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

NCT ID: NCT03015181

Last Updated: 2020-10-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-21

Study Completion Date

2018-07-10

Brief Summary

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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.

Detailed Description

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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

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HIV Prevention

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group 1: 1 mg/kg IV Single Dose

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.

Group Type EXPERIMENTAL

VRC-HIVMAB075-00-AB

Intervention Type BIOLOGICAL

VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Group 2: 5 mg/kg IV Single Dose

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.

Group Type EXPERIMENTAL

VRC-HIVMAB075-00-AB

Intervention Type BIOLOGICAL

VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Group 3: 5 mg/kg SC Single Dose

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.

Group Type EXPERIMENTAL

VRC-HIVMAB075-00-AB

Intervention Type BIOLOGICAL

VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Group 4: 20 mg/kg IV Single Dose

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.

Group Type EXPERIMENTAL

VRC-HIVMAB075-00-AB

Intervention Type BIOLOGICAL

VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Group 5: 40 mg/kg IV Single Dose

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.

Group Type EXPERIMENTAL

VRC-HIVMAB075-00-AB

Intervention Type BIOLOGICAL

VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Group 6: 5 mg/kg SC Multiple Doses

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.

Group Type EXPERIMENTAL

VRC-HIVMAB075-00-AB

Intervention Type BIOLOGICAL

VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Group 7: 20 mg/kg IV Multiple Doses

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.

Group Type EXPERIMENTAL

VRC-HIVMAB075-00-AB

Intervention Type BIOLOGICAL

VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Interventions

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VRC-HIVMAB075-00-AB

VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Intervention Type BIOLOGICAL

Other Intervention Names

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VRC07-523LS

Eligibility Criteria

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Inclusion Criteria

A volunteer must meet all of the following criteria:

* Able and willing to complete the informed consent process.
* 18 to 50 years of age.

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.
* 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.


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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martin R Gaudinski, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 25142607 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20616233 (View on PubMed)

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.

Reference Type RESULT
PMID: 31473167 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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17-I-0030

Identifier Type: OTHER

Identifier Source: secondary_id

170030

Identifier Type: -

Identifier Source: org_study_id