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

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ClinicalTrials.gov Identifier: NCT03205917
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : September 4, 2019
Sponsor:
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
Information provided by (Responsible Party):
International AIDS Vaccine Initiative

Brief 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.

Condition or disease Intervention/treatment Phase
HIV Infections Biological: PGDM1400/Placebo (3mg/kg IV) Biological: PGDM1400/Placebo (10mg/kg IV) Biological: PGDM1400/Placebo (30mg/kg IV) Biological: PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV) Biological: PGDM1400 + PGT121/Placebo (10mg/kg + 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 (MTD IV) Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 1 Randomized Placebo-controlled Clinical Trial of the Safety, Pharmacokinetics and Antiviral Activity of PGDM1400 and PGT121 and VRC07-523LS Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults
Actual Study Start Date : October 23, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Group 1A HIV-Uninfected
PGDM1400 low dose
Biological: PGDM1400/Placebo (3mg/kg IV)
3/1 (6/2 if DLT)

Experimental: Group 1B HIV-Uninfected
PGDM1400 mid dose
Biological: PGDM1400/Placebo (10mg/kg IV)
3/1 (6/2 if DLT)

Experimental: Group 1C HIV-Uninfected
PGDM1400 high dose
Biological: PGDM1400/Placebo (30mg/kg IV)
3/1 (6/2 if DLT)

Experimental: Group 2A HIV-Uninfected
PGDM1400 + PGT121 low dose
Biological: PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV)
3/1 (6/2 if DLT)

Experimental: Group 2B HIV-Uninfected
PGDM1400 + PGT121 mid dose
Biological: PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV)
3/1 (6/2 if DLT);

Experimental: Group 2C HIV-Uninfected
PGDM1400 + PGT121 high dose
Biological: PGDM1400 + PGT121/Placebo (30mg/kg + 30mg/kg IV)
3/1 (6/2 if DLT)

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)
3 (max 9)

Experimental: Group 3B HIV-infected off ART
PGDM1400 + PGT121 at high dose; HIV + without ART
Biological: PGDM1400 + PGT121 (MTD IV)
3 (max 9)




Primary Outcome Measures :
  1. Safety and tolerability [ Time Frame: 6 Months post infusion ]
    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

  2. Elimination half-life (t1/2) [ Time Frame: 6 Months post infusion ]
    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

  3. Clearance (CL/F) [ Time Frame: 6 months post infusion ]
    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.

  4. Volume of distribution (Vz/F) [ Time Frame: 6 months post infusion ]
    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

  5. Area under the concentration decay curve (AUC) [ Time Frame: 6 months post infusion ]
    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. Impact of viral load and/or ART [ Time Frame: 6 months post infusion ]
    Impact of viral load and/or ART on PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb disposition

  7. Antiviral activity of PGDM1400 in combination with PGT121 or PGDM1400 in combination with PGT121 and VRC07-523LS mAbs [ Time Frame: 6 Months post infusion ]

    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)



Secondary Outcome Measures :
  1. Serum antibody titers against bNAbs [ Time Frame: 6 Months post infusion ]
    Serum anti-PGDM1400 antibody titers, Serum anti-PGT121 antibody titers and Serum anti-VRC07-523LS antibody titers

  2. CD4+ T cell count [ Time Frame: 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

  3. HIV genotyping of circulating virus [ Time Frame: 6 Months post infusion ]

    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


  4. HIV phenotyping of circulating virus [ Time Frame: 6 months post infusion ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03205917


Contacts
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Contact: Dagna Laufer, MD +1-212-328-7459 dlaufer@iavi.org

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Boris D Juelg, MD, PhD    857-268-7088    bjuelg@bidmc.harvard.edu   
Sponsors and Collaborators
International AIDS Vaccine Initiative
Beth Israel Deaconess Medical Center
Ragon Institute of MGH, MIT and Harvard
University of Texas Health, Houston AIDS Research Team (HART)
Orlando Immunology Clinic
Investigators
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Principal Investigator: Boris Juelg, MD, PhD Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research, Ragon Institute of MGH, MIT and Harvard
Study Chair: Kathryn Stephenson, MD, MPH Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research

Additional Information:
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Responsible Party: International AIDS Vaccine Initiative
ClinicalTrials.gov Identifier: NCT03205917     History of Changes
Other Study ID Numbers: IAVI T002
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs