HIV PreventionPhase 1NCT03015181

VRC 605: Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously or Subcutaneously to Healthy Adults

A Phase 1 study testing VRC-HIVMAB075-00-AB in people with HIV Prevention, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

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

Official record

Search all trials

Trial summary

Background: Human immunodeficiency virus (HIV) is a global health threat. The body uses antibodies to fight infection. VRC07-523LS is an antibody directed against HIV. It may be used to prevent mother-to-child transmission of HIV. It may also prevent sexual transmission of HIV and treat HIV-1 infected people. Read more about this study

Who is it for?: Ages 18 to 50 years
Conditions the study is for: HIV Prevention
What is being tested?: VRC-HIVMAB075-00-AB
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 1 siteUnited States
Study dates: 21 Feb 2017to 10 Jul 2018
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
No healthy volunteers
Adult

Who may be able to join

A volunteer must meet all of the following criteria:
Able and willing to complete the informed consent process.
18 to 50 years of age.
Based on history and examination, must be in good general health and without history of any of the conditions listed in the exclusion criteria.
Willing to have blood samples collected, stored indefinitely, and used for research purposes.
Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.

Show all 18Show fewer

Willing to adhere to reduced risk sexual behavior during study participation.
Screening laboratory values within 84 days prior to enrollment must meet the following criteria:
White Blood Cell (WBC) 2,500-12,000/mm^3.
WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
Platelets = 125,000 - 400,000/mm^3.
Hemoglobin within institutional normal range.
Creatinine less than or equal to 1.1 x upper limit of normal (ULN).
Alanine aminotransferase (ALT) less than or equal to 1.25 x ULN.
Negative for HIV infection by the FDA approved method of detection.
Female-Specific Criteria:
If a woman is of reproductive potential and sexually active with a male partner, then she agrees to use an effective means of birth control from the time of study enrollment until the last study visit, or to be monogamous with a partner who has had a vasectomy.
Negative Beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential.

Who cannot join

A volunteer will be excluded if one or more of the following conditions apply:
Previous receipt of licensed or investigational monoclonal antibody.
Weight >115 kg.
Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the study.
Hypertension that is not well controlled.
Woman who is breast-feeding, or planning to become pregnant during the study participation.
Receipt of any investigational study agent within 28 days prior to enrollment.
Any other chronic or clinically significant medical condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer, including but not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of: drug or alcohol abuse, asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: VRC 605: A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously or Subcutaneously to Healthy Adults

Background:

Human immunodeficiency virus (HIV) is a global health threat. The body uses antibodies to fight infection. VRC07-523LS is an antibody directed against HIV. It may be used to prevent mother-to-child transmission of HIV. It may also prevent sexual transmission of HIV and treat HIV-1 infected people.

Objective:

To test the safety, tolerability, dose, and pharmacokinetics of VRC07-523LS in healthy adults.

Eligibility:

Healthy people ages 18-50

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Participants will be assigned to 1 of 7 groups:

Groups 1-5 will get the drug at 1 visit and then be observed for 24 weeks.

Groups 6 and 7 will get the drug at 1 visit every 12 weeks, for a total of 3 doses over 48 weeks.

Participants will get the drug in 1 of 2 ways:

Infusion into a vein over at least 30 minutes. Participants will have blood tests 1, 3, and 6 hours after the infusion. They will have 1-3 visits during that week. Those in Group 7 will have 4-5 visits in the week after their second and third doses.

Injection into the fatty tissue under the skin. Participants will have blood tests before the injection. They will have 1-3 visits during that week. Those in Group 6 will have 4-5 visits after the second and third doses.

Visits include:

Physical exam

Blood and urine tests

Optional oral swabs to collect saliva

Participants will keep a diary of their temperature and symptoms for 3 days after each dose.

Read the detailed description

This is the first study of the VRC-HIVMAB075-00-AB (VRC07-523LS) monoclonal antibody (MAb) in healthy adults. It is a phase 1, dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics of VRC07-523LS. The hypothesis is that VRC07-523LS will be safe for administration to healthy adults by the intravenous (IV) and subcutaneous (SC) routes.

Healthy adults 18-50 years of age will be enrolled. There are 4 open-label, dose escalations of VRC07-523LS from 1 mg/kg IV to 40 mg/kg IV, 1 route escalation from IV to SC, and 2 open-label groups to assess repeat dosing. Groups 1-5 are expected to include 3 subjects and Groups 6-7 are expected to enroll 5 subjects. Subjects will be followed for 24 weeks after the last study product administration.

Conditions: HIV Prevention
Being tested: VRC-HIVMAB075-00-AB
Keywords: Broadly Neutralizing, HIV Prevention, Anti-Drug Antibody, HIV-1, Immune Response

What participants receive

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

VRC-HIVMAB075-00-ABBiological
Also called VRC07-523LS
VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Study groups in NCT03015181
Study group	Role	What they receive
Group 1: 1 mg/kg IV Single Dose	Experimental	Group 1 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 1 mg/kg. Receives: Biological: VRC-HIVMAB075-00-AB
Group 2: 5 mg/kg IV Single Dose	Experimental	Group 2 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 5 mg/kg. Receives: Biological: VRC-HIVMAB075-00-AB
Group 3: 5 mg/kg SC Single Dose	Experimental	Group 3 subjects received a single SC injection of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 5 mg/kg. Receives: Biological: VRC-HIVMAB075-00-AB
Group 4: 20 mg/kg IV Single Dose	Experimental	Group 4 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 20 mg/kg. Receives: Biological: VRC-HIVMAB075-00-AB
Group 5: 40 mg/kg IV Single Dose	Experimental	Group 5 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 40 mg/kg. Receives: Biological: VRC-HIVMAB075-00-AB
Group 6: 5 mg/kg SC Multiple Doses	Experimental	Group 6 subjects received a SC injection of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0, Week 12 and Week 24 at a dose of 5 mg/kg. Receives: Biological: VRC-HIVMAB075-00-AB
Group 7: 20 mg/kg IV Multiple Doses	Experimental	Group 7 subjects received an IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0, Week 12 and Week 24 at a dose of 20 mg/kg. Receives: Biological: VRC-HIVMAB075-00-AB

What is being measured

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

Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Any Product Administration
Subjects recorded 3-day systemic symptoms in a diary after each study product administration. Solicited systemic symptoms include: unusually tired/feeling unwell, muscles aches, headache, chills, nausea, temperature and joint pain. Subjects recorded highest measured temperature daily. Clinicians reviewed the diary with the subject and collected resolution information for any symptoms that were not resolved within 3 days. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects reporting any systemic symptom at the worst severity. Solicited reactogenicity was recorded without an attribution assessment. Grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.0.
Measured: 3 days after each product administration
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration
Local symptoms assessed and recorded by the clinicians. Solicited local symptoms include pain/tenderness, swelling, redness, bruising, and pruritus (itchiness) at the product administration site. Clinicians assessed the study product administration site for local symptoms on the day of product administration after completion of the administration and on Days 1, 2 and 7 post administration. Subjects were counted once for each symptom at the worst severity if they experienced the symptom at any severity during the reporting period. If symptoms were experienced, clinicians collected resolution information for any symptom that was not resolved within 7 days. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom at the worst severity. Solicited reactogenicity recorded without an attribution assessment. If symptoms were reported, grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.0.
Measured: 7 days after each product administration
Number of Subjects Reporting 1 or More Unsolicited Non-Serious Adverse Events
Unsolicited adverse events (AEs) collected during the period from study product administration at Day 0 through 56 days after the last product administration. After the indicated time period through the last expected study visit at 24 weeks after the last product administration, only new chronic medical conditions collected as unsolicited AEs. The number reported is the number of subjects who experienced at least one AE in the reporting period. A subject with multiple experiences of the same event is counted once using the event of worst severity.
Measured: Through 24 weeks after the last product administration
Number of Subjects Reporting Serious Adverse Events
Serious adverse events (SAEs) collected during the period from study product administration at Day 0 through 24 weeks after the last product administration.
Measured: Through 24 weeks after the last product administration

Secondary outcomes (12)

Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Single Dose Groups
Cmax is the peak serum concentration that VRC07-523LS achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group.
Serum was collected at the following time points:
Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4, 8, 12, 16, 20, and 24 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4, 8, 12, 16, 20, and 24 post injection
Measured: Up to 24 weeks post product administration
Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Multiple Dose Groups
Cmax is the peak serum concentration that VRC07-523LS achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group.
Serum was collected at the following time points for Groups 6 and 7 after Dose 1 and Dose 3:
Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2, 4 and 8 post injection; Group 6, Dose 3: Pre-injection (Week 24) and 72 hours post injection, followed by Weeks 25-28 and every 4 weeks up to 48 weeks post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hrs post infusion, followed by Weeks 1, 2, 4 and 8 post infusion; Group 7, Dose 3: Pre-infusion (Week 24), end of infusion and 1 hour post infusion followed by Weeks 25-28 and every 4 weeks up to 48 weeks post infusion
Measured: Through 24 weeks after the last product administration
Time to Reach Maximum Observed Serum Concentration (Tmax) of VRC07-523LS
Tmax is the time it takes to reach Cmax of VRC07-523LS after it has been administered; it is determined based on the summary PK curve for each study group
Serum was collected at the following time points:
Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4, 8, 12, 16, 20, and 24 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4, 8, 12, 16, 20, and 24 post injection; Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2, 4 and 8 post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1, 2, 4 and 8 post infusion
Measured: Through 24 weeks after the last product administration for Groups 1-5 and through 8 weeks after the last product administration for Groups 6 and 7
4 Week Mean Serum Concentration of VRC07-523LS
The mean of individual subject VRC07-523LS serum concentrations by administered dose group
Measured: Week 4 post product administration
12 Week Mean Serum Concentration of VRC07-523LS: Single Dose Groups
The mean of individual subject VRC07-523LS serum concentrations by administered dose group
Measured: Week 12 post product administration
12 Week Mean Serum Concentration of VRC07-523LS: Multiple Dose Groups
The mean of individual subject VRC07-523LS serum concentrations by administered dose group
Measured: Up to 12 weeks after each product administration
Area Under the Curve (AUC(0-inf)): Single Dose Groups
The total area under the curve (AUC(inf)) was taken as the sum of the observed AUC up to the final concentration (AUC(obs)) plus the AUC after the final concentration (AUC(Clast-inf)) where AUC(Clast-inf) was estimated as Clast/lz.
Serum was collected at the following time points:
Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4, 8, 12, 16, 20, and 24 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4, 8, 12, 16, 20, and 24 post injection
Measured: Administration (0h) to 24 weeks post product administration
Area Under the Curve (AUC0-84D): Multiple Dose Groups
The AUC0-84D represents the total drug exposure in 84 days after VRC07-523LS administration; it is determined based on the summary PK curve for each group.
Serum was collected at the following time points for Groups 6 and 7 after Dose 1 and Dose 3:
Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2, 4 and 8 post injection; Group 6, Dose 3: Pre-injection (Week 24) and 72 hours post injection, followed by Weeks 25-28 and every 4 weeks up to 48 weeks post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hrs post infusion, followed by Weeks 1, 2, 4 and 8 post infusion; Group 7, Dose 3: Pre-infusion (Week 24), end of infusion and 1 hour post infusion followed by Weeks 25-28 and every 4 weeks up to 48 weeks post infusion
Measured: Administration (0h) up to 84 days after each product administration
VRC07-523LS Clearance Rate
Rate of VRC07-523LS elimination divided by the plasma VRC07-523LS concentration; determined based on the summary PK curve for each study group.
Serum was collected at the following time points:
Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4 post injection; Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2 and 4 post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1, 2 and 4 post infusion
Measured: Administration (0h) to 28 days post product administration
Overall IV Half-life (T1/2) of VRC07-523LS
Half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.
Serum was collected at the following time points:
Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4 and 8 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4 and 8 post injection; Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2, 4 and 8 post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1, 2, 4 and 8 post infusion
Measured: Administration (0h) to 56 days post product administration
Number of Single Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS
Serum samples collected 4 weeks and 8 weeks after VRC07-523LS administration
Measured: Weeks 4 and 8 post product administration
Number of Multiple Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS
Serum samples collected 4 weeks, 28 weeks and 32 weeks after VRC07-523LS administration
Measured: Weeks 4, 28 and 32 after the first product administration

Timeline

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

21 Feb 201710 Jul 2018

First posted9 Jan 2017 (estimated)
Study start21 Feb 2017
Primary completion10 Jul 2018
Study completion10 Jul 2018

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 (3)Papers the sponsor has linked to this study.
Other trials for HIV PreventionStudies 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: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03015181
Sponsor's protocol ID: 170030
Other IDs: 17-I-0030
Status last verified: Oct 2020
First submitted: 6 Jan 2017
Last updated: 26 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Rudicell RS, Kwon YD, Ko SY, Pegu A, Louder MK, Georgiev IS, Wu X, Zhu J, Boyington JC, Chen X, Shi W, Yang ZY, Doria-Rose NA, McKee K, O'Dell S, Schmidt SD, Chuang GY, Druz A, Soto C, Yang Y, Zhang B, Zhou T, Todd JP, Lloyd KE, Eudailey J, Roberts KE, Donald BR, Bailer RT, Ledgerwood J; NISC Comparative Sequencing Program; Mullikin JC, Shapiro L, Koup RA, Graham BS, Nason MC, Connors M, Haynes BF, Rao SS, Roederer M, Kwong PD, Mascola JR, Nabel GJ. Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. J Virol. 2014 Nov;88(21):12669-82. doi: 10.1128/JVI.02213-14. Epub 2014 Aug 20.
PubMed 25142607
Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ, Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010 Aug 13;329(5993):856-61. doi: 10.1126/science.1187659. Epub 2010 Jul 8.
PubMed 20616233
Gaudinski MR, Houser KV, Doria-Rose NA, Chen GL, Rothwell RSS, Berkowitz N, Costner P, Holman LA, Gordon IJ, Hendel CS, Kaltovich F, Conan-Cibotti M, Gomez Lorenzo M, Carter C, Sitar S, Carlton K, Gall J, Laurencot C, Lin BC, Bailer RT, McDermott AB, Ko SY, Pegu A, Kwon YD, Kwong PD, Namboodiri AM, Pandey JP, Schwartz R, Arnold F, Hu Z, Zhang L, Huang Y, Koup RA, Capparelli EV, Graham BS, Mascola JR, Ledgerwood JE; VRC 605 study team. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. Lancet HIV. 2019 Oct;6(10):e667-e679. doi: 10.1016/S2352-3018(19)30181-X. Epub 2019 Aug 28.
PubMed 31473167

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?

See locations

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
HIV/STI/HCV Testing and Overdose Prevention Among Survivors of Sex Trafficking
HIV Testing, STI
Not yet recruiting
HC-HMP: Healthy Choices Implementation Trial
Alcohol Drinking, HIV Infections
Not yet recruitingPhase 4
NOTRE: Optimizing Long-Acting Pre-Exposure Prophylaxis and Medications for Opioid Use Disorder Interventions in Carceral Settings
HIV Infections, Opioid Use Disorder
Active, not recruitingPhase 3
Long-term Follow-up of Long-acting Cabotegravir (CAB LA) for PrEP (Pre-exposure Prophylaxis) in Participants at Risk of Acquiring HIV (Human Immunodeficiency Virus)
HIV Infections

All HIV Prevention trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: VRC 605: A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously or Subcutaneously to Healthy Adults
ClinicalTrials.gov ID: NCT03015181
Acronym / sponsor ID: 170030
Conditions: HIV Prevention
Keywords: Broadly Neutralizing, HIV Prevention, Anti-Drug Antibody, HIV-1, Immune Response
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: 21 Feb 2017 (actual)
Primary completion: 10 Jul 2018 (actual)
Study completion: 10 Jul 2018 (actual)
First posted: 9 Jan 2017 (estimated)
Results: Posted 11 Jul 2019

Clinical summary

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

Background:

Objective:

To test the safety, tolerability, dose, and pharmacokinetics of VRC07-523LS in healthy adults.

Eligibility:

Healthy people ages 18-50

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Participants will be assigned to 1 of 7 groups:

Groups 1-5 will get the drug at 1 visit and then be observed for 24 weeks.

Groups 6 and 7 will get the drug at 1 visit every 12 weeks, for a total of 3 doses over 48 weeks.

Participants will get the drug in 1 of 2 ways:

Visits include:

Physical exam

Blood and urine tests

Optional oral swabs to collect saliva

Participants will keep a diary of their temperature and symptoms for 3 days after each dose.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 7

Arm	Type	Receives
Group 1: 1 mg/kg IV Single Dose	Experimental	Biological: VRC-HIVMAB075-00-ABGroup 1 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 1 mg/kg.
Group 2: 5 mg/kg IV Single Dose	Experimental	Biological: VRC-HIVMAB075-00-ABGroup 2 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 5 mg/kg.
Group 3: 5 mg/kg SC Single Dose	Experimental	Biological: VRC-HIVMAB075-00-ABGroup 3 subjects received a single SC injection of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 5 mg/kg.
Group 4: 20 mg/kg IV Single Dose	Experimental	Biological: VRC-HIVMAB075-00-ABGroup 4 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 20 mg/kg.
Group 5: 40 mg/kg IV Single Dose	Experimental	Biological: VRC-HIVMAB075-00-ABGroup 5 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 40 mg/kg.
Group 6: 5 mg/kg SC Multiple Doses	Experimental	Biological: VRC-HIVMAB075-00-ABGroup 6 subjects received a SC injection of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0, Week 12 and Week 24 at a dose of 5 mg/kg.
Group 7: 20 mg/kg IV Multiple Doses	Experimental	Biological: VRC-HIVMAB075-00-ABGroup 7 subjects received an IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0, Week 12 and Week 24 at a dose of 20 mg/kg.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (18 listed)

Able and willing to complete the informed consent process.
18 to 50 years of age.
Based on history and examination, must be in good general health and without history of any of the conditions listed in the exclusion criteria.
Willing to have blood samples collected, stored indefinitely, and used for research purposes.
Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.

Key exclusion criteria (8 listed)

Previous receipt of licensed or investigational monoclonal antibody.
Weight >115 kg.
Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the study.
Hypertension that is not well controlled.
Woman who is breast-feeding, or planning to become pregnant during the study participation.

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
VRC-HIVMAB075-00-ABAlso: VRC07-523LSVRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.	Biological	Group 1: 1 mg/kg IV Single Dose, Group 2: 5 mg/kg IV Single Dose, Group 3: 5 mg/kg SC Single Dose, Group 4: 20 mg/kg IV Single Dose, Group 5: 40 mg/kg IV Single Dose, Group 6: 5 mg/kg SC Multiple Doses, Group 7: 20 mg/kg IV Multiple Doses

Primary outcome

Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Any Product Administration
Time frame: 3 days after each product administration
Subjects recorded 3-day systemic symptoms in a diary after each study product administration. Solicited systemic symptoms include: unusually tired/feeling unwell, muscles aches, headache, chills, nausea, temperature and joint pain. Subjects recorded highest measured temperature daily. Clinicians reviewed the diary with the subject and collected resolution information for any symptoms that were not resolved within 3 days. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects reporting any systemic symptom at the worst severity. Solicited reactogenicity was recorded without an attribution assessment. Grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.0.
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration
Time frame: 7 days after each product administration
Local symptoms assessed and recorded by the clinicians. Solicited local symptoms include pain/tenderness, swelling, redness, bruising, and pruritus (itchiness) at the product administration site. Clinicians assessed the study product administration site for local symptoms on the day of product administration after completion of the administration and on Days 1, 2 and 7 post administration. Subjects were counted once for each symptom at the worst severity if they experienced the symptom at any severity during the reporting period. If symptoms were experienced, clinicians collected resolution information for any symptom that was not resolved within 7 days. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom at the worst severity. Solicited reactogenicity recorded without an attribution assessment. If symptoms were reported, grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.0.
Number of Subjects Reporting 1 or More Unsolicited Non-Serious Adverse Events
Time frame: Through 24 weeks after the last product administration
Unsolicited adverse events (AEs) collected during the period from study product administration at Day 0 through 56 days after the last product administration. After the indicated time period through the last expected study visit at 24 weeks after the last product administration, only new chronic medical conditions collected as unsolicited AEs. The number reported is the number of subjects who experienced at least one AE in the reporting period. A subject with multiple experiences of the same event is counted once using the event of worst severity.
Number of Subjects Reporting Serious Adverse Events
Time frame: Through 24 weeks after the last product administration
Serious adverse events (SAEs) collected during the period from study product administration at Day 0 through 24 weeks after the last product administration.

12 secondary outcomes

Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Single Dose Groups
Time frame: Up to 24 weeks post product administration
Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Multiple Dose Groups
Time frame: Through 24 weeks after the last product administration
Time to Reach Maximum Observed Serum Concentration (Tmax) of VRC07-523LS
Time frame: Through 24 weeks after the last product administration for Groups 1-5 and through 8 weeks after the last product administration for Groups 6 and 7
4 Week Mean Serum Concentration of VRC07-523LS
Time frame: Week 4 post product administration
12 Week Mean Serum Concentration of VRC07-523LS: Single Dose Groups
Time frame: Week 12 post product administration
12 Week Mean Serum Concentration of VRC07-523LS: Multiple Dose Groups
Time frame: Up to 12 weeks after each product administration
Area Under the Curve (AUC(0-inf)): Single Dose Groups
Time frame: Administration (0h) to 24 weeks post product administration
Area Under the Curve (AUC0-84D): Multiple Dose Groups
Time frame: Administration (0h) up to 84 days after each product administration
VRC07-523LS Clearance Rate
Time frame: Administration (0h) to 28 days post product administration
Overall IV Half-life (T1/2) of VRC07-523LS
Time frame: Administration (0h) to 56 days post product administration
Number of Single Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS
Time frame: Weeks 4 and 8 post product administration
Number of Multiple Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS
Time frame: Weeks 4, 28 and 32 after the first product administration

Results and safety

Results posted to the registry on 11 Jul 2019, 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: 1 mg/kg IV Single Dose	4	3
Group 2: 5 mg/kg IV Single Dose	3	3
Group 3: 5 mg/kg SC Single Dose	3	3
Group 4: 20 mg/kg IV Single Dose	3	3
Group 5: 40 mg/kg IV Single Dose	3	3
Group 6: 5 mg/kg SC Multiple Doses	5	4
Group 7: 20 mg/kg IV Multiple Doses	5	4

Primary outcome: Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Any Product Administration

Time frame: 3 days after each product administration. Count of participants. Unit: Participants

Measure	Group 1: 1 mg/kg IV Single Dose n = 3	Group 2: 5 mg/kg IV Single Dose n = 3	Group 4: 20 mg/kg IV Single Dose n = 3	Group 5: 40 mg/kg IV Single Dose n = 3	Group 7: 20 mg/kg IV Multiple Doses: Dose 1 n = 5	Group 7: 20 mg/kg IV Multiple Doses: Dose 2 n = 4	Group 7: 20 mg/kg IV Multiple Doses: Dose 3 n = 4	Overall IV Groups n = 17	Group 3: 5 mg/kg SC Single Dose n = 3	Group 6: 5 mg/kg SC Multiple Doses: Dose 1 n = 5	Group 6: 5 mg/kg SC Multiple Doses: Dose 2 n = 4	Group 6: 5 mg/kg SC Multiple Doses: Dose 3 n = 4	Overall SC Groups n = 8
Malaise: None	3	3	3	2	3	3	3	14	3	2	4	4	5
Malaise: Mild	0	0	0	0	2	1	1	2	0	3	0	0	3
Malaise: Moderate	0	0	0	1	0	0	0	1	0	0	0	0	0
Myalgia: None	3	2	3	2	4	3	3	14	3	3	4	4	6
Myalgia: Mild	0	1	0	1	1	1	0	2	0	2	0	0	2
Myalgia: Moderate	0	0	0	0	0	0	1	1	0	0	0	0	0
Headache: None	3	3	3	2	4	3	4	15	3	3	3	4	5
Headache: Mild	0	0	0	1	1	1	0	2	0	2	1	0	3

Population analysed: Subjects who received VRC07-523LS (N=25), where "N" signifies number of subjects analyzed for this outcome measure. Groups 1, 2, 4, 5 and 7 are IV administration groups and Groups 3 and 6 are SC administration groups, with Groups 6 and 7 receiving multiple doses.

Primary outcome: Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration

Time frame: 7 days after each product administration. Count of participants. Unit: Participants

Measure	Group 1: 1 mg/kg IV Single Dose n = 3	Group 2: 5 mg/kg IV Single Dose n = 3	Group 4: 20 mg/kg IV Single Dose n = 3	Group 5: 40 mg/kg IV Single Dose n = 3	Group 7: 20 mg/kg IV Multiple Doses: Dose 1 n = 5	Group 7: 20 mg/kg IV Multiple Doses: Dose 2 n = 4	Group 7: 20 mg/kg IV Multiple Doses: Dose 3 n = 4	Overall IV Groups n = 17	Group 3: 5 mg/kg SC Single Dose n = 3	Group 6: 5 mg/kg SC Multiple Doses: Dose 1 n = 5	Group 6: 5 mg/kg SC Multiple Doses: Dose 2 n = 4	Group 6: 5 mg/kg SC Multiple Doses: Dose 3 n = 4	Overall SC Groups n = 8
Pain/Tenderness: None	3	3	2	3	5	4	4	16	2	2	1	2	4
Pain/Tenderness: Mild	0	0	1	0	0	0	0	1	1	3	3	2	4
Pain/Tenderness: Moderate	0	0	0	0	0	0	0	0	0	0	0	0	0
Bruising: None	3	3	3	3	4	4	4	16	3	5	4	4	8
Bruising: Mild	0	0	0	0	1	0	0	1	0

Primary outcome: Number of Subjects Reporting 1 or More Unsolicited Non-Serious Adverse Events

Time frame: Through 24 weeks after the last product administration. Count of participants. Unit: Participants

Measure	Group 1: 1 mg/kg IV Single Dose n = 3	Group 2: 5 mg/kg IV Single Dose n = 3	Group 3: 5 mg/kg SC Single Dose n = 3	Group 4: 20 mg/kg IV Single Dose n = 3	Group 5: 40 mg/kg IV Single Dose n = 3	Group 6: 5 mg/kg SC Multiple Doses n = 5	Group 7: 20 mg/kg IV Multiple Doses n = 5	Overall n = 25
Related to study product	0	0	0	0	2	0	2	4
Unrelated to study product	2	1	1	0	0	5	3	12

Population analysed: Subjects who received VRC07-523LS (N=25), where "N" signifies number of subjects analyzed for this outcome measure.

Primary outcome: Number of Subjects Reporting Serious Adverse Events

Time frame: Through 24 weeks after the last product administration. Count of participants. Unit: Participants

Measure	Group 1: 1 mg/kg IV Single Dose n = 3	Group 2: 5 mg/kg IV Single Dose n = 3	Group 3: 5 mg/kg SC Single Dose n = 3	Group 4: 20 mg/kg IV Single Dose n = 3	Group 5: 40 mg/kg IV Single Dose n = 3	Group 6: 5 mg/kg SC Multiple Doses n = 5	Group 7: 20 mg/kg IV Multiple Doses n = 5	Overall n = 25
Related to study product	0	0	0	0	0	0	0	0
Unrelated to study product	0	0	0	0	0	0	0	0

Population analysed: Subjects who received VRC07-523LS (N=25), where "N" signifies number of subjects analyzed for this outcome measure.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited adverse events (AEs) included systemic AEs reported by subjects at the worst severity through 3 days post any product administration; and local administration site AEs reported for subjects at the worst severity through 7 days post any product administration. Unsolicited AEs were reported from the date of product administration through 56 days thereafter, and new chronic medical conditions and SAEs with onset any time following the date of last product administration through 24 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1: 1 mg/kg IV Single Dose	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Group 2: 5 mg/kg IV Single Dose	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Group 4: 20 mg/kg IV Single Dose	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Group 5: 40 mg/kg IV Single Dose	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Group 7: 20 mg/kg IV Multiple Doses	0 of 5 (0%)	5 of 5 (100%)	0 of 5
Group 3: 5 mg/kg SC Single Dose	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Group 6: 5 mg/kg SC Multiple Doses	0 of 5 (0%)	5 of 5 (100%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25142607Rudicell RS, Kwon YD, Ko SY, Pegu A, Louder MK, Georgiev IS, Wu X, Zhu J, Boyington JC, Chen X, Shi W, Yang ZY, Doria-Rose NA, McKee K, O'Dell S, Schmidt SD, Chuang GY, Druz A, Soto C, Yang Y, Zhang B, Zhou T, Todd JP, Lloyd KE, Eudailey J, Roberts KE, Donald BR, Bailer RT, Ledgerwood J; NISC Comparative Sequencing Program; Mullikin JC, Shapiro L, Koup RA, Graham BS, Nason MC, Connors M, Haynes BF, Rao SS, Roederer M, Kwong PD, Mascola JR, Nabel GJ. Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. J Virol. 2014 Nov;88(21):12669-82. doi: 10.1128/JVI.02213-14. Epub 2014 Aug 20.
Background: PubMed 20616233Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ, Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010 Aug 13;329(5993):856-61. doi: 10.1126/science.1187659. Epub 2010 Jul 8.
Results publication: PubMed 31473167Gaudinski MR, Houser KV, Doria-Rose NA, Chen GL, Rothwell RSS, Berkowitz N, Costner P, Holman LA, Gordon IJ, Hendel CS, Kaltovich F, Conan-Cibotti M, Gomez Lorenzo M, Carter C, Sitar S, Carlton K, Gall J, Laurencot C, Lin BC, Bailer RT, McDermott AB, Ko SY, Pegu A, Kwon YD, Kwong PD, Namboodiri AM, Pandey JP, Schwartz R, Arnold F, Hu Z, Zhang L, Huang Y, Koup RA, Capparelli EV, Graham BS, Mascola JR, Ledgerwood JE; VRC 605 study team. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. Lancet HIV. 2019 Oct;6(10):e667-e679. doi: 10.1016/S2352-3018(19)30181-X. Epub 2019 Aug 28.
Individual participant dataSharing planned: No

Related trials for HIV Prevention

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
HIV/STI/HCV Testing and Overdose Prevention Among Survivors of Sex Trafficking
HIV Testing, STI
Not yet recruiting
HC-HMP: Healthy Choices Implementation Trial
Alcohol Drinking, HIV Infections
Not yet recruitingPhase 4
NOTRE: Optimizing Long-Acting Pre-Exposure Prophylaxis and Medications for Opioid Use Disorder Interventions in Carceral Settings
HIV Infections, Opioid Use Disorder
Active, not recruitingPhase 3
Long-term Follow-up of Long-acting Cabotegravir (CAB LA) for PrEP (Pre-exposure Prophylaxis) in Participants at Risk of Acquiring HIV (Human Immunodeficiency Virus)
HIV Infections

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.

Martin R Gaudinski, M.D. principal investigator

National Institute of Allergy and Infectious Diseases (NIAID)

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing VRC-HIVMAB075-00-AB in people with HIV Prevention, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 18 inclusion and 8 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 26 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2019). 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 Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Any Product Administration (time frame: 3 days after each product administration). The study lists 4 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 NCT03015181, which also lists 3 linked publications.

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 26 Oct 2020.