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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 February 2022
• Main ID: NCT03618056
• Date of registration: 01/08/2018
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Evaluating HIV-1 Neutralization Antibody Breadth in Response to HIV gp120 Protein Vaccine in HIV-uninfected Adults With Quiescent Systemic Lupus Erythematosus
• Scientific 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
• Date of first enrolment: December 19, 2018
• Target sample size: 1
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03618056
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Prevention. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: M. Anthony Moody
• Affiliation: Duke University

• Name: Paul Goepfert
• Affiliation: University of Alabama at Birmingham

Key inclusion & exclusion criteria

Inclusion Criteria:

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

- 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 (ß-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

Exclusion Criteria:

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

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


Age minimum: 18 Years
Age maximum: 50 Years
Gender: All

Health Condition(s) or Problem(s) studied

HIV Infections

Systemic Lupus Erythematosus

Intervention(s)

Biological: AIDSVAX® B/E

Primary Outcome(s)

Breadth of nAb Responses to the Vaccine Strains and a Global Panel of Heterologous Env-pseudotyped Viruses [Time Frame: Measured through Month 6.5]

Number of Participants With Adverse Events, by Relationship to the Study Product [Time Frame: Measured through Month 12]

Change in Magnitude of nAb Responses to the Vaccine Strains and a Global Panel of Heterologous Env-pseudotyped Viruses [Time Frame: Measured through Month 6.5]

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]

Number of Participants With SLE Disease Activity and Functional Status Scores, by Score and Study Day [Time Frame: 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.]

Number of Participants With Local Reactogenicity Signs and Symptoms, Stratified by Severity [Time Frame: Measured for seven days through participant's last vaccination at Month 0,1,and 6]

Number of Participants With Systemic Reactogenicity Signs and Symptoms, Stratified by Severity [Time Frame: Measured for seven days through participant's last vaccination at Month 0,1,and 6]

Secondary Outcome(s)

Change in Magnitude of Env-specific CD4+ T Cells [Time Frame: Measured through Month 6.5]

Changes in Somatic Hypermutation in Participants With SLE Compared With Historical Controls [Time Frame: Measured through Month 6.5]

Change in Length of Antibody Binding Loops and Germline Gene Usage in Participants With SLE Compared With Historical Controls [Time Frame: Measured through Month 6.5]

Change in Response Rate of Env-specific CD4+ T Cells [Time Frame: Measured through Month 6.5]

Change in Vaccine-induced Immune Activation [Time Frame: Measured through Month 6.25]

Change in NAb Responses to Viruses With Altered Glycosylation, Indicative of bnAb Precursors [Time Frame: Measured through Month 6.5]

Change in Response Rate of HIV-1-Specific IgG Binding Antibodies [Time Frame: Measured through Month 6.5]

Change in Specificity of Antibody Responses [Time Frame: Measured through Month 6.5]

Change in Polyfunctionality of Env-specific CD4+ T Cells [Time Frame: Measured through Month 6.5]

Change in Magnitude of HIV-1-Specific IgG Binding Antibodies [Time Frame: Measured through Month 6.5]

Secondary ID(s)

38162

HVTN 121

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/12/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03618056