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

HIV Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02960581
• Other study ID #: IAVI T001
• Status: Completed
• Phase: Phase 1
• Start date: November 2016
• Est. completion date: July 8, 2019

Study information

• Verified date: September 2019
• Source: International AIDS Vaccine Initiative
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: July 8, 2019
• Est. primary completion date: July 8, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Biological:
• PGT121 3mg/kg IV
3mg/kg administered by IV Infusion
• PGT121 10mg/kg IV
10mg/kg administered by IV infusion
• PGT121 30mg/kg IV
30mg/kg administered by IV infusion
• PGT121 3mg/kg SC
3mg/kg administered by SC injection Placebo: None
• Placebo (0.9% Sodium Chloride Injection USP (Saline))

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (6)

Lead Sponsor	Collaborator
International AIDS Vaccine Initiative	Beth Israel Deaconess Medical Center, Boston MA, Mills Clinical Research, Los Angeles CA, Orlando Immunology Clinic, Orlando FL, Ragon Institute of MGH, MIT and Harvard, Boston MA, University of Texas Health, Houston AIDS Research Team (HART), Houston TX

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with PGT121 mAb reactogenicity, related AEs and SAEs	The investigators will measure the following endpoints to evaluate the safety and tolerability of PGT121 mAb in HIV-uninfected and HIV-infected adults: Proportion of participants with moderate or greater reactogenicity (e.g., solicited adverse events) for 3 days following IV infusion of PGT121 mAb.; 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.; Proportion of participants with PGT121 mAb-related serious adverse events (SAEs) throughout the study period.	6 Months post infusion
Primary	Pharmacokinetics: elimination half-life (t1/2)	Pharmacokinetics: elimination half-life (t1/2)	6 Months post infusion
Primary	Pharmacokinetics: Clearance (CL/F)	Pharmacokinetics: Clearance (CL/F)	6 Months post infusion
Primary	Pharmacokinetics: Volume of distribution (Vz/F)	Pharmacokinetics: Volume of distribution (Vz/F)	6 months post infusion
Primary	Pharmacokinetics: Area under the concentration decay curve (AUC)	Pharmacokinetics: Area under the concentration decay curve (AUC)	6 months post infusion
Primary	Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure	Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure	6 months post infusion
Primary	Antiviral Activity	Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)	6 Months post infusion

External Links

•   International AIDS Vaccine Initiative