HIV InfectionsPhase 1NCT03928821

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

A Phase 1 study testing PGT121, PGDM1400 and 10-1074 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 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 combinations of monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion in healthy, HIV-uninfected adults. 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, PGDM1400 and 10-1074
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 27 participants
Where: 4 sitesUnited States
Study dates: 17 Jul 2019to 25 Mar 2021
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 the protocol for more information)
Laboratory Inclusion Values
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
Platelets equal to 125,000 to 550,000/mm^3
Chemistry
Chemistry panel: Alanine aminotransferase (ALT) less than 1.25 times the institutional upper limit of normal; creatinine less than or equal to 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 one of 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,
Any other contraceptive method approved by the HVTN 130/HPTN 089 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 or 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 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

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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 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
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 less than 20 mg/day and length of therapy less than 14 days.)
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
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 sub-cutaneous 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 volunteer'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 had 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 exclusionary: 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 less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg diastolic. For these volunteers, blood pressure must be less than or equal to 140 mm Hg systolic and less than or equal to 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 greater than or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or equal to 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 three 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 hereditary angioedema, acquired angioedema, or idiopathic angioedema

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Fenway Health (FH) CRS
Boston, Massachusetts, 02215-4302
Vanderbilt Vaccine (VV) CRS
Nashville, Tennessee, 37232-2582
Harlem Prevention Center CRS
New York, New York, 10027
Columbia P&S CRS
New York, New York, 10032-3732

Other trials in United States

About this study

Official title: A Phase 1 Clinical Trial 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 Adult Participants

Read the detailed description

This study will 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.

Participants will initially be enrolled into one of three groups. At Day 0, Groups 1, 2, and 3 will receive dual combinations of mAbs administered sequentially via IV. Group 1 will receive a combination of PGT121 and VRC07-523LS, Group 2 will receive PGDM1400 and VRC07-523LS, and Group 3 will receive 10-1074 and VRC07-523LS.

Study staff will review study data from Groups 1, 2, and 3 and determine if Group 4 may begin to enroll. Participants in Group 4 will receive PGDM1400, PGT121, and VRC07-523LS administered in sequence via IV on Day 0 and at Month 4.

Study duration will be 12 months for participants in Groups 1, 2, and 3, and 16 months for participants in Group 4. Participants will attend several study visits, which may include physical examinations, blood and urine collection, HIV testing and pretest counseling, risk reduction counseling, and questionnaires.

Conditions: HIV Infections
Being tested: PGT121, PGDM1400, 10-1074, 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.

PGT121Biological
20 mg/kg administered intravenously
PGDM1400Biological
20 mg/kg administered intravenously
10-1074Biological
20 mg/kg administered intravenously
VRC07-523LSBiological
20 mg/kg administered intravenously

Study groups in NCT03928821
Study group	Role	What they receive
Group 1: PGT121 + VRC07-523LS	Experimental	Participants will receive PGT121 and VRC07-523LS administered sequentially in this order at Day 0. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: PGT121; Biological: PGDM1400; 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-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: 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: 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: 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: 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: 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: 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: 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: 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: Measured through Month 4

Secondary outcomes (5)

Serum Concentration Levels of PGT121, PGDM1400, and VRC07-523LS Among Participants Who Received All Scheduled Product Administrations
Serum PGDM1400, PGT121, and VRC07-523LS IgG levels were measured on a Bio-Plex instrument (Bio-Rad) using a validated assay designed to simultaneously measure infused PGDM1400, PGT121, and VRC07-523LS by its ability to bind anti-idiotype antibody captured on fluorescent magnetic beads. This assay was derived from a standardized custom HIV-1 Luminex assay. PGDM1400, PGT121 and VRC07-523LS were titrated and combined to create a standard curve that was used to determine concentration of the diluted samples. The negative controls were CH58 (an irrelevant mAb) and blank beads.Serum 10-1074 level was measured by anti-idotypic ELISA. Participant serum sample was incubated in anti-ID coated micro-plate well. A conjugated secondary antibody was used to detect bound 10-1074. Samples were titrated to ensure positive optical density (O.D.) readouts fall within the linear range of the assay for monoclonal antibody concentration calculations.
Measured: 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
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped viruses sensitive to the bnAbs (i.e., bnAb-specific viruses) in each infusion group.
Measured: 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
Serum PGDM1400, PGT121, and VRC07-523LS IgG levels were measured on a Bio-Plex instrument (Bio-Rad) using a validated assay designed to simultaneously measure infused PGDM1400, PGT121, and VRC07-523LS by its ability to bind anti-idiotype antibody captured on fluorescent magnetic beads. This assay was derived from a standardized custom HIV-1 Luminex assay. PGDM1400, PGT121 and VRC07-523LS were titrated and combined to create a standard curve that was used to determine concentration of the diluted samples. The negative controls were CH58 (an irrelevant mAb) and blank beads.Serum 10-1074 level was measured by anti-idotypic ELISA. Participant serum sample was incubated in anti-ID coated micro-plate well. A conjugated secondary antibody was used to detect bound 10-1074. Samples were titrated to ensure positive optical density (O.D.) readouts fall within the linear range of the assay for monoclonal antibody concentration calculations
Measured: 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
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped viruses sensitive to the bnAbs (i.e., bnAb-specific viruses) in each infusion group.
Measured: 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
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped viruses sensitive to the bnAbs (i.e., bnAb-specific viruses) in each infusion group.
Measured: Measured during Screening, Days 0*, 3, 28, 56*, 112, 140*, 224* Days with * are only available for T4

Timeline

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

17 Jul 201925 Mar 2021

First posted26 Apr 2019
Study start17 Jul 2019
Primary completion25 Mar 2021
Study completion25 Mar 2021

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: Parallel groups
Masking: None (open label)
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03928821
Sponsor's protocol ID: HVTN 130/HPTN 089
Other IDs: 38531
Status last verified: Jun 2022
First submitted: 23 Apr 2019
Last updated: 11 Jul 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 37802566

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 11 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Clinical Trial 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 Adult Participants
ClinicalTrials.gov ID: NCT03928821
Acronym / sponsor ID: HVTN 130/HPTN 089
Conditions: HIV Infections
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 27 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: 17 Jul 2019 (actual)
Primary completion: 25 Mar 2021 (actual)
Study completion: 25 Mar 2021 (actual)
First posted: 26 Apr 2019 (actual)
Results: Posted 11 Jul 2022

Clinical summary

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

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Group 1: PGT121 + VRC07-523LS	Experimental	Biological: PGT121, Biological: VRC07-523LSParticipants will receive PGT121 and VRC07-523LS administered sequentially in this order at Day 0.
Group 2: PGDM1400 + VRC07-523LS	Experimental	Biological: PGDM1400, Biological: VRC07-523LSParticipants will receive PGDM1400 and VRC07-523LS administered sequentially in this order at Day 0.
Group 3: 10-1074 + VRC07-523LS	Experimental	Biological: 10-1074, Biological: VRC07-523LSParticipants will receive 10-1074 and VRC07-523LS administered sequentially in this order at Day 0.
Group 4: PGDM1400 + PGT121 + VRC07-523LS	Experimental	Biological: PGT121, Biological: PGDM1400, Biological: VRC07-523LSParticipants will receive PGDM1400, PGT121, and VRC07-523LS administered sequentially in this order at Day 0 and Month 4.

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 (42 listed)

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

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
PGT12120 mg/kg administered intravenously	Biological	Group 1: PGT121 + VRC07-523LS, Group 4: PGDM1400 + PGT121 + VRC07-523LS
PGDM140020 mg/kg administered intravenously	Biological	Group 2: PGDM1400 + VRC07-523LS, Group 4: PGDM1400 + PGT121 + VRC07-523LS
10-107420 mg/kg administered intravenously	Biological	Group 3: 10-1074 + VRC07-523LS
VRC07-523LS20 mg/kg administered intravenously	Biological	Group 1: PGT121 + VRC07-523LS, Group 2: PGDM1400 + VRC07-523LS, Group 3: 10-1074 + VRC07-523LS, Group 4: PGDM1400 + PGT121 + VRC07-523LS

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-T3: Day 0 and T4: Days 0, 112
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-T3: Day 0 and T4: Days 0, 112
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-T3: Day 0 and T4: Days 0, 112
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 - Alanine Aminotransferase (ALT) in U/L
Time frame: Measured during Screening, Days 0, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
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
Time frame: 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
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
Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
Time frame: Measured through Month 4
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.

5 secondary outcomes

Serum Concentration Levels of PGT121, PGDM1400, and VRC07-523LS Among Participants Who Received All Scheduled Product Administrations
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Measured during Screening, Days 0*, 3, 28, 56*, 112, 140*, 224* Days with * are only available for T4

Results and safety

Results posted to the registry on 11 Jul 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
T1: PGT121 + VRC07-523LS mo 0	6	6
T2: PGDM1400 + VRC07-523LS mo 0	6	3
T3: 10-1074 + VRC07-523LS	6	3
T4: PGT121 + PGDM1400 + VRC07-523LS mo(0, 4)	9	8

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-T3: Day 0 and T4: Days 0, 112. Count of participants. Unit: Participants

Measure	T1: PGT121 + VRC07-523LS mo 0 n = 6	T2: PGDM1400 + VRC07-523LS mo 0 n = 6	T3: 10-1074 + VRC07-523LS n = 6	T4: PGT121 + PGDM1400 + VRC07-523LS mo(0, 4) n = 9
None	5	6	6	7
Mild	1	0	0	2
Moderate	0	0	0	0
Severe	0	0	0	0
Potentially life-threatening	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-T3: Day 0 and T4: Days 0, 112. Count of participants. Unit: Participants

Measure	T1: PGT121 + VRC07-523LS mo 0 n = 6	T2: PGDM1400 + VRC07-523LS mo 0 n = 6	T3: 10-1074 + VRC07-523LS n = 6	T4: PGT121 + PGDM1400 + VRC07-523LS mo(0, 4) n = 9
Erythema/redness: None	6	6	6	9
Erythema/redness: Not Gradable	0	0	0	0
Erythema/redness: Gr 1: 2.5 to less than 5 cm dim.	0	0	0	0
Erythema/redness: Gr 2: 5 to less than 10 cm dim.	0	0	0	0
Erythema/redness: Gr 3: >=10 cm dim.	0	0	0	0
Erythema/redness: Gr 3: Complications AE	0	0	0	0
Erythema/redness: Gr 4: Complications AE	0	0	0	0
Induration/swelling: None	5	6	6	9

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

Time frame: Measured through 3 days after each vaccine dose at T1-T3: Day 0 and T4: Days 0, 112. Count of participants. Unit: Participants

Measure	T1: PGT121 + VRC07-523LS mo 0 n = 6	T2: PGDM1400 + VRC07-523LS mo 0 n = 6	T3: 10-1074 + VRC07-523LS n = 6	T4: PGT121 + PGDM1400 + VRC07-523LS mo(0, 4) n = 9
Arthralgia: None	5	5	5	9
Arthralgia: Mild	1	1	1	0
Arthralgia: Moderate	0	0	0	0
Arthralgia: Severe	0	0	0	0
Arthralgia: Potentially life-threatening	0	0	0	0
Chills: None	6	4	6	7
Chills: Mild	0	1	0	2
Chills: Moderate	0	1	0	0

Primary outcome: Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT) in U/L

Time frame: Measured during Screening, Days 0, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4. Median (Inter-Quartile Range). Unit: U/L

Measure	T1: PGT121 + VRC07-523LS mo 0 n = 6	T2: PGDM1400 + VRC07-523LS mo 0 n = 6	T3: 10-1074 + VRC07-523LS n = 6	T4: PGT121 + PGDM1400 + VRC07-523LS mo(0, 4) n = 9
Alanine Aminotransferase (U/L)-Baseline	15 (14 to 20)	14 (12 to 15)	13 (10 to 17)	14 (12 to 15)
Alanine Aminotransferase (U/L)-Day 0	14 (8 to 17)	12 (10 to 17)	13 (10 to 16)	14 (10 to 16)
Alanine Aminotransferase (U/L)-Day 14	14 (13 to 15)	16 (11 to 21)	11 (10 to 12)	12 (10 to 16)
Alanine Aminotransferase (U/L)-Day 56	13 (9 to 19)	15 (11 to 21)	20 (12 to 21)	16 (13 to 17)
Alanine Aminotransferase (U/L)-Day 84	–	–	–	13 (12 to 15)
Alanine Aminotransferase (U/L)-Day 112	17 (8 to 23)	9 (9 to 27)	16 (14 to 17)	15 (11 to 15)
Alanine Aminotransferase (U/L)-Day 140	–	–	–	18 (9 to 20)
Alanine Aminotransferase (U/L)-Day 168	14 (8 to 24)	11 (10 to 16)	17 (16 to 18)	17 (17 to 17)

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.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: The study Unsolicited AE reporting time frame is from study enrollment of a trial participant to (and including) Day 336 for T1-T3 and Day 448 for T4. The Solicited AE assessment were collected through 3 full days after each vaccination (vaccinations were given at Day 0 for T1-T4 and Day 112 for T4).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
T1: PGT121 + VRC07-523LS mo 0	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
T2: PGDM1400 + VRC07-523LS mo 0	1 of 6 (16.7%)	6 of 6 (100%)	1 of 6
T3: 10-1074 + VRC07-523LS	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
T4: PGT121 + PGDM1400 + VRC07-523LS mo(0, 4)	0 of 9 (0%)	4 of 9 (44.4%)	0 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37802566Sobieszczyk 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.

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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.

Magdalena Sobieszczyk study chair

Columbia University

Sharon Mannheimer study chair

Columbia University

4 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, PGDM1400 and 10-1074 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 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 42 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 11 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 11 Jul 2022). 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-T3: Day 0 and T4: Days 0, 112). The study lists 10 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 NCT03928821, 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 11 Jul 2022.