Evaluating the Safety and Pharmacokinetics of VRC07-523LS in the Sera and Mucosae of Healthy, HIV-Uninfected Adult Participants

NCT03735849 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 12838523
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety and pharmacokinetics of a human monoclonal antibody (VRC07-523LS) in the sera and mucosae of healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (14)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms

  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 through 3 days after each infusion at weeks 0, 16 and 32

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms

  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 through 3 days after each infusion at weeks 0, 16 and 32

• Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT) in U/L

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, visit 4(day 14), 6 (day 126) and 8 (day 238)

• Chemistry and Hematology Laboratory Measures- Hemoglobin and Creatinine (g/dl)

  For each local laboratory measure-Hemoglobin and Creatinine (g/dl), summary statistics were presented by treatment group and time point for the overall population.

  Measured during screening, Day 14, 126, 238

• Chemistry and Hematology Laboratory Measures- Lymphocyte Count, Neutrophil Count, Platelets, White Blood Cells (WBC)

  For each local laboratory measure lymphocyte count, neutrophil count, platelets, white blood cells (WBC) in 1000/ cubic mm summary statistics were presented by treatment group and time point

  Measured during screening, Day 14, 126, 238

• Chemistry and Hematology Laboratory Measures

  Counts of lab grade \>1 for ALT, creatine, hemoglobin, lymphocyte count, neutrophil, platelets, white blood cells

  Measured during screening, Day 14, 126, 238

• Number of Participants Reporting Adverse Events (AEs)

  Participants Max severity reported per participant over visit.

  Enrollment through week 48

• Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation

  The number (percentage) of participants with early discontinuation of vaccinations and reason for discontinuation was summarized by arm

  Enrollment through last scheduled dose at week 32

• Unnormalized Levels of VRC07-523LS in Genital and Rectal Secretions, as Well as Cervical, Vaginal, and Rectal Tissues at the Collection Timepoints

  Pharmacokinetic - Single Molecule Counting (PK-SMC) assay were used to measure passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant mucosa (secretions and biopsies) using 5C9 anti-idiotype antibody (anti-ID). Outcome measure is the concentration of VRC07-523LS.

  Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48) in secretion samples (semen, cervicovaginal, and rectal) and at Visits 2, 4, 8, 9 (Weeks -2, 2, 34, 48) in biopsy samples (rectal, cervical, and vaginal).

• IgG-normalized Levels of VRC07-523LS in Genital and Rectal Secretions, as Well as Cervical, Vaginal, and Rectal Tissues at the Collection Timepoints

  Pharmacokinetic - Single Molecule Counting (PK-SMC) assay were used to measure passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant mucosa (secretions and biopsies) using 5C9 anti-idiotype antibody (anti-ID). Outcome measure is the IgG-normalized VRC07-523LS levels performed by dividing VRC07-523LS levels (pg/mL) by the total IgG (ng/mL).

  Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48) in secretion samples (semen, cervicovaginal, and rectal) and at Visits 2, 4, 8, 9 (Weeks -2, 2, 34, 48) in biopsy samples (rectal, cervical, and vaginal).

• Protein-normalized Levels of VRC07-523LS in Genital and Rectal Secretions, as Well as Cervical, Vaginal, and Rectal Tissues at the Collection Timepoints

  Pharmacokinetic - Single Molecule Counting (PK-SMC) assay were used to measure passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant mucosa (secretions and biopsies) using 5C9 anti-idiotype antibody (anti-ID). Outcome measure is the protein-normalized VRC07-523LS levels performed by dividing VRC07-523LS levels (pg/mL) by the total protein (ng/mL).

  Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48) in secretion samples (semen, cervicovaginal, and rectal) and at Visits 2, 4, 8, 9 (Weeks -2, 2, 34, 48) in biopsy samples (rectal, cervical, and vaginal).

• Unnormalized Levels of VRC07-523LS in Serum Out to Week 48, 16 Weeks After the Last Product Administration

  Pharmacokinetic - Binding Antibody Multiplex Assay (PK-BAMA) was used to measure levels of passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant sera using 5C9 anti-IDiotype antibody (anti-ID). Outcome measure is the concentration of VRC07-523LS.

  Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48).

• IgG-normalized Levels of VRC07-523LS in Serum Out to Week 48, 16 Weeks After the Last Product Administration

  Pharmacokinetic - Binding Antibody Multiplex Assay (PK-BAMA) was used to measure levels of passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant sera using 5C9 anti-IDiotype antibody (anti-ID). Outcome measure is the IgG-normalized VRC07-523LS levels performed by dividing VRC07-523LS levels (pg/mL) by the average reference values for total IgG concentrations in serum in the USA (11,650,000 ng/mL).

  Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48).

• Protein-normalized Levels of VRC07-523LS in Serum Out to Week 48, 16 Weeks After the Last Product Administration

  Pharmacokinetic - Binding Antibody Multiplex Assay (PK-BAMA) was used to measure levels of passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant sera using 5C9 anti-idiotype antibody (anti-ID). Outcome measure is the protein-normalized VRC07-523LS levels performed by dividing VRC07-523LS levels (pg/mL) by the total protein (ng/mL).

  Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48).

Secondary Outcomes (1)

• Serum Concentration of ADA in Each Group Measured at Multiple Timepoints From Baseline Through the Final Study Visit

  Measured at Visits 2, 3, 5, 7, and 9 (Weeks -2, 0, 16, 32, 48). However, Tier 3 ADA titers are only assessed and reported at Visits 2 and 3 (Weeks -2 and 0) for the subset of participants who tested positive for ADA Tiers 1 and 2.

Study Arms (3)

Pre-treatment

NO INTERVENTION

Biopsy collected but was not randomized to any treatment group

Group 1: VRC07-523LS

EXPERIMENTAL

Participants will receive 10 mg/kg of VRC07-523LS at Weeks 0, 16, and 32.

Biological: VRC07-523LS

Group 2: VRC07-523LS

EXPERIMENTAL

Participants will receive 30 mg/kg of VRC07-523LS at Weeks 0, 16, and 32.

Biological: VRC07-523LS

Interventions

VRC07-523LS BIOLOGICAL

Administered by intravenous (IV) infusion

Also known as: VRC-HIVMAB075-00-AB

Group 1: VRC07-523LS; Group 2: VRC07-523LS

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit
• 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 the study protocol for US Low risk guidelines.
• 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 feminizing 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 (WBC) count equal to 2,500 to 12,000 cells/mm\^3
• WBC differential either within institutional normal range or with site physician approval

You may not qualify if:

• General
• Weight greater than 115 kg
• Blood products received within 120 days before first study product administration unless eligibility for earlier enrollment is determined by the HVTN 128 PSRT
• Investigational research agents received within 30 days before first study product administration
• 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 study
• Pregnant or breastfeeding
• 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 128 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of humanized or human monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 128 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies against HIV
• Immune System
• Serious adverse reactions to VRC07-523LS formulation components (sucrose, histidine, and sorbitol; see study protocol for more information), including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
• Immunoglobulin received within 90 days before first infusion unless eligibility for earlier enrollment is determined by the HVTN 128 PSRT
• Autoimmune disease (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate Solicited and Unsolicited AE assessments)
• Immunodeficiency

Sponsors & Collaborators

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

Study Sites (2)

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115-6110, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

MeSH Terms

Conditions

HIV Infections

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

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Stephen Walsh

  Brigham and Women's Hospital

  STUDY CHAIR

• Maria Lemos

  Fred Hutch

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 8, 2018
• Study Start: January 18, 2019
• Primary Completion: December 21, 2020
• Study Completion: December 21, 2020
• Last Updated: June 5, 2025
• Results First Posted: March 7, 2022

Record last verified: 2025-05

Locations

US (2)