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HIV InfectionsPhase 1NCT03618056

Evaluating HIV-1 Neutralization Antibody Breadth in Response to HIV gp120 Protein Vaccine in HIV-uninfected Adults With Quiescent Systemic Lupus Erythematosus

A Phase 1 study testing AIDSVAX® B/E in people with HIV Infections and Systemic Lupus Erythematosus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the breadth and potency of HIV-1 neutralizing antibody (nAb) responses and examine the safety and tolerability of an HIV gp120 protein vaccine (AIDSVAX® B/E) in HIV-uninfected adults diagnosed with Systemic Lupus Erythematosus (SLE) who have stable disease. Read more about this study

Who is it for?
Ages 18 to 50 years
Conditions the study is for
HIV Infections, Systemic Lupus Erythematosus
What is being tested?
AIDSVAX® B/E
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
19 Dec 2018to 17 Jul 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • General and Demographic Criteria
  • Age of 18 to 50 years
  • Weight greater than 110 pounds
  • Meets American College of Rheumatology (ACR) criteria for the classification of SLE with serologic evidence of disease including a positive test for antinuclear antibodies at a titer of 1:640 or greater, or the presence of a positive test for antibodies to double-strand DNA (dsDNA), or the presence of anti-Sm, anti-RNP, or anti-Ro antibodies, as documented by medical records and as assessed by a rheumatologist or designee.
  • Currently taking hydroxychloroquine for SLE and for at least 6 months prior to enrollment
  • 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
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  • Ability and willingness to provide informed consent
  • Allows ongoing access to medical records pertaining to their rheumatologic disease
  • 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 before the last required protocol clinic visit
  • 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 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 12.0 g/dL for volunteers who were assigned male sex at birth.
  • White blood cell count equal to 2,500 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 100,000 to 550,000/mm^3
  • Chemistry
  • Chemistry panel: alanine amino transferase (ALT) and aspartate aminotransferase (AST) 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: volunteers must have a negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) within 56 days prior to enrollment.
  • Negative Hepatitis B surface antigen (HBsAg) within 56 days prior to enrollment
  • Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive within 56 days prior to enrollment
  • Urine
  • Normal urine by urinalysis:
  • Negative urine glucose, and
  • Negative or trace urine protein, and
  • Red blood cell (RBC) levels within institutional normal range, and
  • No RBC casts
  • Reproductive Status
  • Volunteers who were assigned female sex at birth: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test in accordance with local regulatory requirements, 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 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, or
  • Any other contraceptive method approved by the HVTN 121 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, bilateral oophorectomy, or tubal ligation;
  • 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

Who cannot join

  • General
  • Blood products received within 120 days before first vaccination
  • Investigational research agents not used to treat SLE received within 30 days before first vaccination (additional exclusions may apply, see criteria below)
  • 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 121 study
  • Pregnant or breastfeeding
  • Active duty and reserve US military personnel
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  • SLE status. The following criteria must be verified by a rheumatologist or designee
  • Currently with active lupus as defined by a Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) greater than 4 (see protocol for more information).
  • Documented SLEDAI score of greater than 20 in medical record at any time indicating severe activity, or evidence of moderate disease activity (SELENA-SLEDAI greater than 6) within the last six months, (see protocol for more information).
  • Has had a condition listed on the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) or has had an increase in the SLICC/ACR D1 score within the last 12 months other than cataracts, premature ovarian failure or diabetes mellitus with approval of the PSRT http://www.clinexprheumatol.org/article.asp?a=2697
  • A history of central nervous system (CNS) disease
  • Thrombotic event within the past 12 months in association with confirmed antiphospholipid antibody
  • A history of renal disease (SLE-related renal injury) confirmed by prior biopsy, active urine sediment, or proteinuria
  • Prednisone dose greater than 10 mg/day for more than 6 months within the past year
  • Administration of anti-B-cell therapy (rituximab or belimumab) or any investigational research agents used to treat SLE within the preceding 2 years
  • Administration of cyclophosphamide within the preceding year; or administration of mycophenolate mofetil within the last 6 months; or administration of methotrexate, leflunomide, or azathioprine within the last 3 months
  • Administration of any investigational immunosuppressant medication within the last year
  • Administration of other immunosuppressive medications not listed above, with the exception of topical steroids, topical immunosuppressives (eg, cyclosporine, FK506), or ophthalmic immunosuppressives (eg, steroids, cyclosporine), within 6 months before first vaccination, unless approved by the HVTN 121 PSRT
  • 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 121 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 by the HVTN 121 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 121 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 121 PSRT on a case-by-case basis.
  • Vaccines received within 30 days before first study vaccination or scheduled within 30 days after injection (eg, influenza, tetanus, pneumococcal, Hepatitis A or B, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)
  • Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
  • Immune System
  • Serious adverse reactions to vaccines or to vaccine components (such as yeast protein, amorphous aluminum hydroxyphosphate sulfate, L-histidine, polysorbate 80, sodium borate), 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
  • Immunodeficiency, such as common variable immunodeficiency
  • Clinically significant medical conditions
  • Ongoing bleeding or hemorrhage (excluding menstruation), or any subject on anticoagulant therapy
  • Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health, other than SLE and its manifestations. 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 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 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.
  • Uncontrolled diabetes mellitus, Hb A1C greater than 7.0. (not excluded: history of isolated gestational diabetes.)
  • Uncontrolled hypertension:
  • If a person has a history of hypertension, or is found to have elevated blood pressure or hypertension during screening, 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 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 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 (not excluded: splenectomy for splenic trauma)
  • History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke Human Vaccine Institute CRS

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: A Phase 1b Open Label Clinical Trial to Evaluate HIV-1 Neutralization Antibody Breadth in Response to HIV gp120 Protein Vaccine in HIV-uninfected Adults With Quiescent Systemic Lupus Erythematosus

The purpose of this study is to evaluate the breadth and potency of HIV-1 neutralizing antibody (nAb) responses and examine the safety and tolerability of an HIV gp120 protein vaccine (AIDSVAX® B/E) in HIV-uninfected adults diagnosed with Systemic Lupus Erythematosus (SLE) who have stable disease.

Read the detailed description

This study will evaluate the breadth and potency of HIV-1 neutralizing antibody (nAb) responses and examine the safety and tolerability of an HIV gp120 protein vaccine (AIDSVAX® B/E) in HIV-uninfected adults diagnosed with Systemic Lupus Erythematosus (SLE) who have stable disease.

All participants will receive 600 mcg/mL of AIDSVAX® B/E at Months 0, 1, and 6.

Study visits will occur at Months 0, 0.25, 0.5, 1, 1.25, 1.5, 3, 6, 6.25, 6.5, 7.5, 8.5, and 12. Visits may include physical examinations, blood and urine collection, pregnancy testing, HIV testing, risk reduction counseling, assessments, and questionnaires.

Being tested
AIDSVAX® B/E
Medical subject headings
HIV Infections, Lupus Erythematosus, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AIDSVAX® B/EBiological

    Administered by intramuscular injection

Study groups in NCT03618056
Study groupRoleWhat they receive
AIDSVAX® B/EExperimentalParticipants will receive 600 mcg/mL of AIDSVAX® B/E at Months 0, 1, and 6.
Receives: Biological: AIDSVAX® B/E

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Response Rates of nAb Responses to the Vaccine Strains and a Global Panel of Heterologous Env-pseudotyped Viruses

    Assessed by TZM-bl assay

    Measured: Measured through Month 6.5

  2. Change in Magnitude of nAb Responses to the Vaccine Strains and a Global Panel of Heterologous Env-pseudotyped Viruses

    Assessed by TZM-bl assay

    Measured: Measured through Month 6.5

  3. Breadth of nAb Responses to the Vaccine Strains and a Global Panel of Heterologous Env-pseudotyped Viruses

    Assessed by TZM-bl assay

    Measured: Measured through Month 6.5

  4. Number of Participants With Local Reactogenicity Signs and Symptoms, Stratified by Severity

    Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July, 2017. The maximum grade observed for each symptom over the time frame is presented.

    Measured: Measured for seven days through participant's last vaccination at Month 0,1,and 6

  5. Number of Participants With Systemic Reactogenicity Signs and Symptoms, Stratified by Severity

    Graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July, 2017. The maximum grade observed for each symptom over the time frame is presented.

    Measured: Measured for seven days through participant's last vaccination at Month 0,1,and 6

  6. Number of Participants With Adverse Events, by Relationship to the Study Product

    AEs categorized by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class, and MedDRA Preferred Term. For participants reporting multiple AEs over the time frame, the maximum relationship is counted.

    Measured: Measured through Month 12

  7. Number of Participants With SLE Disease Activity and Functional Status Scores, by Score and Study Day

    As assessed by Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) and Routine Assessment of Patient Index Data (RAPID3). The SELENA-SLEDAI is used to assess disease activity across nine organ systems within 10 days prior up to and including the day of study visit. The SELENA-SLEDAI is reported as a a weighted composite score with a range from 0 (no evidence of disease; best outcome) to 105 (extremely severe disease). The RAPID3 is a pooled index of the 3 patient-reported American College of Rheumatology rheumatoid arthritis (RA) Core Data Set measures: function, pain, and patient global estimate of status. Each of the 3 individual measures is scored 0 to 10, for a total of 30. Disease severity was classified on the basis of RAPID3 scores: >12 = high severity; 6.1-12 = moderate; 3.1-6 = low; < or =3 = near remission (best outcome).

    Measured: Measured at all study visits completed in person through Month 12. Per protocol, the assessments were administered at Screening, Day 0 (date of first vaccination), Day 7, Day 14, Day 35, Day 42, Day 84, Day 168, Day 175, Day 182, Day 238, and Day 364.

Secondary outcomes (10)

  1. Changes in Somatic Hypermutation in Participants With SLE Compared With Historical Controls

    Measured by flow cytometry

    Measured: Measured through Month 6.5

  2. Change in Length of Antibody Binding Loops and Germline Gene Usage in Participants With SLE Compared With Historical Controls

    Measured by flow cytometry

    Measured: Measured through Month 6.5

  3. Change in NAb Responses to Viruses With Altered Glycosylation, Indicative of bnAb Precursors

    Assessed by TZM-bl assay

    Measured: Measured through Month 6.5

  4. Change in Vaccine-induced Immune Activation

    Assessed by serum cytokine analysis and B and T cell phenotyping, as well as expression of Treg and Tfh markers

    Measured: Measured through Month 6.25

  5. Change in Response Rate of HIV-1-Specific IgG Binding Antibodies

    Assessed by Binding Antibody Multiplex Assay (BAMA)

    Measured: Measured through Month 6.5

  6. Change in Magnitude of HIV-1-Specific IgG Binding Antibodies

    Assessed by BAMA

    Measured: Measured through Month 6.5

  7. Change in Specificity of Antibody Responses

    Assessed by epitope mapping of functional and binding antibodies

    Measured: Measured through Month 6.5

  8. Change in Response Rate of Env-specific CD4+ T Cells

    Measured by intracellular cytokine staining (ICS)

    Measured: Measured through Month 6.5

  9. Change in Magnitude of Env-specific CD4+ T Cells

    Measured by ICS

    Measured: Measured through Month 6.5

  10. Change in Polyfunctionality of Env-specific CD4+ T Cells

    Measured by ICS

    Measured: Measured through Month 6.5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2018
  2. Study start19 Dec 2018
  3. Primary completion17 Jul 2020
  4. Study completion17 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03618056
Sponsor's protocol ID
HVTN 121
Other IDs
38162
Status last verified
Jan 2022
First submitted
1 Aug 2018
Last updated
7 Feb 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AIDSVAX® B/E in people with HIV Infections and Systemic Lupus Erythematosus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 46 inclusion and 54 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Response Rates of nAb Responses to the Vaccine Strains and a Global Panel of Heterologous Env-pseudotyped Viruses (time frame: Measured through Month 6.5). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03618056.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2022.

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