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

NCT03015181 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17003017-I-0030
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

HIV Prevention

Keywords

Broadly Neutralizing; HIV Prevention; Anti-Drug Antibody; HIV-1; Immune Response

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Through 24 weeks after the last product administration

Secondary Outcomes (12)

• Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Single Dose Groups

  Up to 24 weeks post product administration

• Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Multiple Dose Groups

  Through 24 weeks after the last product administration

• Time to Reach Maximum Observed Serum Concentration (Tmax) of VRC07-523LS

  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

  Week 4 post product administration

• 12 Week Mean Serum Concentration of VRC07-523LS: Single Dose Groups

  Week 12 post product administration

Study Arms (7)

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.

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.

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.

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.

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.

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.

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.

Biological: VRC-HIVMAB075-00-AB

Interventions

VRC-HIVMAB075-00-AB BIOLOGICAL

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

Also known as: VRC07-523LS

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A volunteer must meet all of the following criteria:
• Able and willing to complete the informed consent process.
• to 50 years of age.

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 25142607 BACKGROUND

• 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.

  PMID: 20616233 BACKGROUND

• 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.

  PMID: 31473167 RESULT

Results Point of Contact

• Title: Martin Gaudinski, MD
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

martin.gaudinski@nih.gov

301-451-8715

Study Officials

• Martin R Gaudinski, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2017
• First Posted: January 9, 2017
• Study Start: February 21, 2017
• Primary Completion: July 10, 2018
• Study Completion: July 10, 2018
• Last Updated: October 26, 2020
• Results First Posted: July 11, 2019

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)