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CompletedNCT03205917Updated Sep 14, 2020

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

A Phase 1 interventional study of PGDM1400/Placebo (3mg/kg IV) and PGDM1400/Placebo (10mg/kg IV) in HIV Infections, sponsored by International AIDS Vaccine Initiative. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-09-14.

Sponsored by International AIDS Vaccine Initiative · Phase 1, Interventional, and Prevention

From the registry’s dates

  • Primary completion was Apr 2020, 6 years 5 months ago, and no results have been posted to the registry.
Phase
Phase 1
Study type
Interventional
Enrollment
29
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

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.

Read the detailed 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.

02

Conditions studied

  • HIV Infections

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03

In context

HIV Infections

4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 29 is below the median of 83 across 3,251 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

International AIDS Vaccine Initiative is the lead sponsor of 36 studies on the registry; 6 are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility 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
05

Study design

Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
29 participants (actual)

Study arms

  • Experimental
    Group 1A HIV-Uninfected

    PGDM1400 low dose

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

  • Experimental
    Group 1B HIV-Uninfected

    PGDM1400 mid dose

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

  • Experimental
    Group 1C HIV-Uninfected

    PGDM1400 high dose

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

  • Experimental
    Group 2A HIV-Uninfected

    PGDM1400 + PGT121 low dose

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

  • Experimental
    Group 2B HIV-Uninfected

    PGDM1400 + PGT121 mid dose

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

  • Experimental
    Group 2C HIV-Uninfected

    PGDM1400 + PGT121 high dose

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

  • Experimental
    Group 3A HIV-infected off ART

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

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

  • Experimental
    Group 3B HIV-infected off ART

    PGDM1400 + PGT121 at high dose; HIV + without ART

    Biological: PGDM1400 + PGT121 (MTD IV)

Interventions

  • BiologicalPGDM1400/Placebo (3mg/kg IV)

    3/1 (6/2 if DLT)

  • BiologicalPGDM1400/Placebo (10mg/kg IV)

    3/1 (6/2 if DLT)

  • BiologicalPGDM1400/Placebo (30mg/kg IV)

    3/1 (6/2 if DLT)

  • BiologicalPGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV)

    3/1 (6/2 if DLT)

  • BiologicalPGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV)

    3/1 (6/2 if DLT);

  • BiologicalPGDM1400 + PGT121/Placebo (30mg/kg + 30mg/kg IV)

    3/1 (6/2 if DLT)

  • BiologicalPGDM1400 + PGT121 + VRC07-523LS (20mg/kg + 20mg/kg + 20 mg/kg IV)

    3 (max 9)

  • BiologicalPGDM1400 + PGT121 (MTD IV)

    3 (max 9)

06

What researchers measure

Primary outcomes

  1. Safety and tolerability

    1. Proportion of participants with moderate or greater reactogenicity (e.g., solicited adverse events) for 3 days following IV infusion of PGDM1400 mAb alone, and a combination of PGDM1400 mAb and PGT121 mAb, and a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb 2. Proportion of participants with adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, during the first 56 days following IV infusion of PGDM1400 mAb alone and a combination of PGDM1400 mAb and PGT121 mAb, and a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb, that are moderate or greater, and/or related to PGDM1400 mAb or PGT121 mAb or VRC07-523LS mAb 3. Proportion of participants with SAEs throughout the study period following IV infusion of PGDM1400 mAb alone and a combination of PGDM1400 mAb and PGT121 mAb, and a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb, that are related to PGDM1400 mAb or PGT121 mAb or VRC07-523LS mAb

    Time frame: 6 Months post infusion

  2. Elimination half-life (t1/2)

    Elimination half-life following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults

    Time frame: 6 Months post infusion

  3. Clearance (CL/F)

    Clearance following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults.

    Time frame: 6 months post infusion

  4. Volume of distribution (Vz/F)

    Volume of distribution following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults

    Time frame: 6 months post infusion

  5. Area under the concentration decay curve (AUC)

    AUC following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults

    Time frame: 6 months post infusion

  6. Impact of viral load and/or ART

    Impact of viral load and/or ART on PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb disposition

    Time frame: 6 months post infusion

  7. Antiviral activity of PGDM1400 in combination with PGT121 or PGDM1400 in combination with PGT121 and VRC07-523LS mAbs

    Antiviral activity following IV infusion of PGDM1400 mAb in combination with PGT121 mAb, or PGDM1400 mAb in combination with PGT121 mAb and VRC07-523LS mAb, in viremic HIV-infected adults not on ART: Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)

    Time frame: 6 Months post infusion

Secondary outcomes

  1. Serum antibody titers against bNAbs

    Serum anti-PGDM1400 antibody titers, Serum anti-PGT121 antibody titers and Serum anti-VRC07-523LS antibody titers

    Time frame: 6 Months post infusion

  2. CD4+ T cell count

    Determine if IV infusion of PGDM1400 mAb in combination with PGT121 mAb, or PGDM1400 mAb in combination with PGT121 mAb and VRC07-523LS mAb, has any impact on CD4+ T cell counts in HIV-infected adults. Change in CD4+ T cell count compared to baseline as measured by single platform flow cytometry

    Time frame: 6 Months post infusion

  3. HIV genotyping of circulating virus

    Compare plasma virus genotype activity before and after IV infusion of PGDM1400 mAb in combination with PGT121 mAb, or PGDM1400 mAb in combination with PGT121 mAb and VRC07-523LS mAb to determine if PGDM1400 mAb and PGT121 mAb and/or PGT121VRC07-523LS mAb induced viral escape mutations have developed in viremic HIV-infected adults not on ART Genotypic analysis: Development of sequence variations in epitopes known to result in reduced PGDM1400 mAb and/or PGT121 mAb and/or VRC07-523LS mAb neutralization susceptibility or known to cause resistance to antiretroviral drugs

    Time frame: 6 Months post infusion

  4. HIV phenotyping of circulating virus

    Compare plasma virus phenotypic activity before and after IV infusion of PGDM1400 mAb in combination with PGT121 mAb, or PGDM1400 mAb in combination with PGT121 mAb and VRC07-523LS mAb to determine if PGDM1400 mAb and PGT121 mAb and/or PGT121VRC07-523LS mAb induced viral escape mutations have developed in viremic HIV-infected adults not on ART. Phenotypic analysis: Changes in viral susceptibility to PGDM1400 mAb and/or PGT121 mAb and/or VRC07-523LS mAb neutralization Phenotypic analysis: Changes in viral susceptibility to PGDM1400 mAb and/or PGT121 mAb and/or VRC07-523LS mAb neutralization.

    Time frame: 6 months post infusion

07

Study locations

1 site
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
08

References and documents

Publications

  • Julg B, Stephenson KE, Wagh K, Tan SC, Zash R, Walsh S, Ansel J, Kanjilal D, Nkolola J, Walker-Sperling VEK, Ophel J, Yanosick K, Borducchi EN, Maxfield L, Abbink P, Peter L, Yates NL, Wesley MS, Hassell T, Gelderblom HC, deCamp A, Mayer BT, Sato A, Gerber MW, Giorgi EE, Gama L, Koup RA, Mascola JR, Monczor A, Lupo S, Rolle CP, Arduino R, DeJesus E, Tomaras GD, Seaman MS, Korber B, Barouch DH. Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial. Nat Med. 2022 Jun;28(6):1288-1296. doi: 10.1038/s41591-022-01815-1. Epub 2022 May 12. PubMed 35551291 ↗

Related links

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 14, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03205917
Lead sponsor
International AIDS Vaccine Initiative
Collaborators
Beth Israel Deaconess Medical Center, Ragon Institute of MGH, MIT and Harvard, University of Texas Health, Houston AIDS Research Team (HART), Orlando Immunology Clinic
Responsible party
Sponsor
First posted
Jul 2, 2017
Start date
Oct 23, 2017
Primary completion
Apr 20, 2020
Completion
Apr 20, 2020
Last update
Sep 14, 2020

Study contacts

Boris Juelg, MD, PhD
principal investigator · Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research, Ragon Institute of MGH, MIT and Harvard
Kathryn Stephenson, MD, MPH
study chair · Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2020. You cannot join it, but the record below documents what was studied.

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