at Month 4.5
measure: Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost
timeFrame: Measured at Month 4.5
measure: Occurrence of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost
timeFrame: Measured at Month 4.5
measure: Level of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost
timeFrame: Measured at Month 4.5
measure: Occurrence of Env-specific IgG Responses for gp120, gp140, V1/V2, and the IDR of gp41 at 6 Months After the Final Boost
timeFrame: Measured at Month 10
measure: Level of Env-specific IgG Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 6 Months After the Final Boost
timeFrame: Measured at Month 10
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama CRS
state: Alabama
city: San Francisco
country: United States
facility: Bridge HIV CRS
state: California
city: Decatur
country: United States
facility: The Hope Clinic of the Emory Vaccine Center CRS
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
state: Massachusetts
city: New York
country: United States
facility: Columbia P&S CRS
state: New York
city: Rochester
country: United States
facility: University of Rochester Vaccines to Prevent HIV Infection CRS
state: New York
city: Seattle
country: United States
facility: Seattle Vaccine and Prevention CRS
state: Washington
city: Iquitos
country: Peru
facility: ACSA CRS
state: Maynas
city: Lima
country: Peru
facility: Barranco CRS
Study officials:
affiliation: University of Alabama at Birmingham
name: Paul Goepfert
role: STUDY_CHAIR
References:
citation: Huang Y, Seaton KE, Casapia M, Polakowski L, De Rosa SC, Cohen K, Yu C, Elizaga M, Paez C, Miner MD, Kelley CF, Maenza J, Keefer M, Lama JR, Sobieszczyk M, Buchbinder S, Baden LR, Lee C, Gulati V, Sinangil F, Montefiori D, McElrath MJ, Tomaras GD, Robinson HL, Goepfert P; NIAID-funded HIV Vaccine Trials Network (HVTN) 114 Study Team. AIDSVAX protein boost improves breadth and magnitude of vaccine-induced HIV-1 envelope-specific responses after a 7-year rest period. Vaccine. 2021 Jul 30;39(33):4641-4650. doi: 10.1016/j.vaccine.2021.06.066. Epub 2021 Jul 3.
citation: Fischinger S, Cizmeci D, Deng D, Grant SP, Frahm N, McElrath J, Fuchs J, Bart PA, Pantaleo G, Keefer M, O Hahn W, Rouphael N, Churchyard G, Moodie Z, Donastorg Y, Streeck H, Alter G. Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials. PLoS Pathog. 2021 Nov 29;17(11):e1010016. doi: 10.1371/journal.ppat.1010016. eCollection 2021 Nov.