A Phase 1/2a Study of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults

NCT03721510 | Completed Phase 1 FDA Drug

• 1 other identifier: IAVI T003
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1/2a open label study to evaluate the safety, tolerability, pharmacokinetics and anti-viral activity of PGT121, VRC07-523LS and PGDM1400 for HIV prevention and therapy.

Conditions

HIV/AIDS

Keywords

HIV; AIDS; Monoclonal antibodies; Neutralizing antibodies; Analytical treatment interruption

Outcome Measures

Primary Outcomes (7)

• Safety and Tolerability - Proportion of volunteers with moderate or greater reactogenicity

  Proportion of volunteers with moderate or greater reactogenicity (i.e., solicited adverse events) for 3 days following each IV infusion of PGT121, VRC07-523LS and PGDM1400 as assessed using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, July 2017, or the Common Terminology Criteria for Adverse Events (CTCAE,) Version 5.0 27 November 2017 (for reactogenicity observed within the first 24 hours post-infusion.)

  3 days post infusion for each infusion

• Safety and Tolerability - Proportion of volunteers with adverse events (AEs)

  Proportion of volunteers with adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, during the 56 days following IV infusion of PGT121, VRC07-523LS and PGDM1400 that are moderate or greater, and/or considered related to PGT121 and/or VRC07-523LS and/or PGDM1400 as assessed using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or the Common Terminology Criteria for Adverse Events (CTCAE,) Version 5.0 27 November 2017 (for reactogenicity observed within the first 24 hours post-infusion.)

  56 days

• Safety and Tolerability - Proportion of volunteers with serious adverse events (SAEs)

  Proportion of volunteers with serious adverse events (SAEs) throughout the study period following IV infusion(s) of PGT121, VRC07-523LS and PGDM1400 that are considered related to PGT121 and/or VRC07-523LS and/or PGDM1400 as assessed using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or the Common Terminology Criteria for Adverse Events (CTCAE,) Version 5.0 27 November 2017 (for reactogenicity observed within the first 24 hours post-infusion.)

  Up to 44 weeks

• Pharmacokinetics - Elimination half-life (t1/2)

  Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults: • Elimination half-life (t1/2)

  Up to 44 weeks

• Pharmacokinetics - Clearance (CL/F)

  Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults: • Clearance (CL/F)

  Up to 44 weeks

• Pharmacokinetics - Volume of distribution (Vz/F)

  Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults: • Volume of distribution (Vz/F)

  Up to 44 weeks

• Pharmacokinetics - Area under the concentration decay curve (AUC)

  Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults: • Area under the concentration decay curve (AUC)

  Up to 44 weeks

Secondary Outcomes (10)

• Antiviral Activity - Proportion of volunteers who meet ART re-initiation criteria

  Up to 44 weeks

• Antiviral Activity - Time to meeting ART re-initiation criteria

  Up to 44 weeks

• mAb serum levels at the time of viral rebound in Group 2

  Up to 44 weeks

• mAb serum levels at the time of viral rebound in Group 2

  Up to 44 weeks

• mAb serum levels at the time of viral rebound in Group 2

  Up to 44 weeks

Study Arms (3)

Group 1A

ACTIVE COMPARATOR

HIV-uninfected volunteers receiving one IV infusion

Biological: PGT121 + VRC07-523LS

Group 1B

ACTIVE COMPARATOR

HIV-uninfected volunteers receiving one IV infusion

Biological: PGT121 + VRC07-523LS + PGDM1400

Group 2

ACTIVE COMPARATOR

HIV-infected volunteers on ART receiving three or six IV infusions

Biological: PGT121 + VRC07-523LS + PGDM1400

Interventions

PGT121 + VRC07-523LS BIOLOGICAL

PGT121 + VRC07-523LS, dose 30 mg/kg each, given intravenously

Group 1A

PGT121 + VRC07-523LS + PGDM1400 BIOLOGICAL

PGT121 + VRC07-523LS + PGDM1400, dose 20 mg/kg each, given intravenously

Group 1B; Group 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or female, including transgender, volunteers, as assessed by a medical history, physical exam, and laboratory test
• At least 18 years of age on the day of screening and has not reached his or her 51st birthday on the day of signing the Informed Consent Document
• Willing to undergo HIV testing, risk reduction counseling and receive HIV test results
• Low risk for HIV infection for 12 months prior to study participation and willing to maintain low-risk behavior for the duration of the trial
• At least 18 years of age on the day of screening and has not reached his or her 66th birthday on the day of signing the Informed Consent Document
• Confirmed HIV-1 infection (HIV Ab+ or HIV RNA+) by documentation in the medical records or in-clinic HIV testing
• CD4 ≥ 400 cells/µl
• On antiretroviral therapy for a minimum of 24 months, with plasma HIV-1 RNA levels of \< 50 copies/ml for at least 12 months as documented in the medical records, and with a viral load \< 50 copies / ml at time of screening (within 56 days prior to IP administration). ART must not have been initiated during the acute phase of the infection as suggested by the available medical history and laboratory data from the time of the diagnosis. Note: ART is defined as a regimen including \> 2 compounds, e.g., 2x nucleoside reverse transcriptase inhibitors plus either non-nucleoside reverse transcriptase inhibitor or protease inhibitor or integrase inhibitor.
• If on an NNRTI-based regimen, willing to switch to an integrase inhibitor containing regimen for 4 weeks prior to discontinuing ART
• No history of AIDS-defining illness within the past 5 years
• No history of CD4 nadir \<200 cells/ul

You may not qualify if:

• Any clinically significant acute or chronic medical condition, other than HIV infection, that is considered progressive or in the opinion of the investigator makes the volunteer unsuitable for participation in the study.
• Any clinically relevant abnormality on history or examination including history of immunodeficiency (other then HIV infection) or autoimmune disease; use of systemic corticosteroids, immunosuppressive, anticancer, or other medications considered significant by the investigator within the previous 6 months. The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least 6 weeks prior to enrollment in this study.
• If born female, pregnant, lactating or planning a pregnancy during the period of screening through completion of the study.
• In the past 6 months a history of alcohol or substance use, including marijuana, judged by the Investigator to potentially interfere with volunteer study compliance.
• Bleeding disorder that was diagnosed by a physician. Note: A volunteer who states that he or she has easy bruising or bleeding, but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience, is eligible.
• History of a splenectomy.
• Receipt of live attenuated vaccine within the previous 30 days or planned receipt within 30 days after administration of investigational product; or receipt of other vaccine within the previous 14 days or planned receipt within 14 days after infusion with investigational product (exception is live attenuated influenza vaccine within 14 days).
• Receipt of blood transfusion or blood-derived products within the previous 3 months.
• Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study. Note: receipt of placebo in a clinical trial in the previous 3 months will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval.
• Prior receipt of an investigational HIV vaccine candidate, monoclonal antibody or polyclonal immunoglobulin. Note: receipt of placebo in a previous HIV vaccine or monoclonal antibody trial will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval.
• History of severe local or systemic reactogenicity to injections or IV infusion (e.g., anaphylaxis, respiratory difficulties, angioedema).
• Psychiatric condition that compromises safety of the volunteer and precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
• If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial.
• Seizure disorder: a volunteer who has had a seizure in the last 3 years is excluded.
• Body mass index ≥ 35 or ≤ 18.5.

Sponsors & Collaborators

• International AIDS Vaccine Initiative: lead
• Beth Israel Deaconess Medical Center: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Orlando Immunology Center: collaborator
• Houston AIDS Research Team: collaborator

Study Sites (3)

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Center for Virology and Vaccine Research/ Clinical Trials Unit/ BIDMC

Boston, Massachusetts, 02215, United States

Location

Houston AIDS Research Team (HART)

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Julg B, Walker-Sperling VEK, Wagh K, Aid M, Stephenson KE, Zash R, Liu J, Nkolola JP, Hoyt A, Castro M, Serebryannyy L, Yanosick K, Speidel T, Borducchi EN, Murzda T, Maxfield L, Arduino R, McDermott AB, Gama L, Giorgi EE, Koup RA, Seaman MS, Rolle CP, DeJesus E, Li W, Korber B, Barouch DH. Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial. Nat Med. 2024 Dec;30(12):3534-3543. doi: 10.1038/s41591-024-03247-5. Epub 2024 Sep 12.

  PMID: 39266747 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2018
• First Posted: October 26, 2018
• Study Start: December 3, 2018
• Primary Completion: October 25, 2021
• Study Completion: May 2, 2022
• Last Updated: May 10, 2022

Record last verified: 2022-05

Locations

US (3)