NCT02599896

Brief Summary

Background: Antibodies help the body fight infection. VRC01LS is an antibody directed against HIV virus. HIV attacks the immune system. In animals, VRC01LS inactivated many types of HIV viruses. Researchers want to see if it does this in people. Objectives: To see if VRC01LS is safe and well-tolerated in people. To see what level of VRC01LS is maintained in people and if they develop an immune response to it. Eligibility: Healthy people ages 18 to 50 Design: Participants will be screened in protocol number VRC 500 (NIH 11-I-0164) with medical history, physical exam, and blood and urine tests. The study will last 24 to 48 weeks. Visits will last 2 to 8 hours. Participants will get VRC01LS through either:

  • A needle in an arm vein or
  • A small needle placed into the fatty tissue under the skin of the abdomen, thigh, or arm. Participants will be assigned to 1 of 6 groups. Groups 1 to 4 will get 1 dose of VRC01LS. They will have follow-up visits through week 24. Groups 5 and 6 will get 1 dose of VRC01LS every 12 weeks (3 doses). They will have 4 to 5 visits between the second and third dose, and follow-up visits through week 48. Participants will have 1 to 3 follow-up visits in the week after receiving VRC01LS. They will record their temperature and keep a diary of symptoms for 3 days after a dose. They may have additional unscheduled visits. At each visit, participants will have a physical exam and may have blood and urine tests.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
49

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Nov 2015

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 6, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 9, 2015

Completed
7 days until next milestone

Study Start

First participant enrolled

November 16, 2015

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 25, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 25, 2018

Completed
Last Updated

December 17, 2019

Status Verified

July 25, 2018

Enrollment Period

2.7 years

First QC Date

November 6, 2015

Last Update Submit

December 14, 2019

Conditions

Prevention of HIV InfectionHIV AntibodiesMonoclonal Antibody, HumanNeutralizing Antibody

Keywords

Dose EscalationHIV PreventionBroadly HIV-1 Neutralizing ActivityOpen-LabelHalf-Life

Outcome Measures

Primary Outcomes (3)

  • Evaluate the safety and tolerability of VRC-HIVMAB080-00-AB administered as a single dose at 5 mg/kg IV,20 mg/kg IV,40 mg/kg IV, and 5 mg/kg SC to healthy adults

    Through 24 weeks of study participation.

  • Evaluate the safety and tolerability of VRC-HIVMAB080-00-AB administered at 20 mg/kg IV by repeat dosing every 12 weeks for a total of 3 infusions to healthy adults.

    Through 48 weeks of study participation.

  • Evaluate the safety and tolerability of VRC-HIVMAB080-00-AB administered at 5 mg/kg SC by repeat dosing every 12 weeks for a total of 3 injections to healthy adults.

    Through 48 weeks of study participation.

Secondary Outcomes (2)

  • To evaluate the pharmacokinetics of VRC-HIVMAB080-00-AB at each dose level.

    Through 24 weeks after the last dose.

  • To determine whether anti-drug antibody (ADA) to VRC01LS can bedetected in recipients of VRC-HIVMAB080-00-AB.

    Through 24 weeks after the last dose.

Study Arms (8)

Group 1

EXPERIMENTAL

5 mg/kg/IV on Day 0

Biological: VRC-HIVMAB080-00-AB (VRC01LS)

Group 2

EXPERIMENTAL

5 mg/kg SC on Day 0

Biological: VRC-HIVMAB080-00-AB (VRC01LS)

Group 3

EXPERIMENTAL

20 mg/kg IV on Day 0

Biological: VRC-HIVMAB080-00-AB (VRC01LS)

Group 4

EXPERIMENTAL

40 mg/kg IV on Day 0

Biological: VRC-HIVMAB080-00-AB (VRC01LS)

Group 5

EXPERIMENTAL

5 mg/kg SC on Day 0, Week 12 and Week 24

Biological: VRC-HIVMAB080-00-AB (VRC01LS)

Group 6

EXPERIMENTAL

20 mg/kg IV on Day 0, Week 12 and Week 24

Biological: VRC-HIVMAB080-00-AB (VRC01LS)

Group 7

EXPERIMENTAL

5 mg/kg SC on Day 0, Week 4

Biological: VRC-HIVMAB060-00-AB (VRC01)

Group 8

EXPERIMENTAL

20 mg/kg IV on Day 0, Week 4

Biological: VRC-HIVMAB060-00-AB (VRC01)

Interventions

VRC-HIVMAB080-00-AB (VRC01LS)BIOLOGICAL

VRC01LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Group 1Group 2Group 3Group 4Group 5Group 6
VRC-HIVMAB060-00-AB (VRC01)BIOLOGICAL

VRC01 is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Group 7Group 8

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (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.
  • Screening laboratory values within 84 days prior to enrollment must meet the following criteria:
  • 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 to 400,000/mm(3).
  • Hemoglobin within institutional normal range.
  • Creatinine less than or equal to 1.1 x ULN.
  • 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 secually active with a male partner and has no history of hysterectomy, tubal ligation, or menopause, then she agrees to use either a prescription birth control method or barrier birth control method from the time of study enrollment until the last study visit, or to have a monogamous 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 monoclonal antibody whether licensed or investigational.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

  • 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: 20616233BACKGROUND

  • 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: 25142607BACKGROUND

  • Ko SY, Pegu A, Rudicell RS, Yang ZY, Joyce MG, Chen X, Wang K, Bao S, Kraemer TD, Rath T, Zeng M, Schmidt SD, Todd JP, Penzak SR, Saunders KO, Nason MC, Haase AT, Rao SS, Blumberg RS, Mascola JR, Nabel GJ. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature. 2014 Oct 30;514(7524):642-5. doi: 10.1038/nature13612. Epub 2014 Aug 13.

    PMID: 25119033BACKGROUND

  • Gaudinski MR, Coates EE, Houser KV, Chen GL, Yamshchikov G, Saunders JG, Holman LA, Gordon I, Plummer S, Hendel CS, Conan-Cibotti M, Lorenzo MG, Sitar S, Carlton K, Laurencot C, Bailer RT, Narpala S, McDermott AB, Namboodiri AM, Pandey JP, Schwartz RM, Hu Z, Koup RA, Capparelli E, Graham BS, Mascola JR, Ledgerwood JE; VRC 606 Study Team. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. PLoS Med. 2018 Jan 24;15(1):e1002493. doi: 10.1371/journal.pmed.1002493. eCollection 2018 Jan.

    PMID: 29364886DERIVED

MeSH Terms

Interventions

VRC01 monoclonal antibody

Study Officials

  • Martin R Gaudinski, M.D.

    National Institute of Allergy and Infectious Diseases (NIAID)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 6, 2015

First Posted

November 9, 2015

Study Start

November 16, 2015

Primary Completion

July 25, 2018

Study Completion

July 25, 2018

Last Updated

December 17, 2019

Record last verified: 2018-07-25

Locations

US(1)