HVTN 140/HPTN 101

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

Study Summary

Study Documents

Study Details

Protocol Status: Closed to Follow Up
Study Purpose:
Study Design:

Multicenter, randomized, open-label study

Study Population:

About 95 healthy, HIV-1–uninfected volunteers aged 18 through 50 years

Study Size:

95 participants

Study Duration:

6 months per participant in Part A and 10 months per participant in Part B of scheduled clinic visits. 14 months (includes enrollment, planned safety holds, and follow-up).

Treatment Regimen:

Part A
Group 1: PGDM1400LS 5 mg/kg to be administered via IV infusion at Month 0
Group 2: PGDM1400LS 20 mg/kg to be administered via IV infusion at Month 0
Group 3: PGDM1400LS 20 mg/kg to be administered via SC infusion at Month 0
Group 4: PGDM1400LS 40 mg/kg to be administered via IV infusion at Month 0
Group 5: PGDM1400LS 40 mg/kg to be administered via SC infusion at Month 0

Part B
Group 6: PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS
20 mg/kg to be administered via IV infusion sequentially in this order at Month 0
and Month 4
Group 7: PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS
20 mg/kg to be administered via SC infusion sequentially in this order at Month 0
and Month 4
Group 8: PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS
1.4gram to be administered via IV infusion sequentially in this order at Month 0
and Month 4
Group 9: PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS
1.4gram to be administered via SC infusion sequentially in this order at Month 0
and Month 4
Group 10: PGDM1400LS 40mg/kg + VRC07-523LS 40mg/kg + PGT121.414.LS
40 mg/kg to be administered via IV infusion sequentially in this order at Month 0
and Month 4

Primary Objectives:

To evaluate the safety and tolerability of PGDM1400LSwhen 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)•To 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)

Secondary Objectives:

To correlate serum concentrations of PGDM1400LS, VRC07-523LS and PGT121.414.LS with corresponding virus neutralization titers in serum

To determine whether the mAbs maintain their expected combined magnitude and breadth of serum neutralizing activity after each PGDM1400LS, VRC07-523LS and PGT121.414.LS three-mAb administration (Part B) as predicted by the known magnitude and breadth of neutralization of the corresponding mAb combinations as non-infused clinical products

To determine whether anti-drug antibodies (ADA) are present