A Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of PGDM1400LS Alone and in Combination With VRC07-523LS and PGT121.414.LS in Healthy, HIV-uninfected Adult Participants

NCT05184452 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: HVTN 140/HPTN 101DAIDS DOCUMENT ID
• Study Type: interventional
• Target: 95
• Locations: 4 countries
• Sites: 13

Brief Summary

Part A: The purpose of this part of the study is to understand how the body's immune system responds to a new lab-made antibody against HIV. The study is looking to see if the way the antibody is given affects the immune response. The study will also look at whether the antibody is safe to give to people and does not make them too uncomfortable. Part B: The purpose of this part of the study is to understand how the body's immune system responds to lab-made antibodies against HIV when they are given in combination at different doses. The study also wants to see if the way the antibodies are given affects the immune response.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (16)

• 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 Month Measured through 3 days after each vaccine dose at T1-T5: Day 0 and T6-T10: 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 Month Measured through 3 days after each vaccine dose at T1-T5: Day 0 and T6-T10: 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 maximum grade observed for each symptom over the time frame is presented

  Measured through Month Measured through 3 days after each vaccine dose at T1-T5: Day 0 and T6-T10: Days 0, 112

• Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP)

  For each local laboratory measure, summary statistics: median and interquartile range were presented by treatment group and timepoint for the overall population.

  Measured during Screening, Days 0, 56, 112*, 168, and 280* Days with * are only available for T6-T10

• Chemistry and Hematology Laboratory Measures - Creatinine

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

  Measured during Screening, Days 0, 56, 112*, 168, and 280* Days with * are only available for T6-T10

• Chemistry and Hematology Laboratory Measures - Hemoglobin

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

  Measured during Screening, Days 0, 56, 112*, 168, and 280* Days with * are only available for T6-T10

• Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count

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

  Measured during Screening, Days 0, 56, 112*, 168, and 280* Days with * are only available for T6-T10

• Chemistry and Hematology Laboratory Measures - Platelets, White Blood Cells (WBC)

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

  Measured during Screening, Days 0, 56, 112*, 168, and 280* Days with * are only available for T6-T10

• Number of Lab Grade >= 1 for Alanine Aminotransferase (ALT), Creatinine, Hemoglobin, Lymphocyte Count, Neutrophil Count, Platelets, White Blood Cells (WBC).

  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, 56, 112*, 168, and 280* Days with * are only available for T6-T10

• 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 4

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

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

  Measured through Month 6 in Part A and Month 10 in Part B

• Serum Concentration Levels of PGDM1400LS Among Participants Who Received All Scheduled Product Administrations

  Serum concentrations of PGDM1400LS at prespecified timepoints among participants who received all scheduled product administrations

  Measured during Days 0, 0.0417 (1hr post 1st infusion), 3, 6, 28, 56, 112, 112.0417 (1hr post 2nd infusion)*, 168, 224*, and 280* Days with * are only available for T6-T10

• Serum Concentration Levels of PGT121.414LS Among Participants Who Received All Scheduled Product Administrations

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

  Measured during Days 0, 0.0417 (1hr post 1st infusion), 3, 6, 28, 56, 112, 112.0417 (1hr post 2nd infusion), 168, 224, and 280

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

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

  Measured during Days 0, 0.0417 (1hr post 1st infusion), 3, 6, 28, 56, 112, 112.0417 (1hr post 2nd infusion), 168, 224, and 280

• Magnitude of Serum Neutralizing Activity (ie, Neutralizing Antibody Titers, Including ID50, ID80) for

  Magnitude of Serum Neutralizing Activity (ie, Neutralizing Antibody Titers, Including ID50, ID80) for Parts A and B

  Measured during Days 0, 3, 6, 28, 56, 112, 168, 224*, and 280* Days with * are only available for T6-T10

• Magnitude Breadth of Serum Neutralizing Activity (ie, Neutralizing Antibody Titers, Including ID50, ID80) for Parts A and B

  Magnitude breadth of neutralizing activity measured with Env pseudotyped viruses specific for either PGDM1400LS, VRC07-523LS or PGT121.414LS in TZM-bl cells at prespecified timepoints among participants who received all scheduled product administrations for Parts A and B.

  Measured during Days 56 and 168* Days with * are only available for T6-T10

Secondary Outcomes (3)

• Magnitude of Neutralizing Activity Against Env-pseudotyped Viruses in TZM-bl Cells for Part A and B and Clinical Product Assayed at Same Time.

  Day 56 and Day 168* corresponding to Month 2 and Month 6* of the study. Days with * are only available for T6-T10

• Occurrence of Anti-drug Antibodies (ADA) for Participants in Parts A and B

  Measured during Screening, Days 0, 112*, 168†, and 280* Days with † are only available for T1-T5 Days with * are only available for T6-T10

• Anti-drug Antibodies (ADA) Titers for Participants in Parts A and B

  Measured during Screening, Days 0, 112*, 168†, and 280* Days with † are only available for T1-T5 Days with * are only available for T6-T10

Study Arms (10)

PGDM1400LS 5 mg/kg IV

EXPERIMENTAL

Participants will receive PGDM1400LS 5 mg/kg by intravenous (IV) infusion at Month 0

Drug: PGDM1400LS (5mg/kg, IV)

PGDM1400LS 20 mg/kg IV

EXPERIMENTAL

Participants will receive PGDM1400LS 20 mg/kg by IV infusion at Month 0

Drug: PGDM1400LS (20mg/kg, IV)

PGDM1400LS 20 mg/kg SC

EXPERIMENTAL

Participants will receive PGDM1400LS 20 mg/kg by subcutaneous (SC) infusion at Month 0

Drug: PGDM1400LS (20mg/kg, SC)

PGDM1400LS 40 mg/kg IV

EXPERIMENTAL

Participants will receive PGDM1400LS 40 mg/kg by IV infusion at Month 0

Drug: PGDM1400LS (40mg/kg, IV)

PGDM1400LS 40 mg/kg SC

EXPERIMENTAL

Participants will receive PGDM1400LS 40 mg/kg by SC infusion at Month 0

Drug: PGDM1400LS (40mg/kg, SC)

PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg IV

EXPERIMENTAL

Participants will receive PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg by IV infusion sequentially in this order at Month 0 and Month 4

Drug: PGDM1400LS (20mg/kg, IV); Drug: VRC07-523LS (20mg/kg, IV); Drug: PGT121.414.LS (20mg/kg, IV)

PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg SC

EXPERIMENTAL

Participants will receive PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg by SC infusion sequentially in this order at Month 0 and Month 4

Drug: PGDM1400LS (20mg/kg, SC); Drug: VRC07-523LS (20mg/kg, SC); Drug: PGT121.414.LS (20mg/kg, SC)

PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram IV

EXPERIMENTAL

Participants will receive PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram by IV infusion sequentially in this order at Month 0 and Month 4

Drug: PGDM1400LS (1.4g, IV); Drug: VRC07-523LS (1.4g, IV); Drug: PGT121.414.LS (1.4g, IV)

PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram SC

EXPERIMENTAL

Participants will receive PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram by SC infusion sequentially in this order at Month 0 and Month 4

Drug: PGDM1400LS (1.4g, SC); Drug: VRC07-523LS (1.4g, SC); Drug: PGT121.414.LS (1.4g, SC)

PGDM1400LS 40mg/kg + VRC07-523LS 40mg/kg + PGT121.414.LS 40 mg/kg IV

EXPERIMENTAL

Participants will receive PGDM1400LS 40mg/kg + VRC07-523LS 40mg/kg + PGT121.414.LS 40 mg/kg by IV infusion sequentially in this order at Month 0 and Month 4

Drug: PGDM1400LS (40mg/kg, IV); Drug: VRC07-523LS (40mg/kg, IV); Drug: PGT121.414.LS (40mg/kg, IV)

Interventions

PGDM1400LS (5mg/kg, IV) DRUG

5 mg/kg to be administered via IV infusion

PGDM1400LS 5 mg/kg IV

PGDM1400LS (20mg/kg, IV) DRUG

20 mg/kg to be administered via IV infusion

PGDM1400LS 20 mg/kg IV; PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg IV

PGDM1400LS (20mg/kg, SC) DRUG

20 mg/kg to be administered via SC infusion

PGDM1400LS 20 mg/kg SC; PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg SC

PGDM1400LS (40mg/kg, IV) DRUG

40 mg/kg to be administered via IV infusion

PGDM1400LS 40 mg/kg IV; PGDM1400LS 40mg/kg + VRC07-523LS 40mg/kg + PGT121.414.LS 40 mg/kg IV

PGDM1400LS (40mg/kg, SC) DRUG

40 mg/kg to be administered via SC infusion

PGDM1400LS 40 mg/kg SC

PGDM1400LS (1.4g, IV) DRUG

1.4gram to be administered via IV infusion

PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram IV

PGDM1400LS (1.4g, SC) DRUG

1.4gram to be administered via SC infusion

PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram SC

VRC07-523LS (20mg/kg, IV) DRUG

VRC07-523LS 20mg/kg administered via IV infusion

PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg IV

VRC07-523LS (20mg/kg, SC) DRUG

VRC07-523LS 20mg/kg administered via SC infusion

PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg SC

VRC07-523LS (1.4g, IV) DRUG

VRC07-523LS 1.4g administered via IV infusion

PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram IV

VRC07-523LS (1.4g, SC) DRUG

VRC07-523LS 1.4g administered via SC infusion

PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram SC

VRC07-523LS (40mg/kg, IV) DRUG

VRC07-523LS 40mg/kg administered via IV infusion

PGDM1400LS 40mg/kg + VRC07-523LS 40mg/kg + PGT121.414.LS 40 mg/kg IV

PGT121.414.LS (20mg/kg, IV) DRUG

PGT121.414.LS 20mg/kg administered via IV infusion

PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg IV

PGT121.414.LS (20mg/kg, SC) DRUG

PGT121.414.LS 20mg/kg administered via SC infusion

PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg SC

PGT121.414.LS (1.4g, IV) DRUG

PGT121.414.LS 1.4g administered via IV infusion

PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram IV

PGT121.414.LS (1.4g, SC) DRUG

PGT121.414.LS 1.4g administered via SC infusion

PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram SC

PGT121.414.LS (40mg/kg, IV) DRUG

PGT121.414.LS 40mg/kg administered via IV infusion

PGDM1400LS 40mg/kg + VRC07-523LS 40mg/kg + PGT121.414.LS 40 mg/kg IV

Eligibility Criteria

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

You may qualify if:

• Age of 18 through 50 years
• Access to a participating 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
• 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 Appendix J and Appendix K).
• Hemoglobin
• ≥ 11.0 g/dL for volunteers who were assigned female sex at birth
• ≥ 13.0 g/dL for volunteers who were assigned male sex at birth and transgender males who have been on hormone therapy for more than 6 consecutive months
• ≥ 12.0 g/dL for transgender females who have been on hormone therapy for more than 6 consecutive months
• For transgender volunteers who have been on hormone therapy for less than 6 consecutive months, determine hemoglobin eligibility based on the sex assigned at birth
• White blood cell count = 2,500 to 12,000 cells/mm3

You may not qualify if:

• Weight \< 35kg or \> 115 kg
• Blood products received within 120 days before first study product administration, unless eligibility for earlier enrollment is determined by the HVTN 140/HPTN 101 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 140/HPTN 101 study
• Pregnant or breastfeeding
• HIV vaccine(s) received in a prior HIV vaccine trial. Volunteers who have received control/placebo in an HIV vaccine trial are not excluded.
• SARS-CoV-2 vaccine(s) received within 7 days prior to HVTN 140/HPTN 101 enrollment or planned within 7 days after enrollment.
• Receipt of humanized or human mAbs, whether licensed or investigational.
• Previous receipt of mAbs VRC01, VRC01LS, VRC07-523LS, PGDM1400, PGT121, PGT121.414.LS.
• Serious adverse reactions to PGDM1400LS, VRC07-523LS, or PGT121.414.LS formulation components (see Section 8.2) including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
• Immunoglobulin received within 60 days before first study product administration (for mAb see criterion 8 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 CRS investigator, is likely not subject to exacerbation and likely not to complicate Solicited and Unsolicited AE assessments.)
• Immunodeficiency
• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
• Symptoms consistent with COVID-19 or known SARS-CoV-2 infection,

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institutes of Health (NIH): collaborator
• Department of Health and Human Services: collaborator

Study Sites (13)

Bridge HIV CRS

San Francisco, California, 94102, United States

Location

George Washington University

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

Location

The Hope Clinic of the Emory Vaccine Center

Atlanta, Georgia, 30030, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Vanderbilt Vaccine (VV)

Nashville, Tennessee, 37232, United States

Location

Kenya Medical Research Institute (KEMRI)

Kericho, Kenya

Location

CAPRISA eThekweni Clinical Research Site

Berea, Durban, 4001, South Africa

Location

Ward 21 Clinical Research Site

Hillbrow, Johannesburg, 2001, South Africa

Location

Groote Schuur Hospital

Cape Town, Western Cape, 7925, South Africa

Location

Soweto HVTN CRS

Soweto, 1862, South Africa

Location

Seke South Clinical Research Site

Chitungwiza, Harare, Zimbabwe

Location

Milton Park CRS

Milton Park, Harare, Zimbabwe

Location

Spilhaus CRS

Milton Park, Harare, Zimbabwe

Location

Related Publications (1)

• Seaton KE, Paez CA, Yu C, Karuna ST, Gamble T, Miner MD, Heptinstall J, Zhang L, Gao F, Yacovone M, Spiegel H, Dumond JB, Anderson M, Piwowar-Manning E, Dye B, Tindale I, Proulx-Burns L, Trahey M, Takuva S, Takalani A, Bailey VC, Kalams SA, Scott H, Mkhize NN, Weiner JA, Ackerman ME, McElrath MJ, Pensiero M, Barouch DH, Montefiori D, Tomaras GD, Corey L, Cohen MS, Huang Y, Mahomed S, Siegel M, Kelley CF; HVTN 140/HPTN 101 study team. Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, a V2 specific HIV-1 broadly neutralising antibody, infused intravenously or subcutaneously in people without HIV-1 in the USA (HVTN 140/HPTN 101 part A): a first-in-human, phase 1 randomised trial. Lancet HIV. 2025 Jun;12(6):e405-e415. doi: 10.1016/S2352-3018(25)00012-8.

  PMID: 40441807 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

hvtn.covpn.sdmc@hvtn.org

206-667-5812

Study Officials

• Colleen Kelley

  Emory University

  STUDY CHAIR

• Marc Siegel

  George Washington University

  STUDY CHAIR

• Sharana Mahomed

  Centre for the AIDS Programme of Research in South Africa

  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: October 26, 2021
• First Posted: January 11, 2022
• Study Start: November 15, 2021
• Primary Completion: July 19, 2023
• Study Completion: July 19, 2023
• Last Updated: February 10, 2025
• Results First Posted: February 10, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); KE (1); ZA (4); ZI (3)