NCT03254277

3BNC117-LS First-in-Human Phase 1 Study

A Phase 1 First-in-human Study of the Safety and Pharmacokinetics of 3BNC117-LS in HIV-infected and HIV-uninfected Individuals

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Rockefeller University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The proposed study is a phase 1 study of the mAb 3BNC117-LS administered intravenously in HIV uninfected individuals and HIV-infected individuals, and subcutaneously in HIV-uninfected individuals.The objectives of the study are to evaluate the safety, tolerability and pharmacokinetics of a single administration of 3BNC117-LS.

Detailed description

The proposed study is a Phase 1, open label, dose escalation cohort study of 3BNC117-LS administered intravenously in HIV-uninfected and HIV-1 infected participants. This study consists of two parts. In part A, study participants will be enrolled in an open label manner to receive a single intravenous infusion of 3BNC117-LS at one of three increasing dose levels (3 mg/kg, 10 mg/kg and 30 mg/kg). Participants in Part B will also receive a single administration of 3BNC117-LS, however, the product administered in Part B of the study derives from a new manufacturing lot. The manufacturing lot used in Part A had incomplete glycosylation of the 3BNC117-LS light chain, which has been corrected in the new lot. Participants in Part B will receive 3BNC117-LS intravenously at 30 mg/kg in an open label manner (HIV-uninfected and HIV-infected) or will be randomized to receive a subcutaneous injection of 3BNC117-LS or placebo in a double-blinded fashion (HIV-uninfected only). Part A has already been enrolled with 21 participants. Part B has a planned enrollment of 22 participants. Part A * Group 1A (n=3-6) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 3 mg/kg. * Group 1B (n=3-6) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg. * Group 1C (n=3-6) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg. * Group 2B (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels \< 20 copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels \< 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg. * Group 2C (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels \< 20 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels \< 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg. Part B * Group 1D (n=3) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg. * Group 2D (n=3) - HIV-infected individuals on ART with HIV-1 plasma RNA levels \< 20 copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg. * Group 1E (n=8) - HIV-uninfected individuals will be administered a single 1 mL (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio. * Group 1F (n=8) - HIV-uninfected individuals will be administered a single 2 mL (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio. Following 3BNC117-LS infusion, study participants will return for safety assessments at weeks 1, 2 and 4 following infusion, then bi-monthly or monthly until the end of study follow up. Serum samples for PK (pharmacokinetic) measurements will be collected before 3BNC117-LS infusion, at the end of the infusion, and at multiple time points during study follow up. Samples will also be collected for measurement of HIV-1 plasma RNA levels before 3BNC117-LS infusion (screen, pre-infusion and day 0) and at all follow up visits in Groups 2B and 2C. All participants will be followed for 48 weeks after 3BNC117-LS administration.

Conditions

• Human Immunodeficiency Virus

Interventions

Type	Name	Description
DRUG	3BNC117-LS	Intravenous infusion of 3BNC117-LS
DRUG	Placebo	Placebo

Timeline

• Start date: 2017-09-13
• Primary completion: 2020-12-31
• Completion: 2020-12-31
• First posted: 2017-08-18
• Last updated: 2021-02-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study