A5377: Tri-specific Antibody

The first study of a broadly neutralizing antibody called SAR441236 in humans, will determine if an infusion is safe and tolerable and will measure the amount of SAR441236 in the blood over time. It will also evaluate whether SAR441236 can reduce the amount of HIV in a person’s blood.

Antibodies that develop naturally against HIV recognize and attach to one part of the virus so that the body’s immune system can try to attack it. Antibodies are usually made by a person’s own immune system, but they can also be manufactured as a drug. SAR441236 has been manufactured to attach to three parts of the HIV virus at the same time, and to neutralize (or block) the ability of the virus to infect more cells.

A5377 is the first study of SAR441236 in humans. This study will enroll two groups of people with HIV: Arm A—people who are on an anti-HIV regimen with an undetectable HIV viral load will receive either SAR441236 or placebo in four increasing dosing groups; and Arm B—people who have never received anti-HIV medications will receive SAR441236 in four increasing dosing groups.

This study will determine if one infusion of SAR441236 is safe and tolerable, and will measure the amount of SAR441236 in the blood over time. The study will see if SAR441236 can reduce the amount of HIV in a person’s blood. Increasing dose levels and multiple infusions will be studied.

People with HIV who:

• Are 18 to 70 years of age
• Have no active Hepatitis B or C infection

Arm A:

• Have taken anti-HIV medications for at least 12 months
• Have “undetectable” HIV viral load for at least 12 months
• Have a CD4 count greater than 200

Arm B:

• Have never taken anti-HIV medications (including pre-exposure prophylaxis [PrEP])
• Have an HIV viral load of 5000 to 100,000 copies
• Have a CD4 count greater than 350
• Are willing and able to start anti-HIV medications

Arm A: Participants will be assigned to one of the following dosing groups, and will be randomly assigned (by chance) to receive one infusion of either:

• 1 mg/kg SAR441236 or placebo
• 3 mg/kg SAR441236 or placebo
• 10 mg/kg SAR441236 or placebo
• 30 mg/kg SAR441236 or placebo (four infusions, one every 12 weeks)

Participants will continue to take their anti-HIV medications throughout the study.

Arm B: Participants will be enrolled in one of the following dosing groups and will receive one infusion of:

• 1 mg/kg SAR441236
• 3 mg/kg SAR441236
• 10 mg/kg SAR441236
• 30 mg/kg SAR441236

0.3 mg/kg SAR441236—this dosing group might or might not be included in the study

Participants will start taking anti-HIV medications by Day 28 of the study.

SAR441236 or placebo will be given as an infusion in the arm.

On the day of the infusion, blood will be collected over 24 hours, so participants may need to stay in the clinic overnight. Participants will have blood collected for safety monitoring. When and if it is determined that a lower dose is safe, the next higher dosing group will be opened for enrollment.

SAR441236 and placebo will be provided through the study. Anti-HIV medications will not be supplied through this study.

Most participants will be followed on study for 24 weeks after their infusion. Participants who receive multiple infusions will be followed for a total of 72 weeks.