Clinical trial NCT03205917: A Clinical Trial of PGDM1400 and PGT121 and VRC07-523LS Monoclonal Antibodies in HIV-infected and HIV-uninfected Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Lead sponsor: International AIDS Vaccine Initiative
Sponsor class: NETWORK
Collaborators: name: Beth Israel Deaconess Medical Center
name: Ragon Institute of MGH, MIT and Harvard
name: University of Texas Health, Houston AIDS Research Team (HART)
name: Orlando Immunology Clinic
First posted: 2017-07-02
Enrollment: 29
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 PGDM1400 and PGT121 and VRC07-523LS mAbs 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 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.

Eligibility 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

Primary outcomes:
measure: Safety and tolerability
timeFrame: 6 Months post infusion
measure: Elimination half-life (t1/2)
timeFrame: 6 Months post infusion
measure: Clearance (CL/F)
timeFrame: 6 months post infusion
measure: Volume of distribution (Vz/F)
timeFrame: 6 months post infusion
measure: Area under the concentration decay curve (AUC)
timeFrame: 6 months post infusion
measure: Impact of viral load and/or ART
timeFrame: 6 months post infusion
measure: Antiviral activity of PGDM1400 in combination with PGT121 or PGDM1400 in combination with PGT121 and VRC07-523LS mAbs
timeFrame: 6 Months post infusion
Secondary outcomes:
measure: Serum antibody titers against bNAbs
timeFrame: 6 Months post infusion
measure: CD4+ T cell count
timeFrame: 6 Months post infusion
measure: HIV genotyping of circulating virus
timeFrame: 6 Months post infusion
measure: HIV phenotyping of circulating virus
timeFrame: 6 months post infusion
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, Ragon Institute of MGH, MIT and Harvard
name: Boris Juelg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research
name: Kathryn Stephenson, MD, MPH
role: STUDY_CHAIR
References:
citation: Julg B, Stephenson KE, Wagh K, Tan SC, Zash R, Walsh S, Ansel J, Kanjilal D, Nkolola J, Walker-Sperling VEK, Ophel J, Yanosick K, Borducchi EN, Maxfield L, Abbink P, Peter L, Yates NL, Wesley MS, Hassell T, Gelderblom HC, deCamp A, Mayer BT, Sato A, Gerber MW, Giorgi EE, Gama L, Koup RA, Mascola JR, Monczor A, Lupo S, Rolle CP, Arduino R, DeJesus E, Tomaras GD, Seaman MS, Korber B, Barouch DH. Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial. Nat Med. 2022 Jun;28(6):1288-1296. doi: 10.1038/s41591-022-01815-1. Epub 2022 May 12.