Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of the Monoclonal Antibody PGT121.414.LS Administered Alone and in Combination With VRC07-523LS Via Intravenous or Subcutaneous Infusions in Healthy, HIV-uninfected Adult Participants

NCT04212091 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 136/HPTN 09238634
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS via intravenous or subcutaneous infusions in healthy, HIV-uninfected adult participants.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (13)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented

  Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented

  Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: malaise and/or fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and body temperature. The item Max. Systemic Symptoms is the maximum of the individual systemic reactogenicities excluding body temperature for a participant

  Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224

• Chemistry and Hematology Laboratory Measures - Alkaline Phosphatase, AST, ALT in U/L

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population

  Measured during Screening, Days 0, 112, 168

• Chemistry and Hematology Laboratory Measures - Creatinine in mg/dL

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population

  Measured during Screening, Days 0, 112, 168

• Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population

  Measured during Screening, Days 0, 112, 168

• Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count in 1000 Cells/Cubic mm

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population

  Measured during Screening, Days 0, 112, 168

• Chemistry and Hematology Laboratory Measures - Platelets, WBC in 1000 Cells/Cubic mm

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population

  Measured during Screening, Days 0, 112, 168

• Number of Participants Reporting Unsolicited Adverse Events (AEs)

  The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm

  Measured through Month 24

• Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation

  The number (percentage) of participants with early discontinuation of vaccinations and reason for discontinuation was summarized by arm

  Measured through Month 8

• Number of Participants With Early Study Termination and Reason for Early Study Termination

  The number (percentage) of participants with early study termination and reason for early study termination was summarized by arm

  Measured through Month 16

• PGT121.414.LS and VRC07523LS Serum Concentrations

  Serum concentrations of PGT121.414.LS and VRC07-523LS at prespecified timepoints among participants who received all scheduled product administrations

  Days 0, 0.0417, 1, 2, 3, 6, 14, 28, 56, 84, 112, 112.0417, 140, 168, 196, 224, 224.0417, 252, 280, 336, 392, 448

• Magnitude of Serum Neutralizing Activity Measured With mAb-specific Env-pseudotyped Viruses in TZM-bl Cells

  Level of ID50 and ID80 titer data from the TZMbl neutralizing antibody assays against 1 bnAb-specific virus (CH505TF.N334S.N160A.N280D.1, sensitive to PGT121, resistant to VRC07) for all Part A participants (IV or SC administration of PGT121.414.LS alone), and 1 bnAb-specific virus (CNE55.N160K, sensitive to VRC07, resistant to PGT121) for all Part B participants (IV or SC administration of PGT121.414.LS in combination with VRC07523LS) at all expected timepoints.

  Day 3, Months 1, 2, 4, 6, 8, 10, 12

Secondary Outcomes (2)

• Occurrence of Antidrug Antibodies (ADA)

  Day 0, 112, 196, 224, 336, 392, 448

• Magnitude and Breadth of Neutralizing Antibody Responses Against Autologous Viral Isolates as Assessed by Area Under the Magnitude-breadth Curves at Months 1, 4, and 9

  Months 1, 4, and 9

Study Arms (6)

Part A (Group 1): PGT121.414.LS (3 mg/kg)

EXPERIMENTAL

Participants will receive 3 mg/kg of PGT121.414.LS by intravenous (IV) infusion at Month 0.

Biological: PGT121.414.LS

Part A (Group 2): PGT121.414.LS (10 mg/kg)

EXPERIMENTAL

Participants will receive 10 mg/kg of PGT121.414.LS by IV infusion at Month 0.

Biological: PGT121.414.LS

Part A (Group 3): PGT121.414.LS (30 mg/kg)

EXPERIMENTAL

Participants will receive 30 mg/kg of PGT121.414.LS by IV infusion at Month 0.

Biological: PGT121.414.LS

Part A (Group 4): PGT121.414.LS (5 mg/kg)

EXPERIMENTAL

Participants will receive 5 mg/kg of PGT121.414.LS by subcutaneous (SC) infusion at Month 0.

Biological: PGT121.414.LS

Part B (Group 5): PGT121.414.LS + VRC07-523LS (20 mg/kg)

EXPERIMENTAL

Participants will receive 20 mg/kg of PGT121.414.LS and 20 mg/kg of VRC07-523LS by IV infusion sequentially in this order at Months 0, 4, and 8.

Biological: PGT121.414.LS; Biological: VRC07-523LS

Part B (Group 6): PGT121.414.LS + VRC07-523LS (5 mg/kg)

EXPERIMENTAL

Participants will receive 5 mg/kg of PGT121.414.LS and 5 mg/kg of VRC07-523LS by SC infusion sequentially in this order at Months 0, 4, and 8.

Biological: PGT121.414.LS; Biological: VRC07-523LS

Interventions

PGT121.414.LS BIOLOGICAL

Administered via IV infusion or SC infusion, depending on the arm

Part A (Group 1): PGT121.414.LS (3 mg/kg); Part A (Group 2): PGT121.414.LS (10 mg/kg); Part A (Group 3): PGT121.414.LS (30 mg/kg); Part A (Group 4): PGT121.414.LS (5 mg/kg); Part B (Group 5): PGT121.414.LS + VRC07-523LS (20 mg/kg); Part B (Group 6): PGT121.414.LS + VRC07-523LS (5 mg/kg)

VRC07-523LS BIOLOGICAL

Administered via IV infusion or SC infusion, depending on the arm

Part B (Group 5): PGT121.414.LS + VRC07-523LS (20 mg/kg); Part B (Group 6): PGT121.414.LS + VRC07-523LS (5 mg/kg)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria
• Age of 18 to 50 years
• Access to a participating Clinical Research Site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• HIV-Related Criteria:
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit (see study protocol).
• Hemogram/Complete Blood Count
• Hemoglobin ≥11.0 g/dL for participants who were assigned female sex at birth, ≥13.0 g/dL for participants who were assigned male sex at birth. For transgender participants who have been on feminizing hormone therapy for more than 6 consecutive months, determine hemoglobin eligibility based on the gender with which they identify (ie, a transgender female who has been on hormone therapy for more than 6 consecutive months should be assessed for eligibility using the hemoglobin parameters for persons assigned female sex at birth).
• White blood cell (WBC) count = 2,500 to 12,000 cells/mm\^3
• WBC differential either within institutional normal range or with site clinician approval

You may not qualify if:

• General
• Weight \>115 kg
• Blood products received within 120 days before first study product administration, unless eligibility for earlier enrollment is determined by the HVTN 136/HPTN 092 PSRT
• Investigational research agents received within 30 days before first study product administration
• Intent to participate in another study of an investigational research agent or any other study that requires non-Network HIV antibody testing during the planned duration of the study
• Pregnant or breastfeeding
• Vaccines and other Injections
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 136/HPTN 092 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of humanized or human mAbs, whether licensed or investigational; the HVTN 136/HPTN 092 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies VRC01, VRC01LS, VRC07-523LS, or PGT121
• Immune System
• Serious adverse reactions to VRC07-523LS or PGT121.414.LS formulation components (acetate, sucrose, polysorbate 80, histidine, and sorbitol; see study protocol), including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain
• Immunoglobulin received within 90 days before first study product administration, unless eligibility for earlier enrollment is determined by the HVTN 136/HPTN 092 PSRT (for mAb see criterion above)
• Autoimmune disease (Not excluded from participation: Participant with mild, stable and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate Solicited and Unsolicited AE assessments)
• Immunodeficiency

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• HIV Vaccine Trials Network: collaborator
• HIV Prevention Trials Network: collaborator

Study Sites (5)

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

George Washington Univ. CRS

Washington D.C., District of Columbia, 20037-1894, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115-6110, United States

Location

Columbia P&S CRS

New York, New York, 10032, United States

Location

Related Publications (1)

• Edupuganti S, Hurt CB, Stephenson KE, Huang Y, Paez CA, Yu C, Yen C, Hanscom B, He Z, Miner MD, Gamble T, Heptinstall J, Seaton KE, Domin E, Lin BC, McKee K, Doria-Rose N, Regenold S, Spiegel H, Anderson M, McClosky N, Zhang L, Piwowar-Manning E, Ackerman ME, Pensiero M, Dye BJ, Landovitz RJ, Mayer K, Siegel M, Sobieszczyk M, Walsh SR, Gama L, Barouch DH, Montefiori DC, Tomaras GD; HVTN 136/HPTN 092 Study Team. Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial. Lancet HIV. 2025 Jan;12(1):e13-e25. doi: 10.1016/S2352-3018(24)00247-9. Epub 2024 Dec 10.

  PMID: 39667379 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Christopher Hurt

  University of North Carolina, Chapel Hill

  STUDY CHAIR

• Kathryn Stephenson

  Beth Israel Deaconess Medical Center, Harvard University

  STUDY CHAIR

• Srilatha Edupuganti

  Emory University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2019
• First Posted: December 26, 2019
• Study Start: November 10, 2020
• Primary Completion: January 18, 2023
• Study Completion: January 18, 2023
• Last Updated: December 13, 2024
• Results First Posted: December 13, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)