Clinical trial NCT06812494: A Study of VRC07-523LS, PGT121.414.LS, and PGDM1400LS Broadly Neutralizing Monoclonal Antibodies Given Intravenously in Adult Participants Without HIV
Official title: A Randomized, Double Blind, Controlled, Phase 2 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Neutralization of VRC07-523LS, PGT121.414.LS, and PGDM1400LS Broadly Neutralizing Monoclonal Antibodies Given Intravenously in Adult Participants Without HIV
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HIV
Keywords: HIV Prevention
bnAb
Monoclonal antibody
Intravenous
Triple combination
VRC07-523LS
PGT121.414.LS
PGDM1400LS
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Institutes of Health (NIH)
name: Department of Health and Human Services
name: Dale and Betty Bumpers Vaccine Research Center (VRC)
First posted: 2025-02-06
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: HVTN 206/HPTN 114 is a randomized, double blind, controlled, phase 2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, and neutralization of VRC07-523LS, PGT121.414.LS, and PGDM1400LS broadly neutralizing monoclonal antibodies given intravenously in adult participants without HIV.

The hypothesis of the study is that the combination of VRC07-523LS and PGT121.414.LS and PGDM1400LS antibodies when administered via the intravenous (IV) route will be safe and tolerable in adult participants without HIV.

The study aims to enroll 200 participants across multiple sites with an estimated total duration of participation of eighteen (18) months.


Eligibility criteria: Inclusion Criteria:

* Participants need to be between 18 and 65 years old.
* Participants must have access to a participating clinical research site and be willing to follow the study schedule.
* Participants should understand the study details and be willing to give informed consent.
* Participants must agree not to join any other clinical trials until they finish this study.
* Participants must be willing to receive HIV test results.
* Participants should be open to discussing HIV prevention.
* Clinic staff should assess participants as having a low risk of getting HIV, and participants must commit to avoiding high-risk behaviors during the study.
* Hemoglobin: Participant meets minimum levels depending on gender and hormone therapy status.
* White Blood Cells (WBC): Should be within the normal range or approved by a site clinician.
* Platelets: At least 100,000 cells/mm³.
* Alanine aminotransferase (ALT): Less than 5 times the upper normal limit.
* Creatinine: Less than 1.8 times the upper normal limit or less than 1.5 times your baseline level.
* Participants must test negative for HIV-1 and HIV-2.
* Participants urine protein must be negative or trace.

Reproductive Status:

* Participants of child-bearing potential need a negative pregnancy test within 72 hours before starting the study.
* Participants must agree to use effective birth control from at least 21 days before joining the study until the end of the study.
* Participants must agree not to try to become pregnant through any method during the study.

Exclusion Criteria:

* Participants cannot have had a blood transfusion within the last 120 days.
* Participants cannot have received experimental treatments within the last 30 days.
* Participants cannot weigh less than 35 kg (about 77 lbs).
* Participants cannot plan to join another clinical trial during this study.
* Participants cannot be pregnant or breastfeeding.
* Participants cannot have received an HIV vaccine in a previous trial (unless it was a placebo, subject to Protocol Safety Review Team's approval).
* Participants cannot have had any live vaccines within the last 14 days or non-live vaccines within the last 7 days.
* Participants cannot have had humanized or human monoclonal antibodies recently, except for certain HIV antibodies more than 12 months ago.
* Participants cannot have had allergy shots within the last 14 days.
* Participants cannot have taken immunosuppressive drugs within the last 30 days, with some exceptions like nasal sprays or mild skin treatments.
* Participants cannot participate if they have had serious allergic reactions to the components of the study product.
* Participants cannot have received immunoglobulin within the last 60 days.
* Participants cannot have an autoimmune disease that requires immunosuppressive treatment, unless it's mild and stable.
* Participants cannot have an immune system deficiency.
* Participants cannot have any significant medical condition or abnormal lab results that could impact their health during the study.
* Participants cannot have conditions that make repeated injections or blood draws difficult.
* Participants cannot have conditions requiring active medical treatment that could pose a risk during the study.
* Participants cannot have conditions that could be confused with reactions to the study product.
* Participants cannot have medical, social, or occupational conditions that would interfere with the study.
* Participants cannot have severe psychiatric conditions, like ongoing risk of suicide or recent history of suicide attempts.
* Participants cannot be undergoing treatment for tuberculosis.
* Participants cannot have severe asthma that requires frequent medication or emergency care.
* Participants cannot have diabetes mellitus (DM) (well-controlled Type 2 DM or an isolated history of gestational diabetes are not exclusionary).
* Participants blood pressure must be below 160/110 mmHg.
* Participants cannot have any diagnosed bleeding disorders.
* Participants cannot have active cancer but may be eligible if, in the investigator's estimation, they have a reasonable assurance of sustained cure, or are unlikely to experience recurrence of malignancy during the period of the study
* Participants cannot have had seizures or taken seizure medications in the past 3 years.
* Participants cannot have a history of severe allergic reactions like anaphylaxis, unless it has been well-controlled for at least 5 years.
* Participants cannot have acute or unstable hepatitis B or C, but stable chronic cases may be considered.

Primary outcomes:
measure: Number of participants experiencing local Adverse Events (AEs)
timeFrame: At Days 1, 4, 7, 169 and 173
measure: Percentage of participants experiencing local AEs
timeFrame: At Days 1, 4, 7, 169 and 173
measure: Number of participants experiencing systemic AEs
timeFrame: At Days 1, 4, 7, 169 and 173
measure: Percentage of participants experiencing systemic AEs
timeFrame: At Days 1, 4, 7, 169 and 173
measure: Number of participants experiencing unsolicited AEs
timeFrame: Baseline through Week 48
measure: Percentage of participants experiencing unsolicited AEs
timeFrame: Baseline through Week 48
measure: Number of participants experiencing Serious Adverse Events
timeFrame: Baseline through Week 48
measure: Number of participants who discontinue study product administration and terminate the study early
timeFrame: Baseline through Week 48
measure: Percentage of participants who discontinue study product administration and terminate the study early
timeFrame: Baseline through Week 48
measure: Change from baseline in ALT
timeFrame: Baseline, Days 1, 57, 169, 225 and 337
measure: Change from baseline in aspartate aminotransferase (AST)
timeFrame: Baseline, Days 1, 57, 169, 225 and 337
measure: Change from baseline in alkaline phosphatase (Alk Phos)
timeFrame: Baseline, Days 1, 57, 169, 225 and 337
measure: Change from baseline in creatinine
timeFrame: Baseline, Days 1, 57, 169, 225 and 337
measure: Change from baseline in Complete Blood Count (CBC)
timeFrame: Baseline, Days 1, 57, 169, 225 and 337
Secondary outcomes:
measure: Area under the curve (AUC) of VRC07-523LS, PGDM1400LS, and PGT121.414.LS
timeFrame: At Days 1, 4, 7, 29, 57, 169, 225 and 337
measure: Maximum concentration (C(max)) of VRC07-523LS, PGDM1400LS, and PGT121.414.LS
timeFrame: At Days 1, 4, 7, 29, 57, 169, 225 and 337
measure: Time to C(max) (T(max)) of VRC07-523LS, PGDM1400LS, and PGT121.414.LS
timeFrame: At Days 1, 4, 7, 29, 57, 169, 225 and 337
measure: Clearance (CL) of VRC07-523LS, PGDM1400LS, and PGT121.414.LS
timeFrame: At Days 1, 4, 7, 29, 57, 169, 225 and 337
measure: Volume of distribution (Vd) of VRC07-523LS, PGDM1400LS, and PGT121.414.LS
timeFrame: At Days 1, 4, 7, 29, 57, 169, 225 and 337
measure: Terminal elimination rate constant (λz) of VRC07-523LS, PGDM1400LS, and PGT121.414.LS
timeFrame: At Days 1, 4, 7, 29, 57, 169, 225 and 337
measure: Terminal half-life (T1/2) of VRC07-523LS, PGDM1400LS, and PGT121.414.LS
timeFrame: At Days 1, 4, 7, 29, 57, 169, 225 and 337
measure: Area under the magnitude-breadth curve (AUC-MB) of VRC07-523LS, PGDM1400LS, and PGT121.414.LS
timeFrame: At Days 1, 4, 7, 29, 57, 169, 225 and 337
measure: Presence of antidrug antibodies (ADAs) for VRC07-523LS, PGDM1400LS, and PGT121.414.LS
timeFrame: At Days 1, 169 and 337
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Bridge HIV, San Francisco Department of Public Health
state: California
city: Decatur
country: United States
facility: The Hope Clinic of the Emory Vaccine Research Center; Emory University
state: Georgia
city: Boston
country: United States
facility: Fenway Health
state: Massachusetts
city: Chapel Hill
country: United States
facility: Chapel Hill CRS
state: North Carolina
city: Rio De Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
city: Iquitos
country: Peru
facility: ACSA CRS
state: Maynas
city: Callao
country: Peru
facility: Citbm Crs
city: Lima
country: Peru
facility: Via Libre
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit (PHRU)
state: Gaunteng
city: Chatsworth
country: South Africa
facility: Chatsworth CRS
state: KwaZulu-Natal
city: Soshanguve - H
country: South Africa
facility: Setshaba Research Centre
state: Soshanguve
city: Cape Town
country: South Africa
facility: Groote Schuur HIV CRS
state: Western Cape Province
Study officials:
References: