Clinical trial NCT02960581: Safety, PK and Antiviral Activity of PGT121 Monoclonal Antibody in HIV-uninfected and HIV-infected Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infection
Lead sponsor: International AIDS Vaccine Initiative
Sponsor class: NETWORK
Collaborators: name: Beth Israel Deaconess Medical Center, Boston MA
name: Ragon Institute of MGH, MIT and Harvard, Boston MA
name: University of Texas Health, Houston AIDS Research Team (HART), Houston TX
name: Mills Clinical Research, Los Angeles CA
name: Orlando Immunology Clinic, Orlando FL
First posted: 2016-11-09
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Proportion of participants with PGT121 mAb reactogenicity, related AEs and SAEs
timeFrame: 6 Months post infusion
measure: Pharmacokinetics: elimination half-life (t1/2)
timeFrame: 6 Months post infusion
measure: Pharmacokinetics: Clearance (CL/F)
timeFrame: 6 Months post infusion
measure: Pharmacokinetics: Volume of distribution (Vz/F)
timeFrame: 6 months post infusion
measure: Pharmacokinetics: Area under the concentration decay curve (AUC)
timeFrame: 6 months post infusion
measure: Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure
timeFrame: 6 months post infusion
measure: Antiviral Activity
timeFrame: 6 Months post infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research
name: Kathryn Stephenson, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Ragon Institute
name: Boris Juelg, MD PhD
role: STUDY_CHAIR
References:
citation: Stephenson KE, Julg B, Tan CS, Zash R, Walsh SR, Rolle CP, Monczor AN, Lupo S, Gelderblom HC, Ansel JL, Kanjilal DG, Maxfield LF, Nkolola J, Borducchi EN, Abbink P, Liu J, Peter L, Chandrashekar A, Nityanandam R, Lin Z, Setaro A, Sapiente J, Chen Z, Sunner L, Cassidy T, Bennett C, Sato A, Mayer B, Perelson AS, deCamp A, Priddy FH, Wagh K, Giorgi EE, Yates NL, Arduino RC, DeJesus E, Tomaras GD, Seaman MS, Korber B, Barouch DH. Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial. Nat Med. 2021 Oct;27(10):1718-1724. doi: 10.1038/s41591-021-01509-0. Epub 2021 Oct 7.