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| Name | Class |
|---|---|
| Beth Israel Deaconess Medical Center | OTHER |
| Ragon Institute of MGH, MIT and Harvard | OTHER |
| University of Texas Health, Houston AIDS Research Team (HART) | UNKNOWN |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1A HIV-Uninfected | Experimental | PGDM1400 low dose |
|
| Group 1B HIV-Uninfected | Experimental | PGDM1400 mid dose |
|
| Group 1C HIV-Uninfected | Experimental | PGDM1400 high dose |
|
| Group 2A HIV-Uninfected | Experimental | PGDM1400 + PGT121 low dose |
|
| Group 2B HIV-Uninfected | Experimental | PGDM1400 + PGT121 mid dose |
|
| Group 2C HIV-Uninfected | Experimental | PGDM1400 + PGT121 high dose |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PGDM1400/Placebo (3mg/kg IV) | Biological | 3/1 (6/2 if DLT) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability |
| 6 Months post infusion |
| 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 | 6 Months post infusion |
| 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. | 6 months post infusion |
| 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 | 6 months post infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Serum antibody titers against bNAbs | Serum anti-PGDM1400 antibody titers, Serum anti-PGT121 antibody titers and Serum anti-VRC07-523LS antibody titers | 6 Months post infusion |
| CD4+ T cell count |
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Groups 1 and 2 Inclusion Criteria:
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:
Group 3 Exclusion Criteria:
• Significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities
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| Name | Affiliation | Role |
|---|---|---|
| Boris Juelg, MD, PhD | Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research, Ragon Institute of MGH, MIT and Harvard | Principal Investigator |
| Kathryn Stephenson, MD, MPH | Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35551291 | Derived | 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. |
| Label | URL |
|---|---|
| IAVI Website | View source |
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| Orlando Immunology Clinic |
| UNKNOWN |
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| Group 3A HIV-infected off ART | Experimental | PGDM1400 + PGT121 + VRC07-523LS at 20mg/kg; HIV+ without ART |
|
| Group 3B HIV-infected off ART | Experimental | PGDM1400 + PGT121 at high dose; HIV + without ART |
|
| PGDM1400/Placebo (10mg/kg IV) |
| Biological |
3/1 (6/2 if DLT) |
|
| PGDM1400/Placebo (30mg/kg IV) | Biological | 3/1 (6/2 if DLT) |
|
| PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV) | Biological | 3/1 (6/2 if DLT) |
|
| PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV) | Biological | 3/1 (6/2 if DLT); |
|
| PGDM1400 + PGT121/Placebo (30mg/kg + 30mg/kg IV) | Biological | 3/1 (6/2 if DLT) |
|
| PGDM1400 + PGT121 + VRC07-523LS (20mg/kg + 20mg/kg + 20 mg/kg IV) | Biological | 3 (max 9) |
|
| PGDM1400 + PGT121 (MTD IV) | Biological | 3 (max 9) |
|
| 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 | 6 months post infusion |
| 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 | 6 months post infusion |
| 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) | 6 Months post infusion |
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
| 6 Months post infusion |
| 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 | 6 Months post infusion |
| 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. | 6 months post infusion |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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