HIV InfectionsPhase 1NCT04212091

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

A Phase 1 study testing PGT121.414.LS and VRC07-523LS in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: HIV Infections
What is being tested?: PGT121.414.LS and VRC07-523LS
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 33 participants
Where: 5 sitesUnited States
Study dates: 10 Nov 2020to 18 Jan 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

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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).
Laboratory Inclusion Values:
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
Platelets = 125,000 to 550,000 cells/mm^3
Chemistry
Chemistry panel: alanine aminotransferase (ALT) <1.25 times the institutional upper limit of normal; creatinine ≤ institutional upper limit of normal
Virology
Negative HIV-1 and -2 blood test: US volunteers must have a negative Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA).
Negative Hepatitis B surface antigen (HBsAg)
Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive
Urine
Negative or trace urine protein
Reproductive Status
Volunteers who were assigned female sex at birth: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to study product administration on the day of initial study product administration. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing
Reproductive status: A volunteer who was assigned female sex at birth must:
Agree to use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception is defined as using the following methods:
Condoms (male or female) with or without a spermicide,
Diaphragm or cervical cap with spermicide,
Intrauterine device (IUD),
Hormonal contraception,
Tubal ligation, or
Any other contraceptive method approved by the HIV Vaccine Trials Network (HVTN) 136/HIV Prevention Trials Network (HPTN) 092 Protocol Safety Review Team (PSRT)
Successful vasectomy in any partner assigned male sex at birth (considered successful if a volunteer reports that a male partner has [1] documentation of azoospermia by microscopy, or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy);
Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy;
Or be sexually abstinent.
Volunteers who were assigned female sex at birth must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit

Who cannot join

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

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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
Immunosuppressive medications received within 30 days before first study product administration (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatological condition; or [4] a single course of oral/parenteral prednisone or equivalent at doses <20 mg/day and length of therapy <14 days.)
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
Clinically significant medical conditions
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:
A process that would affect the immune response,
A process that would require medication that affects the immune response,
Any contraindication to repeated infusions, or blood draws, including inability to establish venous or subcutaneous access,
A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,
A condition or process (eg, chronic urticaria or recent injection or infusion with evidence of residual inflammation) for which signs or symptoms could be confused with reactions to the study product, or
Any condition specifically listed among the exclusion criteria.
Any medical, psychiatric, occupational, or skin condition (eg, tattoos) that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety, Solicited AEs, or a participant's ability to give informed consent
Psychiatric condition that 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.
Current anti-tuberculosis (TB) therapy
Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report).
Exclude a volunteer who:
Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or
Uses moderate/high-dose, inhaled corticosteroids, or
In the past year has either of the following:
Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids;
Needed emergency care, urgent care, hospitalization, or intubation for asthma.
Diabetes mellitus type 1 or type 2 (Not excluded: type 2 cases controlled with diet alone or a history of isolated gestational diabetes.)
Hypertension:
If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently ≤140 mm Hg systolic and ≤90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤150 mm Hg systolic and ≤100 mm Hg diastolic. For these volunteers, blood pressure must be ≤140 mm Hg systolic and ≤90 mm Hg diastolic at enrollment.
If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥150 mm Hg at enrollment or diastolic blood pressure ≥100 mm Hg at enrollment.
Bleeding disorder diagnosed by a clinician (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study)
Seizure disorder: History of seizure(s) within past 3 years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
Asplenia: any condition resulting in the absence of a functional spleen
History of generalized urticaria, angioedema, or anaphylaxis.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, 02115-6110
The Hope Clinic of the Emory Vaccine Center CRS
Decatur, Georgia, 30030
UCLA CARE Center CRS
Los Angeles, California, 90035
Columbia P&S CRS
New York, New York, 10032
George Washington Univ. CRS
Washington D.C., District of Columbia, 20037-1894

Other trials in United States

About this study

Official title: A Phase 1 Dose-escalation Clinical Trial 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

Read the detailed description

This study will 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 (IV) or subcutaneous (SC) infusions in healthy, HIV-uninfected adult participants.

The study will be conducted in two parts (Part A and B). Part A will include four groups (Groups 1, 2, 3, and 4) and Part B will include two groups (Groups 5 and 6).

In Part A of the study, PGT121.414.LS will be administered via IV infusion at 3, 10, or 30 mg/kg (Groups 1-3) or via SC infusion at 5 mg/kg (Group 4). Participants in Part B will receive consecutive administration of PGT121.414.LS followed by VRC07-523LS, at 20 mg/kg IV each per dose (Group 5) or 5 mg/kg SC each per dose (Group 6). Participants will be followed for 32 weeks after the last study product administration via IV infusion and 24 weeks after the last study product administration via SC infusion.

Participants in Groups 1, 2, and 3 will attend 8 months of study visits. Participants in Group 4 will attend 6 months of study visits. Part B participants will attend 16 months of study visits. Study visits may include physical examinations, blood and urine collection, and questionnaires.

Conditions: HIV Infections
Being tested: PGT121.414.LS, VRC07-523LS
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PGT121.414.LSBiological
Administered via IV infusion or SC infusion, depending on the arm
VRC07-523LSBiological
Administered via IV infusion or SC infusion, depending on the arm

Study groups in NCT04212091
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: PGT121.414.LS; Biological: VRC07-523LS

What is being measured

The primary outcome is the main question the study is designed to answer.

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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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
Measured: 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.
Measured: Day 3, Months 1, 2, 4, 6, 8, 10, 12

Secondary outcomes (2)

Occurrence of Antidrug Antibodies (ADA)
Antidrug antibodies (ADA) are most typically detected and characterized using a tiered testing strategy. In Tier I, a sensitive binding assay is used to determine if samples may have ADA present. In Tier II, the response is confirmed, typically by establishing the specificity of the response by competition with free drug. In Tier III, the response is characterized, typically with a neutralization reduction assay and/or a titering assay.
Measured: 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
Magnitude-breadth characterize the magnitude (ID50 or ID80 titers) and breadth (number of virus isolates) of each individual serum sample assayed against a panel of virus isolates. MB curves show, for each possible magnitude threshold, the fraction of assays with magnitudes greater than this threshold. The area under the magnitude-breadth curve (AUC-MB) is calculated as the average of the log10-based ID50 or ID80 titers over the panel of isolates. Isolates includes: 0330.v4.c3, 3426.v5.c17, 377.v4.c09, AC10.0.29, Ce1176_A3, DU156.12, DU172.17, PVO.4, RHPA4259.7, SC422661.8, T2638, andTRO.11.
Measured: Months 1, 4, and 9

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Nov 202018 Jan 2023

First posted26 Dec 2019
Study start10 Nov 2020
Primary completion18 Jan 2023
Study completion18 Jan 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 33 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04212091
Sponsor's protocol ID: HVTN 136/HPTN 092
Other IDs: 38634
Status last verified: May 2024
First submitted: 23 Dec 2019
Last updated: 13 Dec 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 39667379

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Dose-escalation Clinical Trial 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
ClinicalTrials.gov ID: NCT04212091
Acronym / sponsor ID: HVTN 136/HPTN 092
Conditions: HIV Infections
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 33 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Collaborators: HIV Vaccine Trials Network, HIV Prevention Trials Network
Study start: 10 Nov 2020 (actual)
Primary completion: 18 Jan 2023 (actual)
Study completion: 18 Jan 2023 (actual)
First posted: 26 Dec 2019 (actual)
Results: Posted 13 Dec 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The study will be conducted in two parts (Part A and B). Part A will include four groups (Groups 1, 2, 3, and 4) and Part B will include two groups (Groups 5 and 6).

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Part A (Group 1): PGT121.414.LS (3 mg/kg)	Experimental	Biological: PGT121.414.LSParticipants will receive 3 mg/kg of PGT121.414.LS by intravenous (IV) infusion at Month 0.
Part A (Group 2): PGT121.414.LS (10 mg/kg)	Experimental	Biological: PGT121.414.LSParticipants will receive 10 mg/kg of PGT121.414.LS by IV infusion at Month 0.
Part A (Group 3): PGT121.414.LS (30 mg/kg)	Experimental	Biological: PGT121.414.LSParticipants will receive 30 mg/kg of PGT121.414.LS by IV infusion at Month 0.
Part A (Group 4): PGT121.414.LS (5 mg/kg)	Experimental	Biological: PGT121.414.LSParticipants will receive 5 mg/kg of PGT121.414.LS by subcutaneous (SC) infusion at Month 0.
Part B (Group 5): PGT121.414.LS + VRC07-523LS (20 mg/kg)	Experimental	Biological: PGT121.414.LS, Biological: VRC07-523LSParticipants 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.
Part B (Group 6): PGT121.414.LS + VRC07-523LS (5 mg/kg)	Experimental	Biological: PGT121.414.LS, Biological: VRC07-523LSParticipants 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.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (39 listed)

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

Key exclusion criteria (43 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PGT121.414.LSAdministered via IV infusion or SC infusion, depending on the arm	Biological	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)
VRC07-523LSAdministered via IV infusion or SC infusion, depending on the arm	Biological	Part B (Group 5): PGT121.414.LS + VRC07-523LS (20 mg/kg), Part B (Group 6): PGT121.414.LS + VRC07-523LS (5 mg/kg)

Primary outcome

Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
Time frame: Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224
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
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
Time frame: Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224
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
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Time frame: Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224
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
Chemistry and Hematology Laboratory Measures - Alkaline Phosphatase, AST, ALT in U/L
Time frame: Measured during Screening, Days 0, 112, 168
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Chemistry and Hematology Laboratory Measures - Creatinine in mg/dL
Time frame: Measured during Screening, Days 0, 112, 168
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL
Time frame: Measured during Screening, Days 0, 112, 168
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count in 1000 Cells/Cubic mm
Time frame: Measured during Screening, Days 0, 112, 168
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Chemistry and Hematology Laboratory Measures - Platelets, WBC in 1000 Cells/Cubic mm
Time frame: Measured during Screening, Days 0, 112, 168
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population
Number of Participants Reporting Unsolicited Adverse Events (AEs)
Time frame: Measured through Month 24
The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm
Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
Time frame: Measured through Month 8
The number (percentage) of participants with early discontinuation of vaccinations and reason for discontinuation was summarized by arm
Number of Participants With Early Study Termination and Reason for Early Study Termination
Time frame: Measured through Month 16
The number (percentage) of participants with early study termination and reason for early study termination was summarized by arm
PGT121.414.LS and VRC07523LS Serum Concentrations
Time frame: 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
Serum concentrations of PGT121.414.LS and VRC07-523LS at prespecified timepoints among participants who received all scheduled product administrations
Magnitude of Serum Neutralizing Activity Measured With mAb-specific Env-pseudotyped Viruses in TZM-bl Cells
Time frame: Day 3, Months 1, 2, 4, 6, 8, 10, 12
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.

2 secondary outcomes

Occurrence of Antidrug Antibodies (ADA)
Time frame: 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
Time frame: Months 1, 4, and 9

Results and safety

Results posted to the registry on 13 Dec 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1: Vaccine	3	3
Group 2: Vaccine	4	4
Group 3: Vaccine	3	3
Group 4: Vaccine	3	3
Group 5: Vaccine	10	8
Group 6: Vaccine	10	9

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

Time frame: Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224. Count of participants. Unit: Participants

Measure	Group 1: Vaccine n = 3	Group 2: Vaccine n = 3	Group 3: Vaccine n = 3	Group 4: Vaccine n = 3	Group 5: Vaccine n = 10	Group 6: Vaccine n = 10
None	3	3	3	3	4	3
Mild	0	0	0	0	4	7
Moderate	0	0	0	0	2	0
Severe	0	0	0	0	0	0
Potentially Life-threatening	0	0	0	0	0	0

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

Time frame: Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224. Count of participants. Unit: Participants

Measure	Group 1: Vaccine n = 3	Group 2: Vaccine n = 3	Group 3: Vaccine n = 3	Group 4: Vaccine n = 3	Group 5: Vaccine n = 10	Group 6: Vaccine n = 10
Erythema/Redness: None	3	3	3	3	10	4
Erythema/Redness: Mild	0	0	0	0	0	4
Erythema/Redness: Moderate	0	0	0	0	0	2
Erythema/Redness: Severe	0	0	0	0	0	0
Erythema/Redness: Potentially Life-threatening	0	0	0	0	0	0
Induration/Swelling: None	3	3	3	3	10	4
Induration/Swelling: Mild	0	0	0	0	0	4
Induration/Swelling: Moderate	0	0	0	0	0	2

Primary outcome: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms

Time frame: Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224. Count of participants. Unit: Participants

Measure	Group 1: Vaccine n = 3	Group 2: Vaccine n = 3	Group 3: Vaccine n = 3	Group 4: Vaccine n = 3	Group 5: Vaccine n = 10	Group 6: Vaccine n = 10
Malaise and/or fatigue: None	3	1	2	2	4	5
Malaise and/or fatigue: Mild	0	2	1	1	4	4
Malaise and/or fatigue: Moderate	0	0	0	0	2	1
Malaise and/or fatigue: Severe	0	0	0	0	0	0
Malaise and/or fatigue: Potentially Life-threatening	0	0	0	0	0	0
Myalgia: None	3	3	3	2	8	9
Myalgia: Mild	0	0	0	1	2	1
Myalgia: Moderate	0	0	0	0	0	0

Primary outcome: Chemistry and Hematology Laboratory Measures - Alkaline Phosphatase, AST, ALT in U/L

Time frame: Measured during Screening, Days 0, 112, 168. Median (Inter-Quartile Range). Unit: U/L

Measure	Group 1: Vaccine n = 3	Group 2: Vaccine n = 3	Group 3: Vaccine n = 3	Group 4: Vaccine n = 3	Group 5: Vaccine n = 10	Group 6: Vaccine n = 10
ALT (SGPT) (U/L)- Screening	14.0 (11.0 to 23.0)	14.0 (12.0 to 18.0)	14.0 (14.0 to 24.0)	17.0 (12.0 to 19.0)	13.0 (12.0 to 18.0)	16.0 (11.0 to 24.0)
ALT (SGPT) (U/L)- Day 0/Enrollment	17.0 (11.0 to 25.0)	13.0 (12.0 to 16.0)	15.0 (14.0 to 23.0)	14.0 (13.0 to 17.0)	15.0 (13.0 to 23.0)	15.5 (12.0 to 22.0)
ALT (SGPT) (U/L)- Day 112	13.0 (10.0 to 21.0)	15.0 (10.0 to 19.0)	14.0 (13.0 to 21.0)	15.0 (12.0 to 19.0)	15.0 (13.0 to 18.0)	18.0 (9.0 to 26.0)
ALT (SGPT) (U/L)- Day 168	12.0 (12.0 to 20.0)	17.0 (11.0 to 18.0)	15.0 (12.0 to 20.0)	13.0 (13.0 to 21.0)	20.0 (15.0 to 21.0)	15.0 (11.0 to 19.0)
AST (U/L)- Day 0/Enrollment	18.0 (14.0 to 23.0)	20.0 (19.0 to 22.0)	18.0 (16.0 to 19.0)	19.0 (14.0 to 20.0)	19.0 (16.0 to 23.0)	17.0 (13.0 to 24.0)
AST (U/L)- Day 112	16.0 (15.0 to 19.0)	21.0 (15.0 to 24.0)	16.0 (13.0 to 22.0)	15.0 (15.0 to 32.0)	19.0 (17.0 to 20.0)	19.0 (15.0 to 24.0)
AST (U/L)- Day 168	15.0 (14.0 to 19.0)	23.0 (19.0 to 23.0)	15.0 (14.0 to 21.0)	15.0 (12.0 to 24.0)	19.0 (18.0 to 21.0)	17.0 (15.0 to 18.0)
Alkaline Phosphatase(U/L)- Day 0/Enrollment	55.0 (52.0 to 77.0)	46.0 (43.0 to 59.0)	57.0 (36.0 to 72.0)	63.0 (40.0 to 72.0)	61.5 (54.0 to 76.0)	58.0 (50.0 to 75.0)

Population analysed: 'Overall Number of Participants Analyzed' represents participants enrolled and eligible for laboratory assessment. Participants do not have laboratory assessments if they attended the visit but laboratory specimens were not collected, missed the scheduled visit, or terminated participation in the study prior to the scheduled visit. AST and Alkaline Phosphatase data were not collected at screening.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Measured through Month 24 for Unsolicited AEs and Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224 for Solicited AEs. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1: Vaccine	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Group 2: Vaccine	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Group 3: Vaccine	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Group 4: Vaccine	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Group 5: Vaccine	0 of 10 (0%)	10 of 10 (100%)	0 of 10
Group 6: Vaccine	0 of 10 (0%)	10 of 10 (100%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39667379Edupuganti 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Christopher Hurt study chair

University of North Carolina, Chapel Hill

Kathryn Stephenson study chair

Beth Israel Deaconess Medical Center, Harvard University

Srilatha Edupuganti study chair

Emory University

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PGT121.414.LS and VRC07-523LS in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 39 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness (time frame: Measured through 3 days after each vaccine dose at T1-T4: Day 0; T5-T6: Days 0, 112, 224). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04212091, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2024.