Safety, PK and Antiviral Activity of PGT121 Monoclonal Antibody in HIV-uninfected and HIV-infected Adults

• ClinicalTrials.gov Identifier: NCT02960581
• Recruitment Status: Completed
• First Posted: November 9, 2016
• Last Update Posted: September 17, 2019
• Sponsor: International AIDS Vaccine Initiative
• Collaborators: Beth Israel Deaconess Medical Center, Boston MA; Ragon Institute of MGH, MIT and Harvard, Boston MA; University of Texas Health, Houston AIDS Research Team (HART), Houston TX; Mills Clinical Research, Los Angeles CA; Orlando Immunology Clinic, Orlando FL
• Information provided by (Responsible Party): International AIDS Vaccine Initiative

Study Description

Brief Summary:

This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGT121 monoclonal antibody for HIV prevention and therapy.

Condition or disease	Intervention/treatment	Phase
HIV Infection	Biological: PGT121 3mg/kg IV; Biological: PGT121 10mg/kg IV; Biological: PGT121 30mg/kg IV; Biological: PGT121 3mg/kg SC; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))	Phase 1

Detailed Description:

This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGT121 monoclonal antibody for HIV prevention and therapy. PGT121 mAb is a recombinant human IgG1 monoclonal antibody that targets a V3 glycan-dependent epitope region of the HIV envelope protein. PGT121 mAb was chosen for this study because it is potent, neutralizes a wide array of HIV viruses, and can prevent and treat simian-human immunodeficiency virus (SHIV) in rhesus monkeys.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 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 PGT121 Monoclonal Antibody (mAb) in HIV-uninfected and HIV-infected Adults
• Actual Study Start Date: November 2016
• Actual Primary Completion Date: July 8, 2019
• Actual Study Completion Date: July 8, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1A; HIV-uninfected participants	Biological: PGT121 3mg/kg IV; 3mg/kg administered by IV Infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 1B; HIV-uninfected participants	Biological: PGT121 10mg/kg IV; 10mg/kg administered by IV infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 1C; HIV-uninfected participants	Biological: PGT121 30mg/kg IV; 30mg/kg administered by IV infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 2A; HIV-infected on ART, (<50 cp/ml)	Biological: PGT121 3mg/kg IV; 3mg/kg administered by IV Infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 2B; HIV-infected on ART, (<50 cp/ml)	Biological: PGT121 10mg/kg IV; 10mg/kg administered by IV infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 2C; HIV-infected on ART, (<50 cp/ml)	Biological: PGT121 30mg/kg IV; 30mg/kg administered by IV infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 3A; HIV-Infected off ART (VL 2x10^3 - 1x10^5 cp/ml)	Biological: PGT121 30mg/kg IV; 30mg/kg administered by IV infusion
Experimental: Group 3B; HIV-Infected off ART (VL 1x10^2 - 2x10^3 cp/ml)	Biological: PGT121 30mg/kg IV; 30mg/kg administered by IV infusion
Experimental: Arm 1D; HIV-uninfected participants	Biological: PGT121 3mg/kg SC; 3mg/kg administered by SC injection Placebo: None; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))

Outcome Measures

Primary Outcome Measures :

1. Proportion of participants with PGT121 mAb reactogenicity, related AEs and SAEs [ Time Frame: 6 Months post infusion ]

   The investigators will measure the following endpoints to evaluate the safety and tolerability of PGT121 mAb in HIV-uninfected and HIV-infected adults:

   1. Proportion of participants with moderate or greater reactogenicity (e.g., solicited adverse events) for 3 days following IV infusion of PGT121 mAb.
   2. Proportion of participants with moderate or greater and/or PGT121 mAb-related unsolicited adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, following IV infusion of PGT121 mAb for the first 56 days post administration of Investigational Product.
   3. Proportion of participants with PGT121 mAb-related serious adverse events (SAEs) throughout the study period.
2. Pharmacokinetics: elimination half-life (t1/2) [ Time Frame: 6 Months post infusion ]
   Pharmacokinetics: elimination half-life (t1/2)
3. Pharmacokinetics: Clearance (CL/F) [ Time Frame: 6 Months post infusion ]
   Pharmacokinetics: Clearance (CL/F)
4. Pharmacokinetics: Volume of distribution (Vz/F) [ Time Frame: 6 months post infusion ]
   Pharmacokinetics: Volume of distribution (Vz/F)
5. Pharmacokinetics: Area under the concentration decay curve (AUC) [ Time Frame: 6 months post infusion ]
   Pharmacokinetics: Area under the concentration decay curve (AUC)
6. Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure [ Time Frame: 6 months post infusion ]
   Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure
7. Antiviral Activity [ Time Frame: 6 Months post infusion ]
   Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)

Eligibility Criteria

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

Criteria

Group 1 Inclusion Criteria:

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

Group 1 Exclusion Criteria:

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

Group 2 Inclusion Criteria:

• HIV-infected males or females age 18-65 years old
• On a stable antiretroviral regimen with HIV-1 RNA plasma level <50 copies/ml, CD4 cell count greater than or equal to 300 cells/uL

Group 2 Exclusion Criteria:

• history of AIDS-defining illness within the previous 5 years, significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities

Group 3 Inclusion Criteria:

• HIV-infected males or females age 18-65
• Not on antiretroviral therapy for > 6 months with detectable HIV-1 viral load between 100 and 100,000 copies/ml, CD4 cell count greater than or equal to 300 cells/uL

Group 3 Exclusion Criteria:

• history of AIDS-defining illness within the previous 5 years, significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities

Contacts and Locations

Locations

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

International AIDS Vaccine Initiative

Beth Israel Deaconess Medical Center, Boston MA

Ragon Institute of MGH, MIT and Harvard, Boston MA

University of Texas Health, Houston AIDS Research Team (HART), Houston TX

Mills Clinical Research, Los Angeles CA

Orlando Immunology Clinic, Orlando FL

Investigators

• Principal Investigator: Kathryn Stephenson, MD MPH; Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research
• Study Chair: Boris Juelg, MD PhD; Ragon Institute

More Information

Additional Information:

International AIDS Vaccine Initiative 

• Responsible Party: International AIDS Vaccine Initiative
• ClinicalTrials.gov Identifier: NCT02960581 History of Changes
• Other Study ID Numbers: IAVI T001
• First Posted: November 9, 2016
• Last Update Posted: September 17, 2019
• Last Verified: September 2019

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; Antiviral Agents; Antibodies; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs; Anti-Infective Agents