A Clinical Trial of PGDM1400 and PGT121 and VRC07-523LS Monoclonal Antibodies in HIV-infected and HIV-uninfected Adults

International AIDS Vaccine Initiative

Status and phase: Completed; Phase 1

Conditions: HIV Infections

Treatments: Biological: PGDM1400/Placebo (30mg/kg IV); Biological: PGDM1400 + PGT121 (MTD IV); Biological: PGDM1400/Placebo (10mg/kg IV); Biological: PGDM1400 + PGT121/Placebo (30mg/kg + 30mg/kg IV); Biological: PGDM1400 + PGT121 + VRC07-523LS (20mg/kg + 20mg/kg + 20 mg/kg IV); Biological: PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV); Biological: PGDM1400/Placebo (3mg/kg IV); Biological: PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV)

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT03205917

IAVI T002

Details and patient eligibility

About

This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGDM1400 and PGT121 and VRC07-523LS mAbs for HIV prevention and therapy.

Full description

This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGDM1400, PGT121 and VRC07-523LS mAbs for HIV prevention and therapy. PGDM1400, PGT121 and VRC07-523LS mAbs are recombinant human IgG1 monoclonal antibodies that target V1V2 (PGDM1400), a V3 glycan-dependent epitope (PGT121) and the CD4 binding site (VRC07-523LS) epitope region of the HIV envelope protein. PGT121, PGDM1400 and VRC07-523LS mAb were chosen for this study because of their potency, their ability to neutralize a wide array of cross-clade HIV viruses in a complementary pattern and their proven antiviral activity in animal studies e.g., their capacity to robustly prevent and treat simian-human immunodeficiency virus (SHIV) in rhesus monkeys.

Enrollment: 29 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Groups 1 and 2 Inclusion Criteria:

• HIV-uninfected males or females age 18-50 years old
• Willing to maintain low risk behavior for HIV infection

Groups 1 and 2 Exclusion Criteria:

• Confirmed HIV-infection, pregnancy or lactation, significant acute or chronic disease and clinically significant laboratory abnormalities

Group 3 Inclusion Criteria:

• HIV-infected males or females age 18-65 years old
• Not on antiretroviral therapy with HIV-1 RNA plasma level between 1,000 and 100,000 copies/ml, CD4 cell count ≥ 300 cells/uL

Group 3 Exclusion Criteria:

• Significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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29 participants in 8 patient groups

Group 1A HIV-Uninfected

Experimental group

Description:

PGDM1400 low dose

Treatment:

Biological: PGDM1400/Placebo (3mg/kg IV)

Group 1B HIV-Uninfected

Experimental group

Description:

PGDM1400 mid dose

Treatment:

Biological: PGDM1400/Placebo (10mg/kg IV)

Group 1C HIV-Uninfected

Experimental group

Description:

PGDM1400 high dose

Treatment:

Biological: PGDM1400/Placebo (30mg/kg IV)

Group 2A HIV-Uninfected

Experimental group

Description:

PGDM1400 + PGT121 low dose

Treatment:

Biological: PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV)

Group 2B HIV-Uninfected

Experimental group

Description:

PGDM1400 + PGT121 mid dose

Treatment:

Biological: PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV)

Group 2C HIV-Uninfected

Experimental group

Description:

PGDM1400 + PGT121 high dose

Treatment:

Biological: PGDM1400 + PGT121/Placebo (30mg/kg + 30mg/kg IV)

Group 3A HIV-infected off ART

Experimental group

Description:

PGDM1400 + PGT121 + VRC07-523LS at 20mg/kg; HIV+ without ART

Treatment:

Biological: PGDM1400 + PGT121 + VRC07-523LS (20mg/kg + 20mg/kg + 20 mg/kg IV)

Group 3B HIV-infected off ART

Experimental group

Description:

PGDM1400 + PGT121 at high dose; HIV + without ART

Treatment:

Biological: PGDM1400 + PGT121 (MTD IV)