HIV InfectionsPhase 1NCT03387150

Evaluating the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults

A Phase 1 study testing VRC07-523LS in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in 2 countries.

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, and serum concentrations of a human monoclonal antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and routes to 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?: VRC07-523LS
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 124 participants
Where: 7 sitesin 2 countries
Study dates: 28 Feb 2018to 7 Dec 2020
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 those criteria through the last required protocol clinic visit (see the protocol for more information).
Laboratory Inclusion Values
Hemogram/Complete Blood Count (CBC)
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 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 volunteers assigned female sex at birth).
White blood cell (WBC) count equal to 2,500 to 12,000 cells/mm^3
WBC differential either within institutional normal range or with site physician 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 and creatinine less than or equal to institutional upper limits of normal.
Virology
Negative HIV-1 and -2 blood test: US volunteers must have a negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA). Non-US sites may use locally available assays that have been approved by HVTN and HIV Prevention Trials Network (HPTN) Laboratory Operations.
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 infusion/injection. 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 (see protocol for more information) 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, or
Any other contraceptive method approved by the HVTN 127/HPTN 087 Protocol Safety Review Team (PSRT)
Successful vasectomy in any partner assigned male sex at birth (considered successful if a volunteer reports that a partner assigned male sex at birth 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 tubal ligation;
Or plan to be sexually abstinent until at least 6 months following the last study product administration.
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 127/HPTN 087 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 127/HPTN 087 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 127/HPTN 087 PSRT will determine eligibility on a case-by-case basis.
Previous receipt of humanized or human mAbs, whether licensed or investigational; the HVTN 127/HPTN 087 PSRT will determine eligibility on a case-by-case basis.
Previous receipt of monoclonal antibodies VRC01, VRC01LS, or VRC07-523LS
Immune System
Immunosuppressive medications received within 30 days before first injection or infusion (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of oral/parenteral prednisone or equivalent at doses less than 2 mg/kg/day and length of therapy less than 11 days with completion at least 30 days prior to enrollment)
Serious adverse reactions to VRC07-523LS formulation components, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain
Immunoglobulin received within 90 days before first injection or infusion, unless eligibility for earlier enrollment is determined by the HVTN 127/HPTN 087 PSRT
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 adverse event (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 injections, infusions, or blood draws, including inability to establish venous 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 other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or 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 or moderate, 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 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 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 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 doctor (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

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

United States6 sites

The Ponce de Leon Center CRS
Atlanta, Georgia, 30308-2012
Alabama CRS
Birmingham, Alabama, 35294
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, 02115-6110
Fenway Health (FH) CRS
Boston, Massachusetts, 02215-4302
Chapel Hill CRS
Chapel Hill, North Carolina, 27599
Columbia P&S CRS
New York, New York, 10032-3732

Other trials in United States

Switzerland1 site

Lausanne Vaccine and Immunotherapy Center CRS
Lausanne, Canton of Vaud, 1011

Other trials in Switzerland

About this study

Official title: A Multicenter, Randomized, Partially Blinded Phase 1 Clinical Trial to Evaluate the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults

Read the detailed description

This study will evaluate the safety, tolerability, and serum concentrations of a human monoclonal antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and routes to healthy, HIV-uninfected adults.

Participants will be randomly assigned to one of six groups. Participants in Group 1 will receive 2.5 mg/kg of VRC07-523LS by intravenous (IV) infusion at Weeks 0, 16, 32, 48, and 64. Participants in Group 2 will receive 5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64. Participants in Group 3 will receive 20 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64. Participants in Group 4 will receive 2.5 mg/kg of VRC07-523LS by subcutaneous (SC) injection at Weeks 0, 16, 32, 48, and 64. Participants in Group 5 will receive 5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64. Participants in Group 6 will receive 2.5 mg/kg of VRC07-523LS or placebo by intramuscular (IM) injection at Weeks 0, 16, 32, 48, and 64.

Participants will attend numerous study visits throughout the course of the study, beginning at Week 0 through Week 112. Visits may include physical examinations, blood and urine collection, HIV testing, risk reduction counseling, and questionnaires.

Conditions: HIV Infections
Being tested: VRC07-523LS, Placebo
Medical subject headings: HIV Infections

What participants receive

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

VRC07-523LSBiological
Also called VRC-HIVMAB075-00-AB
Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in
PlaceboBiological
Sodium Chloride for Injection USP, 0.9%; administered by IM injection

Study groups in NCT03387150
Study group	Role	What they receive
Group 1: VRC07-523LS	Experimental	Participants in Group 1 will receive 2.5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64. Receives: Biological: VRC07-523LS
Group 2: VRC07-523LS	Experimental	Participants in Group 2 will receive 5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64. Receives: Biological: VRC07-523LS
Group 3: VRC07-523LS	Experimental	Participants in Group 3 will receive 20 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64. Receives: Biological: VRC07-523LS
Group 4: VRC07-523LS	Experimental	Participants in Group 4 will receive 2.5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64. Receives: Biological: VRC07-523LS
Group 5: VRC07-523LS	Experimental	Participants in Group 5 will receive 5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64. Receives: Biological: VRC07-523LS
Group T6 VRC07-523LS	Experimental	Participants in Group T6 will receive 2.5 mg/kg of VRC07-523LS by IM injection at Weeks 0, 16, 32, 48, and 64. Receives: Biological: VRC07-523LS
Group P6: Placebo	Placebo comparator	Participants in Group P6 will receive 2.5 mg/kg of placebo by IM injection at Weeks 0, 16, 32, 48, and 64. Receives: Biological: Placebo

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 Weeks 0, 16, 32, 48, 64
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 Weeks 0, 16, 32, 48, 64
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 Weeks 0, 16, 32, 48, 64
Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT)
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Measured: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
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: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
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: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
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: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
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: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
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: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
VRC07523LS Serum Concentrations
VRC07523LS serum concentrations measured in healthy human subjects after up to five administrations of the study product via the IV, SC or IM routes at various doses. Serum concentrations between the first and second study product administrations (Target Visit Day 0-112) were measured using ELISA assay in all enrolled participants. Serum concentrations after the second study product administrations (Target Visit Day 168-784) were measured using BAMA (LUMINEX) assay in a subset of participants enrolled in each treatment group and all particiants in plocebo group. serum concentrations below the lower limit of quantification (LLoQ) were replaced by half the LLoQ. Thus, concentrations below the LLoQ when measured by the ELISA assay were replaced by 0.5 ug/ml and concentrations below the LLoQ when measured by the BAMA assay were replaced by 0.02285 ug/ml.
Measured: Target Visit Days 0, 3, 6, 28, 56, 84, 112, 168, 224, 280, 336, 392, 448, 504, 560, 616, 672, 728, 784 (i.e., visit numbers 2 through 20)

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, 6, 112, 224, 448
Magnitude and Breadth of Neutralizing Antibody Responses Against Autologous Viral Isolates as Assessed by Area Under the Magnitude-breadth Curves 8, 72, 88 Weeks After the First Study Product Administration.
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: H703_0646_051sN, H703_1471_190s, H703_1750_140Es, H704_0726_080sN, H704_1535_030sN, H704_2544_140eN01, PVO.4.
Measured: Weeks 8, 72, and 88 following the first study product administration

Timeline

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

28 Feb 20187 Dec 2020

First posted29 Dec 2017
Study start28 Feb 2018
Primary completion7 Dec 2020
Study completion7 Dec 2020

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: 124 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03387150
Sponsor's protocol ID: HVTN 127/HPTN 087
Other IDs: 38458
Status last verified: Apr 2023
First submitted: 21 Dec 2017
Last updated: 5 Apr 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Walsh SR, Gay CL, Karuna ST, Hyrien O, Skalland T, Mayer KH, Sobieszczyk ME, Baden LR, Goepfert PA, Del Rio C, Pantaleo G, Andrew P, Karg C, He Z, Lu H, Paez CA, Baumblatt JAG, Polakowski LL, Chege W, Anderson MA, Janto S, Han X, Huang Y, Dumond J, Ackerman ME, McDermott AB, Flach B, Piwowar-Manning E, Seaton K, Tomaras GD, Montefiori DC, Gama L, Mascola JR; HVTN 127/HPTN 087 Study Team. Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial. PLoS Med. 2024 Jun 24;21(6):e1004329. doi: 10.1371/journal.pmed.1004329. eCollection 2024 Jun.
PubMed 38913710

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 5 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Partially Blinded Phase 1 Clinical Trial to Evaluate the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults
ClinicalTrials.gov ID: NCT03387150
Acronym / sponsor ID: HVTN 127/HPTN 087
Conditions: HIV Infections
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 124 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: 28 Feb 2018 (actual)
Primary completion: 7 Dec 2020 (actual)
Study completion: 7 Dec 2020 (actual)
First posted: 29 Dec 2017 (actual)
Results: Posted 21 Mar 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: 7

Arm	Type	Receives
Group 1: VRC07-523LS	Experimental	Biological: VRC07-523LSParticipants in Group 1 will receive 2.5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64.
Group 2: VRC07-523LS	Experimental	Biological: VRC07-523LSParticipants in Group 2 will receive 5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64.
Group 3: VRC07-523LS	Experimental	Biological: VRC07-523LSParticipants in Group 3 will receive 20 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64.
Group 4: VRC07-523LS	Experimental	Biological: VRC07-523LSParticipants in Group 4 will receive 2.5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64.
Group 5: VRC07-523LS	Experimental	Biological: VRC07-523LSParticipants in Group 5 will receive 5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64.
Group T6 VRC07-523LS	Experimental	Biological: VRC07-523LSParticipants in Group T6 will receive 2.5 mg/kg of VRC07-523LS by IM injection at Weeks 0, 16, 32, 48, and 64.
Group P6: Placebo	Placebo comparator	Biological: PlaceboParticipants in Group P6 will receive 2.5 mg/kg of placebo by IM injection at Weeks 0, 16, 32, 48, and 64.

Who may qualify

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

Key inclusion criteria (38 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 127/HPTN 087 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 127/HPTN 087 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
VRC07-523LSAlso: VRC-HIVMAB075-00-ABAdministered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in	Biological	Group 1: VRC07-523LS, Group 2: VRC07-523LS, Group 3: VRC07-523LS, Group 4: VRC07-523LS, Group 5: VRC07-523LS, Group T6 VRC07-523LS
PlaceboSodium Chloride for Injection USP, 0.9%; administered by IM injection	Biological	Group P6: Placebo

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 Weeks 0, 16, 32, 48, 64
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 Weeks 0, 16, 32, 48, 64
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 Weeks 0, 16, 32, 48, 64
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)
Time frame: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Chemistry and Hematology Laboratory Measures - Creatinine
Time frame: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Chemistry and Hematology Laboratory Measures - Hemoglobin
Time frame: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
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
Time frame: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Chemistry and Hematology Laboratory Measures - Platelets, White Blood Cells (WBC)
Time frame: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Number of Lab Grade >= 1 for Alanine Aminotransferase (ALT), Creatinine, Hemoglobin, Lymphocyte Count, Neutrophil Count, Platelets, White Blood Cells (WBC).
Time frame: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728
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
VRC07523LS Serum Concentrations
Time frame: Target Visit Days 0, 3, 6, 28, 56, 84, 112, 168, 224, 280, 336, 392, 448, 504, 560, 616, 672, 728, 784 (i.e., visit numbers 2 through 20)
VRC07523LS serum concentrations measured in healthy human subjects after up to five administrations of the study product via the IV, SC or IM routes at various doses. Serum concentrations between the first and second study product administrations (Target Visit Day 0-112) were measured using ELISA assay in all enrolled participants. Serum concentrations after the second study product administrations (Target Visit Day 168-784) were measured using BAMA (LUMINEX) assay in a subset of participants enrolled in each treatment group and all particiants in plocebo group. serum concentrations below the lower limit of quantification (LLoQ) were replaced by half the LLoQ. Thus, concentrations below the LLoQ when measured by the ELISA assay were replaced by 0.5 ug/ml and concentrations below the LLoQ when measured by the BAMA assay were replaced by 0.02285 ug/ml.

2 secondary outcomes

Occurrence of Antidrug Antibodies (ADA)
Time frame: Day 0, 6, 112, 224, 448
Magnitude and Breadth of Neutralizing Antibody Responses Against Autologous Viral Isolates as Assessed by Area Under the Magnitude-breadth Curves 8, 72, 88 Weeks After the First Study Product Administration.
Time frame: Weeks 8, 72, and 88 following the first study product administration

Results and safety

Results posted to the registry on 21 Mar 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
Group 1: Vaccine	19	13
Group 2: Vaccine	19	16
Group 3: Vaccine	21	16
Group 4: Vaccine	21	14
Group 5: Vaccine	20	14
Group 6: Vaccine	21	14
Group 7: Placebo	3	3

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 Weeks 0, 16, 32, 48, 64. Count of participants. Unit: Participants

Measure	Group 1: Vaccine n = 19	Group 2: Vaccine n = 19	Group 3: Vaccine n = 21	Group 4: Vaccine n = 21	Group 5: Vaccine n = 20	Group 6: Vaccine n = 21	Group 7: Placebo n = 3
None	12	11	15	8	5	7	2
Mild	6	8	5	11	15	13	1
Moderate	1	0	1	2	0	1	0
Severe	0	0	0	0	0	0	0
Potentially Life-threatening	0	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 Weeks 0, 16, 32, 48, 64. Count of participants. Unit: Participants

Measure	Group 1: Vaccine n = 19	Group 2: Vaccine n = 19	Group 3: Vaccine n = 21	Group 4: Vaccine n = 21	Group 5: Vaccine n = 20	Group 6: Vaccine n = 21	Group 7: Placebo n = 3
Erythema/Redness: None	14	15	16	7	7	19	3
Erythema/Redness: Not gradable	3	4	3	2	3	0	0
Erythema/Redness: Gr 1: 2.5 - less than 5cm dim.	0	0	1	2	2	0	0
Erythema/Redness: Gr 1: 6.25 - less than 25cm^2 area	1	0	0	4	3	2	0
Erythema/Redness: Gr 2: 5 - less than 10cm dim.	0	0	1	2	5	0	0
Erythema/Redness: Gr 2: 25 - less than 100cm^2 area	1	0	0	1	0	0	0
Erythema/Redness: Gr 3: >= 10cm dim.	0	0	0	1	0	0	0
Erythema/Redness: Gr 3: >= 100cm^2 area	0	0	0	2	0	0	0

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

Time frame: Measured through 3 days after each vaccine dose at Weeks 0, 16, 32, 48, 64. Count of participants. Unit: Participants

Measure	Group 1: Vaccine n = 19	Group 2: Vaccine n = 19	Group 3: Vaccine n = 21	Group 4: Vaccine n = 21	Group 5: Vaccine n = 20	Group 6: Vaccine n = 21	Group 7: Placebo n = 3
Malaise and/or fatigue: None	10	10	7	12	13	14	1
Malaise and/or fatigue: Mild	6	5	7	6	6	4	2
Malaise and/or fatigue: Moderate	3	4	5	3	1	3	0
Malaise and/or fatigue: Severe	0	0	2	0	0	0	0
Malaise and/or fatigue: Potentially Life-threatening	0	0	0	0	0	0	0
Myalgia: None	18	16	14	18	17	17	3
Myalgia: Mild	1	3	2	2	3	4	0
Myalgia: Moderate	0	0	4	1	0	0	0

Primary outcome: Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT)

Time frame: Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728. Median (Inter-Quartile Range). Unit: U/L

Measure	Group 1: Vaccine n = 19	Group 2: Vaccine n = 19	Group 3: Vaccine n = 21	Group 4: Vaccine n = 21	Group 5: Vaccine n = 20	Group 6: Vaccine n = 21	Group 7: Placebo n = 3
ALT (SGPT) (U/L)- Screening	16 (11 to 21)	16 (13 to 21)	16 (12 to 21)	14 (12 to 17)	18 (10.5 to 20)	13 (13 to 20)	13 (12 to 16)
ALT (SGPT) (U/L)- 0/Enrollment	14 (9 to 17)	16 (12 to 17)	19 (12 to 22)	13.5 (10 to 21)	13 (11.5 to 21.5)	12 (10 to 20)	17 (15 to 33)
ALT (SGPT) (U/L)- 56	15 (10 to 23)	16 (12 to 21)	15 (12.5 to 23)	13 (10 to 21)	15 (11 to 24)	13 (11 to 23)	31 (13 to 114)
ALT (SGPT) (U/L)- 112	16 (11 to 18)	20 (13 to 23)	13 (11.5 to 20.5)	12 (12 to 18)	16 (14 to 25)	14 (10.5 to 20.5)	19 (16 to 42)
ALT (SGPT) (U/L)- 168	13.5 (11 to 21)	14.5 (13 to 23)	15 (10 to 21)	14 (10 to 24.5)	16.5 (14 to 28)	15 (12 to 23)	19 (13 to 38)
ALT (SGPT) (U/L)- 224	18 (10.5 to 22.5)	17 (13 to 21)	15.5 (11.5 to 19.5)	13 (11 to 25)	14 (12 to 20)	14.5 (12.5 to 19)	17 (13 to 39)
ALT (SGPT) (U/L)- 280	16 (10 to 29)	18 (14 to 25)	15 (13 to 20)	15 (11 to 23)	17 (11 to 22)	14 (11 to 23)	18 (14 to 22)
ALT (SGPT) (U/L)- 336	15 (11 to 23)	17 (15 to 18)	14.5 (11 to 22)	15 (11 to 20)	16 (11.5 to 20)

2 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) the Week 112 visit (v20.0). The Solicited AE assessment were collected through 3 full days after each vaccination (vaccinations were given at weeks 0, 16, 32, 48 and 64).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1: Vaccine	1 of 19 (5.3%)	14 of 19 (73.7%)	0 of 19
Group 2: Vaccine	1 of 19 (5.3%)	16 of 19 (84.2%)	0 of 19
Group 3: Vaccine	0 of 21 (0%)	14 of 21 (66.7%)	0 of 21
Group 4: Vaccine	1 of 21 (4.8%)	18 of 21 (85.7%)	0 of 21
Group 5: Vaccine	0 of 20 (0%)	16 of 20 (80%)	0 of 20
Group 6: Vaccine	0 of 21 (0%)	17 of 21 (81%)	0 of 21
Group 7: Placebo	0 of 3 (0%)	3 of 3 (100%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38913710Walsh SR, Gay CL, Karuna ST, Hyrien O, Skalland T, Mayer KH, Sobieszczyk ME, Baden LR, Goepfert PA, Del Rio C, Pantaleo G, Andrew P, Karg C, He Z, Lu H, Paez CA, Baumblatt JAG, Polakowski LL, Chege W, Anderson MA, Janto S, Han X, Huang Y, Dumond J, Ackerman ME, McDermott AB, Flach B, Piwowar-Manning E, Seaton K, Tomaras GD, Montefiori DC, Gama L, Mascola JR; HVTN 127/HPTN 087 Study Team. Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial. PLoS Med. 2024 Jun 24;21(6):e1004329. doi: 10.1371/journal.pmed.1004329. eCollection 2024 Jun.

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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.

Stephen Walsh study chair

Brigham and Women's Hospital

Cynthia Gay study chair

University of North Carolina, Chapel Hill

7 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing VRC07-523LS in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in 2 countries.

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 38 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 5 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Switzerland. 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. Some participants in this study may receive a placebo. 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 21 Mar 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 Weeks 0, 16, 32, 48, 64). 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 NCT03387150, 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 5 Apr 2023.