PGT121.414.LS + VRC07-523LS for HIV

Not yet recruiting at 21 trial locations

Overseen By Emily Brown

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Disqualifiers: Positive HIV NAT, Investigational products, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two powerful antibodies, PGT121.414.LS and VRC07-523LS, to determine their safety and behavior in newborns exposed to HIV-1. The goal is to assess whether these antibodies can protect infants from HIV soon after birth. Eligible participants are babies born to parents with confirmed HIV-1 infection, and they must be less than 72 hours old. The trial includes different treatment plans for breastfed and formula-fed infants. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for this trial?

The trial information does not specify whether participants need to stop taking their current medications. It is best to discuss this with the study team or your healthcare provider.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies found PGT121.414.LS to be safe and well-tolerated in people both with and without HIV. Research showed no major side effects when used alone or with other treatments. Similarly, tests of VRC07-523LS in different doses and methods also found it to be safe and well-tolerated. These findings suggest that both treatments are generally safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments PGT121.414.LS and VRC07-523LS for HIV because they represent a novel approach to preventing the virus. Unlike traditional antiretroviral therapies that require daily dosing and focus on suppressing the virus in the body, these treatments are monoclonal antibodies designed to block HIV infection right from the start. By targeting specific proteins on the virus, they aim to prevent it from entering human cells. This could offer a powerful new tool for protecting newborns from HIV transmission, especially since they are administered as injections at birth and potentially at 12 weeks, which is a significant shift from the daily medication regimen of other treatments.

What evidence suggests that this trial's treatments could be effective for HIV?

Research has shown that the monoclonal antibody PGT121.414.LS can neutralize 64% of over 600 hard-to-treat HIV-1 strains, indicating its potential effectiveness against many types of HIV. In this trial, some participants will receive PGT121.414.LS alone, while others will receive a combination of PGT121.414.LS and VRC07-523LS. VRC07-523LS is a promising long-lasting antibody for preventing HIV, known for its safety and tolerance. It has also proven effective when combined with other antibodies to control HIV. Both treatments could help prevent HIV in newborns exposed to the virus. These findings offer hope that they could be strong tools in the fight against HIV. ^{1 4 5 6 7}

Who Is on the Research Team?

Coleen Cunningham

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

This trial is for infants exposed to HIV-1, under 72 hours old, generally healthy, with a birth weight of at least 2 kg and born after at least 36 weeks of gestation. Infants must be at increased risk of HIV acquisition. Those breastfeeding or not are included in separate strata. Parents must consent for participation and have confirmed HIV-1 infection.

Inclusion Criteria

For Cohorts 1 and 2, Strata BF: At entry, infant is breastfeeding or the birthing parent has indicated an intention to initiate breastfeeding

I plan to breastfeed, according to my own decision.

My newborn is less than 3 days old and can start the study within 3 days after birth.

Exclusion Criteria

Birthing parent has received any investigational product during this pregnancy

Birthing parent or infant has any condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

At entry, infant with a documented positive HIV Nucleic Acid Test (NAT) result

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Initial subcutaneous doses of PGT121.414.LS and VRC07-523LS administered at birth, with a second dose at Week 12 if still breastfeeding

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and pharmacokinetics through Week 24

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PGT121.414.LS
• VRC07-523LS

Trial Overview The study tests the safety and how the body processes two anti-HIV antibodies (PGT121.414.LS alone and combined with VRC07-523LS) administered soon after birth to infants exposed to HIV-1.

How Is the Trial Designed?

Group I: Cohort 2 Stratum FF Experimental Treatment 2 Interventions

Single SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight.

Group II: Cohort 2 Stratum BF Experimental Treatment 2 Interventions

Initial SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight. Second SC doses of 100 mg of PGT121.414.LS and 100 mg VRC07-523LS at Week 12, if still breastfeeding. Dosing at Week 12 is not based on weight.

Group III: Cohort 1 Stratum Formula Fed (FF) Experimental Treatment 1 Intervention

Single subcutaneous (SC) dose of PGT121.414.LS at birth, based on weight.

Group IV: Cohort 1 Stratum Breastfed (BF) Experimental Treatment 1 Intervention

Initial SC dose of PGT121.414.LS at birth, based on weight. Second SC dose of 100 mg PGT121.414.LS at Week 12, if still breastfeeding. Dosing at Week 12 is not based on weight.

PGT121.414.LS is already approved in United States for the following indications:

Approved in United States as PGT121.414.LS for:

• HIV-1 infection

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

National Institute of Allergy and Infectious Diseases Vaccine Research Center

Collaborator

Trials

1

Recruited

50+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

National Institute of Allergy and Infectious Diseases Vaccine Research Center (NIAID VRC)

Collaborator

Trials

1

Recruited

50+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8516645/

Safety, pharmacokinetics and antiviral activity of PGT121, a ... was able to neutralize 64% of 634 diverse tier 2 (for example, more difficult to neutralize) HIV-1 strains tested and recorded in the Los Alamos ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352301824002479

Safety, tolerability, pharmacokinetics, and neutralisation ... The aim of this trial was to test the PGT121.414.LS and VRC07-523LS mAbs for safety and pharmacokinetics in adults.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04212091

Study Details | NCT04212091 | Evaluating the Safety, ... This study will evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the monoclonal antibody PGT121.414.LS administered alone and in ...

4. nature.com nature.com/articles/s41591-024-03247-5

Safety and antiviral effect of a triple combination of HIV-1 ... These data show that the triple-bNAb cocktail maintained virologic suppression for >28 weeks in the majority of PLWH in this trial, with viral ...

5. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/drugs/pgt121/health-professional

PGT121 Health Professional Drug Record | NIH Study Purpose: The purpose of this study is to evaluate the safety, immunogenicity, and efficacy of therapeutic HIV vaccines (Ad26.Mos4.HIV prime and MVA-BN-HIV ...

6. nature.com nature.com/articles/s41591-021-01509-0

Safety, pharmacokinetics and antiviral activity of PGT121 ... Finally, our data demonstrate that PGT121 monoclonal antibody was safe and well tolerated in both HIV-uninfected and HIV-infected ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34621054/

a randomized, placebo-controlled, phase 1 clinical trial Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo- ...