Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants

NCT03928821 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 130/HPTN 08938531
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion in healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (10)

• 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-T3: Day 0 and T4: Days 0, 112

• 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-T3: Day 0 and T4: Days 0, 112

• 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-T3: Day 0 and T4: Days 0, 112

• Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4

• 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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4

• 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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4

• 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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4

• 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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4

• The Number (Percentage) of Participants With Lab Grade > 1 for Alanine Aminotransferase (ALT), Creatinine, Hemoglobin, Lymphocyte Count, Neutrophil Count, Platelets, White Blood Cells (WBC) Was Summarized by Arm

  The number (percentage) of participants with lab grade \> 1 for alanine aminotransferase (ALT), creatinine, hemoglobin, lymphocyte count, neutrophil count, platelets, white blood cells (WBC) was summarized by arm

  Measured during Screening, Days 0, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, 448*, and 504* Days with * are only available for T4

• 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. The three participants discontinued treatment in T4 were due to the COVID-19 pandemic lockdown.

  Measured through Month 4

Secondary Outcomes (5)

• Serum Concentration Levels of PGT121, PGDM1400, and VRC07-523LS Among Participants Who Received All Scheduled Product Administrations

  Measured during Screening, Days 0, 3, 6, 14, 28, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448* Days with * are only available for T4

• Magnitudes of TZM-bl Cells Responses Against mAb-specific Env-pseudotyped Viruses Among Participants Who Received All Scheduled Product Administrations

  Measured during Screening, Days 0, 3, 28, 56, 112, 140*, 168*, 224* Days with * are only available for T4

• Serum Concentrations of PGT121, PGDM1400, 10-1074, and VRC07-523LS for All Participants

  Measured during Screening, Days 0, 3, 6, 14, 28, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448* Days with * are only available for T4

• Magnitudes of TZM-bl Cells Responses Against a Panel of Env Pseudotyped Viruses for All Participants

  Measured during Screening, Days 0, 3, 28, 56, 112, 140*, 168*, 224* Days with * are only available for T4

• Magnitude of Neutralizing Activity Against a Panel of Env Pseudotyped Reference Viruses in TZM-bl Cells for All Participants

  Measured during Screening, Days 0*, 3, 28, 56*, 112, 140*, 224* Days with * are only available for T4

Study Arms (4)

Group 1: PGT121 + VRC07-523LS

EXPERIMENTAL

Participants will receive PGT121 and VRC07-523LS administered sequentially in this order at Day 0.

Biological: PGT121; Biological: VRC07-523LS

Group 2: PGDM1400 + VRC07-523LS

EXPERIMENTAL

Participants will receive PGDM1400 and VRC07-523LS administered sequentially in this order at Day 0.

Biological: PGDM1400; Biological: VRC07-523LS

Group 3: 10-1074 + VRC07-523LS

EXPERIMENTAL

Participants will receive 10-1074 and VRC07-523LS administered sequentially in this order at Day 0.

Biological: 10-1074; Biological: VRC07-523LS

Group 4: PGDM1400 + PGT121 + VRC07-523LS

EXPERIMENTAL

Participants will receive PGDM1400, PGT121, and VRC07-523LS administered sequentially in this order at Day 0 and Month 4.

Biological: PGT121; Biological: PGDM1400; Biological: VRC07-523LS

Interventions

PGT121 BIOLOGICAL

20 mg/kg administered intravenously

Group 1: PGT121 + VRC07-523LS; Group 4: PGDM1400 + PGT121 + VRC07-523LS

PGDM1400 BIOLOGICAL

20 mg/kg administered intravenously

Group 2: PGDM1400 + VRC07-523LS; Group 4: PGDM1400 + PGT121 + VRC07-523LS

10-1074 BIOLOGICAL

20 mg/kg administered intravenously

Group 3: 10-1074 + VRC07-523LS

VRC07-523LS BIOLOGICAL

20 mg/kg administered intravenously

Group 1: PGT121 + VRC07-523LS; Group 2: PGDM1400 + VRC07-523LS; Group 3: 10-1074 + VRC07-523LS; Group 4: PGDM1400 + PGT121 + VRC07-523LS

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 the protocol for more information)
• Hemogram/Complete Blood Count
• Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were assigned female sex at birth, greater than or equal to 13.0 g/dL for volunteers 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 count equal to 2,500 to 12,000 cells/mm\^3
• White blood cell (WBC) differential either within institutional normal range or with site clinician approval

You may not qualify if:

• General
• Weight greater than 115 kg
• Blood products received within 120 days before first study product administration, unless eligibility for earlier enrollment is determined by the HVTN 130/HPTN 089 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 HVTN 130/HPTN 089 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 130/HPTN 089 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of humanized or human mAbs, whether licensed or investigational; the HVTN 130/HPTN 089 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies VRC01, VRC01LS, VRC07-523LS, PGT121, PGDM1400, or 10-1074
• Immune System
• Serious adverse reactions to VRC07-523LS, PGT121, PGDM1400, or 10-1074 formulation components (acetate, sucrose, polysorbate 80, histidine, and sorbitol; see the protocol for more information), 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 130/HPTN 089 PSRT (for mAb see criterion above)
• Autoimmune disease (Not excluded from participation: Volunteer 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

Study Sites (4)

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, United States

Location

Harlem Prevention Center CRS

New York, New York, 10027, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Related Publications (1)

• Sobieszczyk ME, Mannheimer S, Paez CA, Yu C, Gamble T, Theodore DA, Chege W, Yacovone M, Hanscom B, Heptinstall J, Seaton KE, Zhang L, Miner MD, Eaton A, Weiner JA, Mayer K, Kalams S, Stephenson K, Julg B, Caskey M, Nussenzweig M, Gama L, Barouch DH, Ackerman ME, Tomaras GD, Huang Y, Montefiori D; HVTN 130/HPTN 089 Study Team. Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial. Lancet HIV. 2023 Oct;10(10):e653-e662. doi: 10.1016/S2352-3018(23)00140-6.

  PMID: 37802566 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 Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Magdalena Sobieszczyk

  Columbia University

  STUDY CHAIR

• Sharon Mannheimer

  Columbia 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: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: April 26, 2019
• Study Start: July 17, 2019
• Primary Completion: March 25, 2021
• Study Completion: March 25, 2021
• Last Updated: July 11, 2022
• Results First Posted: July 11, 2022

Record last verified: 2022-06

Locations

US (4)