primary objectives

Antibodies are one of the natural ways that our bodies fight infection. Giving people antibodies to prevent infection has been an accepted medical practice for more than 100 years. For example, doctors give people antibodies to prevent infections like hepatitis A or B and chicken pox. Some antibodies that are used for preventing infections are made in laboratories. Manufactured antibodies have been used to prevent a dangerous respiratory infection in infants called RSV, and to treat diseases such as COVID-19, rheumatoid arthritis and breast cancer.

The study HVTN 140/HPTN 101 tests three antibodies against HIV. The antibodies are called PGDM1400LS, PGT121.414.LS and VRC07-523LS. Since antibodies are part of how the body naturally protects against infections, these antibodies cannot cause HIV.

The study antibodies were developed from antibodies discovered in the blood of people who were living with HIV. Some antibodies made by people living with HIV can block (neutralize) many different strains of HIV. These are called broadly neutralizing antibodies, or bnAbs. These antibodies attack HIV by attaching to key spots on the surface of the virus and blocking it from infecting human cells. The three study antibodies attach to different spots on HIV’s surface. Some of these natural bnAbs have been copied and made in a lab to create the study antibodies. The study antibodies have been shown to block many different global HIV strains in laboratory tests.

Because no single bnAb discovered so far can block all global strains of HIV, scientists think that using combinations of different bnAbs may block more HIV strains. They think that using combinations may be more effective to prevent HIV.

In this study, the PGDM1400LS study antibody will be tested by itself at different doses and in combination with the PGT121.414.LS and VRC07-523LS antibodies. The study antibodies will be given by intravenous (IV) (into the vein) or subcutaneous (SC) (under the skin) infusion.

The main goals of this study are to see if the study antibodies are safe to give to people, and whether people are able to take the antibodies without becoming too uncomfortable.

Other questions we are trying to answer with this study are:

·         Is the new PGDM1400LS study antibody safe to give to people at different doses?

·         Are the 3 study antibodies safe to give to people together at different doses?

·         How much of the study antibodies remain in the body as time passes?

·         How do people’s immune systems respond to the study antibodies? (Your immune system protects you from disease.)

·         Does the method of giving the antibodies (IV or SC infusion) change the body’s response?

This study is expected to take about 14 months. Kericho site is planning to enroll up to 30 participants.

Globally in 2017, more than 35 million people were living with HIV, and 1.8 million people were newly infected with the virus (4). There were 940,000 deaths attributable to HIV infection. According to Kenya Ministry of Health report of 2017, there were approximately 52,800 new infections across all ages; 44,800 among adults aged 15+ years and 8,000 among children. The recent discovery of multiple potent and broadly neutralizing antibodies (bnAbs) against HIV has led to the re-emergence of the concept that passive administration of antibodies may be useful for prevention of HIV. A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, and pharmacokinetics of PGDM1400LS alone and in combination with VRC07-523LS and PGT121.414.LS in healthy, HIV-uninfected adult participants. Primary objective of the study is to evaluate the safety and tolerability of PGDM1400LS when administered via intravenous (IV) or subcutaneous (SC) routes (Part A) and of PGDM1400LS + VRC07-523LS + PGT121.414.LS when administered in sequence IV or SC (Part B), evaluate the serum concentrations and pharmacokinetics of PGDM1400LS after a single administration (Part A) and of PGDM1400LS + VRC07-523LS + PGT121.414.LS after each three-mAb administration (Part B), and to evaluate the individual mAb-specific serum neutralizing activity after single product administration of PGDM1400LS (Part A) and after each three-mAb administration of PGDM1400LS, VRC07-523LS and PGT121.414.LS (Part B). The study products are; PGDM1400LS: a human mAb that targets the HIV-1 V2 glycan, PGT121. 414.LS is a human mAb that targets the HIV-1 V3 glycan centered on N332 and VRC-HIVMAB075-00-AB (VRC07-523LS) is a human mAb that targets the HIV-1 CD4 binding site. About 95 healthy, HIV-1–uninfected volunteers aged 18 through 50 years with a study duration per participant being 6 months in Part A and 10 months in Part B. Kericho site is looking at screening 60 participants to enroll up to 30 participants. The study’s estimated total duration is 14 months (includes enrollment, planned safety holds, and follow-up).