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Trial record 5 of 11 for:    T002

A Clinical Trial of PGDM1400 and PGT121 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 : November 29, 2017
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Ragon Institute of MGH, MIT and Harvard
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 mAbs for HIV prevention and therapy.

Condition or disease Intervention/treatment Phase
HIV Infections Biological: PGDM1400/Placebo - 3mg/mL IV Biological: PGDM1400/Placebo - 310mg/mL IV Biological: PGDM1400/Placebo -30mg/mL IV Biological: PGDM1400 + PGT121/Placebo - 3mg/mL + 3mg/mL IV Biological: PGDM1400 + PGT121/Placebo - 10mg/mL + 10mg/mL IV Biological: PGDM1400 + PGT121/Placebo - 30mg/mL + 30mg/mL IV Biological: PGDM1400 Biological: PGDM1400+PGT121 Phase 1

Detailed Description:
This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGDM1400 and PGT121 mAbs for HIV prevention and therapy. PGDM1400 mAb and PGT121 mAb are recombinant human IgG1 monoclonal antibodies that target a V1V2 (PGDM1400) and a V3 glycan-dependent (PGT121) epitope region of the HIV envelope protein (Jardine, Julien et al. 2013, Sok, Doores et al. 2014). PGT121 and PGDM1400 mAb were chosen for this study because they are potent, neutralize a wide array of HIV viruses, and can prevent and treat simian-human immunodeficiency virus (SHIV) in rhesus monkeys.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 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 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults
Actual Study Start Date : October 23, 2017
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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

Experimental: Group 1B (PGDM1400/Placebo)
HIV-Uninfected
Biological: PGDM1400/Placebo - 310mg/mL IV
3/1 (6/2 if DLT); 10mg/mL IV

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

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

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

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

Experimental: Group 3A (PGDM1400 )
HIV-infected off ART (VL 2x103 - 1x105 copies/ml)
Biological: PGDM1400
6 (max 18); MTD IV

Experimental: Group 3B (PGDM1400+PGT121 )
HIV-infected off ART (VL 2x103 - 1x105 copies/ml)
Biological: PGDM1400+PGT121
6 (max 18); MTD IV




Primary Outcome Measures :
  1. Proportion of participants with PGDM1400 and/or PGT121 related AE, SAEs and reactogenicity [ Time Frame: 6 Months post infusion ]
    • Proportion of participants with moderate or greater reactogenicity (e.g., solicited adverse events) following IV infusion of PGDM1400 ± PGT121 mAb.
    • Proportion of participants with adverse events (AEs), including safety laboratory (biochemical, hematological) parameters following IV infusion of PGDM1400 ± PGT121 mAb that are moderate or greater and/or related to PGDM1400 or PGT121 mAb.
    • Proportion of participants with serious adverse events (SAEs) throughout the study period following IV infusion of PGDM1400 ± PGT121 mAb that are related to PGDM1400 or PGT121 mAb.


Secondary Outcome Measures :
  1. Pharmacokinetics of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults- elimination half-life (t1/2) [ Time Frame: 6 Months post infusion ]
  2. Pharmacokinetics of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults- clearance (CL/F) [ Time Frame: 6 Months post infusion ]
  3. Pharmacokinetics of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults- volume of distribution (Vz/F) [ Time Frame: 6 Months post infusion ]
  4. Pharmacokinetics of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults- area under the concentration decay curve (AUC) [ Time Frame: 6 Months post infusion ]
  5. Impact of viral load on PGDM1400 mAb and PGT121 mAb disposition (elimination half-life (t1/2), clearance (CL/F), volumne of distribution (Vz/F), total exposure [ Time Frame: 6 Months post infusion ]
  6. Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values) [ Time Frame: 6 Months post infusion ]


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

Group 1 and 2 Inclusion Criteria:

• Willing to maintain low risk behavior for HIV infection

Group 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 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
Contact: Frances Priddy, MD, MPH +1-212-328-7461 fpriddy@iavi.org

Locations
United States, Massachusetts
Beth Isreal 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
Investigators
Principal Investigator: Boris Juleg, 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:
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: November 29, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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