A Study of Safety and Drug Levels of ePGT121v1-LS, PGDM1400LS, and VRC07-523LS in Adult Participants Without HIV-1

NCT07390955 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: HVTN 141/HPTN 10538950
• Study Type: interventional
• Target: 83
• Locations: 3 countries
• Sites: 11

Brief Summary

This study is testing a lab-made antibody called ePGT121v1-LS that targets a specific part of HIV. Researchers will give it by vein (IV) and under the skin (SC), both on its own and together with two other antibodies, VRC07-523LS and PGDM1400LS, which target different parts of the virus. They will assess safety and side effects, determine the right dose, study how the body processes the drug (pharmacokinetics or PK), and measure how well it neutralizes HIV in the blood (serum neutralizing activity). The expectation is that ePGT121v1-LS, whether given alone or with PGDM1400LS and VRC07-523LS, by IV or SC, will be safe in generally healthy adults and that the antibodies will not interfere with each other when used together. Approximately 83 volunteers in overall good health and without HIV-1 will be enrolled into two parts (A and B). Part A has six groups. In Groups 1-3, participants will get ePGT121v1-LS given by IV at one of three dose levels: 5 mg/kg, 20 mg/kg, or 40 mg/kg. In Groups 4-6, participants will receive three antibodies-first ePGT121v1-LS, then PGDM1400LS and VRC07-523LS-given by IV at two separate visits that are 24 weeks apart. The total study duration for participants in Part A is 48 weeks of scheduled clinic visits. Part B has two groups. In Group 7, people will get ePGT121v1-LS as SC shots at two visits 12 weeks apart. Each visit will give a total of 375 mg, split into three injections of 125 mg each. In Group 8, people will also have two visits 12 weeks apart and will receive three antibodies as SC shots in this order: first ePGT121v1-LS (125 mg), then PGDM1400LS (100 mg), and then VRC07-523LS (100 mg). The total study duration for participants in Part B is 24 weeks of scheduled clinic visits.

Conditions

HIV

Outcome Measures

Primary Outcomes (76)

• Part A: Number of participants with solicited local Adverse Events (AEs)

  Baseline through Week 48

• Part B: Number of participants with solicited local Adverse Events (AEs)

  Baseline through Week 24

• Part A: Percentage of participants with solicited local Adverse Events (AEs)

  Baseline through Week 48

• Part B: Percentage of participants with solicited local Adverse Events (AEs)

  Baseline through Week 24

• Part A: Number of participants with solicited systemic AEs

  Baseline through Week 48

• Part B: Number of participants with solicited systemic AEs

  Baseline through Week 24

• Part A: Percentage of participants with solicited systemic AEs

  Baseline through Week 48

• Part B: Percentage of participants with solicited systemic AEs

  Baseline through Week 24

• Part A: Percentage of participants with safety laboratory abnormalities meeting grade 1 AE criteria or above

  Baseline through Week 48

• Part B: Percentage of participants with safety laboratory abnormalities meeting grade 1 AE criteria or above

  Baseline through Week 24

• Part A: Number of participants with unsolicited AEs

  Baseline through Week 48

• Part B: Number of participants with unsolicited AEs

  Baseline through Week 24

• Part A: Percentage of participants with unsolicited AEs

  Baseline through Week 48

• Part B: Percentage of participants with unsolicited AEs

  Baseline through Week 24

• Part A: Number of participants with Serious Adverse Events (SAEs)

  Baseline through Week 48

• Part B: Number of participants with Serious Adverse Events (SAEs)

  Baseline through Week 24

• Part A: Percentage of participants with Serious Adverse Events (SAEs)

  Baseline through Week 48

• Part B: Percentage of participants with Serious Adverse Events (SAEs)

  Baseline through Week 24

• Part A: Number of participants who discontinue study product administration

  Baseline through Week 48

• Part B: Number of participants who discontinue study product administration

  Baseline through Week 24

• Part A: Percentage of participants who discontinue study product administration

  Baseline through Week 48

• Part B: Percentage of participants who discontinue study product administration

  Baseline through Week 24

• Part A: Number of participants who terminate the study early

  Baseline through Week 48

• Part B: Number of participants who terminate the study early

  Baseline through Week 24

• Part A: Percentage of participants who terminate the study early

  Baseline through Week 48

• Part B: Percentage of participants who terminate the study early

  Baseline through Week 24

• Part A: Serum Concentration of ePGT121v1-LS

  Measured by anti-idiotype binding antibody multiplex assay

  Baseline through Week 48

• Part B: Serum Concentration of ePGT121v1-LS

  Measured by anti-idiotype binding antibody multiplex assay

  Baseline through Week 24

• Part A: Serum Concentration of PGDM1400LS

  Measured by anti-idiotype binding antibody multiplex assay

  Baseline through Week 48

• Part B: Serum Concentration of PGDM1400LS

  Measured by anti-idiotype binding antibody multiplex assay

  Baseline through Week 24

• Part A: Serum Concentration of VRC07-523LS

  Measured by anti-idiotype binding antibody multiplex assay

  Baseline through Week 48

• Part B: Serum Concentration of VRC07-523LS

  Measured by anti-idiotype binding antibody multiplex assay

  Baseline through Week 24

• Part A: Area Under the Concentration-Time Curve (AUC) of ePGT121v1-LS

  Baseline through Week 48

• Part B: AUC of ePGT121v1-LS

  Baseline through Week 24

• Part A: AUC of PGDM1400LS

  Baseline through Week 48

• Part B: AUC of PGDM1400LS

  Baseline through Week 24

• Part A: AUC of VRC07-523LS

  Baseline through Week 48

• Part B: AUC of VRC07-523LS

  Baseline through Week 24

• Part A: Maximum Observed Concentration (Cmax) of ePGT121v1-LS

  Baseline through Week 48

• Part B: Cmax of ePGT121v1-LS

  Baseline through Week 24

• Part A: Cmax of PGDM1400LS

  Baseline through Week 48

• Part B: Cmax of PGDM1400LS

  Baseline through Week 24

• Part A: Cmax of VRC07-523LS

  Baseline through Week 48

• Part B: Cmax of VRC07-523LS

  Baseline through Week 24

• Part A: Time to Maximum Concentration (Tmax) of ePGT121v1-LS

  Baseline through Week 48

• Part B: Tmax of ePGT121v1-LS

  Baseline through Week 24

• Part A: Tmax of PGDM1400LS

  Baseline through Week 48

• Part B: Tmax of PGDM1400LS

  Baseline through Week 24

• Part A: Tmax of VRC07-523LS

  Baseline through Week 48

• Part B: Tmax of VRC07-523LS

  Baseline through Week 24

• Part A: Clearance (CL) of ePGT121v1-LS

  Baseline through Week 48

• Part B: CL of ePGT121v1-LS

  Baseline through Week 24

• Part A: CL of PGDM1400LS

  Baseline through Week 48

• Part B: CL of PGDM1400LS

  Baseline through Week 24

• Part A: CL of VRC07-523LS

  Baseline through Week 48

• Part B: CL of VRC07-523LS

  Baseline through Week 24

• Part A: Volume of Distribution (Vd) of ePGT121v1-LS

  Baseline through Week 48

• Part B: Vd of ePGT121v1-LS

  Baseline through Week 24

• Part A: Vd of PGDM1400LS

  Baseline through Week 48

• Part B: Vd of PGDM1400LS

  Baseline through Week 24

• Part A: Vd of VRC07-523LS

  Baseline through Week 48

• Part B: Vd of VRC07-523LS

  Baseline through Week 24

• Part A: Terminal Elimination Rate Constant (λz) of ePGT121v1-LS

  Baseline through Week 48

• Part B: λz of ePGT121v1-LS

  Baseline through Week 24

• Part A: λz of PGDM1400LS

  Baseline through Week 48

• Part B: λz of PGDM1400LS

  Baseline through Week 24

• Part A: λz of VRC07-523LS

  Baseline through Week 48

• Part B: λz of VRC07-523LS

  Baseline through Week 24

• Part A: Terminal Half-life (T1/2) of ePGT121v1-LS

  Baseline through Week 48

• Part B: T1/2 of ePGT121v1-LS

  Baseline through Week 24

• Part A: T1/2 of PGDM1400LS

  Baseline through Week 48

• Part B: T1/2 of PGDM1400LS

  Baseline through Week 24

• Part A: T1/2 of VRC07-523LS

  Baseline through Week 48

• Part B: T1/2 of VRC07-523LS

  Baseline through Week 24

• Part A: Area Under the Magnitude-Breadth Curve (AUC-MB)

  The AUC-MB to a global panel of pseudoviruses (78) will be computed for each evaluable participant

  Baseline through Week 48

• Part B: AUC-MB

  The AUC-MB to a global panel of pseudoviruses (78) will be computed for each evaluable participant

  Baseline through Week 24

Secondary Outcomes (8)

• Serum Concentration of ePGT121v1-LS

  Baseline through Week 48

• Serum Concentration of PGDM1400LS

  Baseline through Week 48

• Serum Concentration of VRC07-523LS

  Baseline through Week 48

• Correlation Between Serum/Plasma Concentration and Serum Neutralization Titer (ID50) for Each Virus

  Baseline through Week 48

• Correlation Between Serum/Plasma Concentration and Serum Neutralization Titer (ID80) for Each Virus

  Baseline through Week 48

Study Arms (8)

Part A: Group 1

EXPERIMENTAL

ePGT121v1-LS 5 mg/kg to be administered via intravenous (IV) infusion at Week 0 and Week 24

Biological: ePGT121v1-LS (IV)

Part A: Group 2

EXPERIMENTAL

ePGT121v1-LS 20 mg/kg to be administered via IV infusion at Week 0 and Week 24

Biological: ePGT121v1-LS (IV)

Part A: Group 3

EXPERIMENTAL

ePGT121v1-LS 40 mg/kg to be administered via IV infusion at Week 0 and Week 24

Biological: ePGT121v1-LS (IV)

Part A: Group 4

EXPERIMENTAL

ePGT121v1-LS 5 mg/kg + PGDM1400LS 5 mg/kg + VRC07-523LS 5 mg/kg to be administered via IV infusion sequentially in this order at Week 0 and Week 24

Biological: ePGT121v1-LS (IV); Biological: PGDM1400LS (IV); Biological: VRC07-523LS (IV)

Part A: Group 5

EXPERIMENTAL

ePGT121v1-LS 20 mg/kg + PGDM1400LS 20 mg/kg + VRC07-523LS 20 mg/kg to be administered via IV infusion sequentially in this order at Week 0 and Week 24

Biological: ePGT121v1-LS (IV); Biological: PGDM1400LS (IV); Biological: VRC07-523LS (IV)

Part A: Group 6

EXPERIMENTAL

ePGT121v1-LS 40 mg/kg + PGDM1400LS 40 mg/kg + VRC07-523LS 40 mg/kg to be administered via IV infusion sequentially in this order at Week 0 and Week 24

Biological: ePGT121v1-LS (IV); Biological: PGDM1400LS (IV); Biological: VRC07-523LS (IV)

Part B: Group 7

EXPERIMENTAL

ePGT121v1-LS 375 mg (3 injections of 125 mg each) to be administered via subcutaneous (SC) injection at Week 0 and Week 12

Biological: ePGT121v1-LS (SC)

Part B: Group 8

EXPERIMENTAL

ePGT121v1-LS 125 mg + PGDM1400LS 100 mg + VRC07-523LS 100 mg to be administered via SC injection sequentially in this order at Week 0 and Week 12

Biological: ePGT121v1-LS (SC); Biological: PGDM1400LS (SC); Biological: VRC07-523LS (SC)

Interventions

ePGT121v1-LS (IV) BIOLOGICAL

Intravenous infusion (IV)

Part A: Group 1; Part A: Group 2; Part A: Group 3; Part A: Group 4; Part A: Group 5; Part A: Group 6

PGDM1400LS (SC) BIOLOGICAL

SC injection

Part B: Group 8

VRC07-523LS (IV) BIOLOGICAL

IV infusion

Part A: Group 4; Part A: Group 5; Part A: Group 6

VRC07-523LS (SC) BIOLOGICAL

SC injection

Part B: Group 8

ePGT121v1-LS (SC) BIOLOGICAL

Subcutaneous (SC) injection

Part B: Group 7; Part B: Group 8

PGDM1400LS (IV) BIOLOGICAL

IV infusion

Part A: Group 4; Part A: Group 5; Part A: Group 6

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 55 years.
• Can visit a participating clinic and is willing to stay in the study for its full duration.
• Understands the study and is able and willing to give informed consent.
• Agrees not to join another experimental study until the final required clinic visit.
• In good overall health based on medical history, physical exam, and screening lab tests.
• Willing to receive HIV test results.
• Willing to discuss personal risk of getting HIV and to have HIV prevention counseling.
• Judged by clinic staff to have a low risk of getting HIV and agrees to avoid higher risk behaviors through the last clinic visit.
• Hemoglobin levels:
• Women: at least 11.0 g/dL
• Men: at least 13.0 g/dL
• White blood cell count between 2,500 and 12,000 cells/mm³.
• White blood cell differential is normal or acceptable to clinic staff.
• Platelet count between 125,000 and 550,000 cells/mm³.
• ALT (liver enzyme) less than 1.25 times the lab's upper limit of normal.

You may not qualify if:

• Received blood products within 120 days before the first study dose (unless the safety review team approves earlier enrollment).
• Took any experimental (investigational) research drug within 30 days before the first study dose.
• Weighs less than 35 kg or more than 115 kg.
• Plans to join another study using an experimental product, or any study that requires non Network HIV antibody testing, during this study.
• Pregnant or breastfeeding.
• Previously received an HIV vaccine in a vaccine trial. If a potential participant received placebo/control only, eligibility will be decided case by case by the safety review team.
• Received any non HIV vaccine within 14 days before enrollment or plan to get one within 14 days after enrollment. Exception: ACAM2000 smallpox vaccine within 28 days before enrollment (or scab still present if earlier) or planned within 14 days after enrollment.
• Received humanized or human monoclonal antibodies (mAbs), whether approved or experimental.
• Previously received monoclonal antibodies that target HIV.
• Receiving allergy shots within 30 days before the first study dose or scheduled within 14 days after the first dose.
• Took immune suppressing medicines within 30 days before the first study dose. Not excluded: nasal steroid sprays; inhaled steroids (see asthma item); topical steroids for mild skin conditions; or one short course of oral/IV prednisone (less than 20 mg/day for under 14 days) finished at least 7 days before the first infusion/injection.
• History of serious reactions to components of the study products, including anaphylaxis or symptoms like hives, trouble breathing, swelling (angioedema), or abdominal pain.
• Received immunoglobulin within 60 days before the first study dose (separate from mAbs listed above).
• Autoimmune disease that is not mild, stable, and uncomplicated. Mild, stable cases not needing immune suppressing drugs may be allowed if the investigator judges low risk.
• Immunodeficiency.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institutes of Health (NIH): collaborator
• Department of Health and Human Services: collaborator

Study Sites (11)

Alabama CRS (Site ID: 31788)

Birmingham, Alabama, 35222, United States

RECRUITING

Bridge HIV CRS (Site ID: 30305)

San Francisco, California, 94102, United States

RECRUITING

The Ponce de Leon Center CRS (Site ID: 5802)

Atlanta, Georgia, 30308, United States

NOT YET RECRUITING

Brigham and Women's Hospital Vaccine CRS (BWH VCRS) (Site ID: 30007)

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Penn Prevention CRS (Site ID: 30310)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Vanderbilt Vaccine (VV) CRS (Site ID: 30352)

Nashville, Tennessee, 37232, United States

RECRUITING

Houston Advancing Research Team CRS (Site ID: 31473)

Houston, Texas, 77030, United States

NOT YET RECRUITING

Via Libre CRS (Site ID: 31909)

Lima Cercado, Lima region, 15001, Peru

NOT YET RECRUITING

Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC) (Site ID: 31970)

Bellavista, Provincia Constitucional del Callao, 07006, Peru

NOT YET RECRUITING

Seke South CRS (Site ID: 30294)

Harare, Zimbabwe

NOT YET RECRUITING

Spilhaus CRS (Site ID: 30314)

Harare, Zimbabwe

NOT YET RECRUITING

Study Design

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

Study Record Dates

• First Submitted: December 22, 2025
• First Posted: February 5, 2026
• Study Start: March 19, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2027
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); PE (2); ZI (2)