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

NCT03618056 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 12138162
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infections; Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (7)

• 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 through Month 6.5

• 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 through Month 6.5

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

  Assessed by TZM-bl assay

  Measured through Month 6.5

• 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 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

  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 for seven days through participant's last vaccination at Month 0,1,and 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 through Month 12

• 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 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)

• Changes in Somatic Hypermutation in Participants With SLE Compared With Historical Controls

  Measured through Month 6.5

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

  Measured through Month 6.5

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

  Measured through Month 6.5

• Change in Vaccine-induced Immune Activation

  Measured through Month 6.25

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

  Measured through Month 6.5

Study Arms (1)

AIDSVAX® B/E

EXPERIMENTAL

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

Biological: AIDSVAX® B/E

Interventions

AIDSVAX® B/E BIOLOGICAL

Administered by intramuscular injection

AIDSVAX® B/E

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)
• Hemogram/Complete blood count (CBC)

You may not qualify if:

• General
• Blood products received within 120 days before first vaccination
• 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 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Duke Human Vaccine Institute CRS

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

HIV Infections; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases

Results Point of Contact

• Title: Jessica Andriesen
• Organization: Fred Hutchinson Cancer Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• M. Anthony Moody

  Duke University

  STUDY CHAIR

• Paul Goepfert

  University of Alabama at Birmingham

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 7, 2018
• Study Start: December 19, 2018
• Primary Completion: July 17, 2020
• Study Completion: July 17, 2020
• Last Updated: February 7, 2022
• Results First Posted: December 29, 2021

Record last verified: 2022-01

Locations

US (1)