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Safety and Virologic Effect of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), With Broad HIV-1 Neutralizing Activity, Administered Intravenously to HIV-Infected Adults

This study is currently recruiting participants.
Verified July 12, 2017 by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02840474
First Posted: July 21, 2016
Last Update Posted: October 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
  Purpose

Background:

The human body uses antibodies as one way to help fight infection. VRC01LS is an antibody directed against the HIV virus. Researchers want to see if it is safe and well tolerated. They will study the amount of VRC01LS in the body and how it changes over time. They will check to see if people who get VRC01LS develop an immune response to it.

Objective:

To see if VRC01LS is safe and well tolerated.

Eligibility:

Adults ages 18 70 who are HIV infected but otherwise healthy. Females who are able to get pregnant must be willing to use birth control during the study.

Design:

Participants will be screened in another protocol.

Participants will get the study drug one time, by IV infusion. A needle will guide a thin tube into a vein. The study drug mixed with salt water will be dripped into the vein over about 30 minutes.

Participants will be monitored for 30 minutes after the infusion.

Blood samples will be taken at the following times:

Once before the infusion

5 times in the 4 hours after the infusion

1 time 24 hours after infusion. Some participants may have 3 optional blood draws in the time period between 4 and 24 hours.

For 3 days after the infusion, participants will write their temperature and symptoms in a diary.

There will be a total of 23 study visits over 48 weeks. Ten visits will be in the first 4 weeks. At all visits, participants will answer health questions and give blood samples.


Condition Intervention Phase
HIV-1 Biological: VRC-HIVMAB080-00-AB (VRC01LS) Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: VRC 607: A Phase 1, Single Dose Study of the Safety and Virologic Effect of a Human MonoclonalAntibody, VRC-HIVMAB080-00-AB (VRC01LS), With Broad HIV-1 Neutralizing Activity, Administered Intravenously to HIV-Infected Adults.

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

Primary Outcome Measures:
  • To evaluate the safety and tolerability of VRC01LS administered at 40 mg/kg IV to HIV-1 infected viremic adults. [ Time Frame: Through 48 weeks of study participation. ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetics of VRC01LS at 40 mg/kg IV. [ Time Frame: Through the first 48 weeks post administration. ]
  • To evaluate the effect on CD4 count and viral load. [ Time Frame: Through week 48. ]
  • To determine whether anti-drug antibody (ADA) to VRC01LS can bedetected. [ Time Frame: Post administration ]

Estimated Enrollment: 20
Study Start Date: July 19, 2016
Estimated Study Completion Date: May 1, 2019
Estimated Primary Completion Date: May 1, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
40 mg/kg IV
Biological: VRC-HIVMAB080-00-AB (VRC01LS)
VRC01LS is an investigational human monoclonal antibody targeted to the CD4 binding site of HIV-1. VRC01LS is a modification of the VRC01 monoclonal antibody with the addition of the "LS".

Detailed Description:

VRC 607: A Phase 1, Single Dose Study of the Safety and Virologic Effect of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), with Broad HIV-1 Neutralizing Activity, Administered Intravenously to HIV-Infected Adults.

Study Design:

This is the first study of the VRC-HIVMAB080-00-AB (VRC01LS) monoclonal antibody (MAb) in HIV-infected viremic adults. It is a study to examine safety, tolerability, pharmacokinetics (PK) and virologic impact of VRC01LS. The primary hypothesis is that VRC01LS is safe for intravenous administration to HIV-1-infected adults and will not elicit hypersensitivity reactions. The secondary hypothesis is that VRC01LS will be detectable in human sera with a definable half-life.

Product Description:

VRC-HIVMAB080-00-AB (VRC01LS) is a human MAb targeted to the CD4 binding site of HIV-1. VRC01LS is a modification of the VRC01 MAb (which has been shown to be safe and to have antiviral activity in human studies) with the addition of the LS , a 2-amino acid mutation designed to improve the half-life of the antibody. There are no changes to the Fab binding sites. It was developed and manufactured by VRC/NIAID/NIH under cGMP at the VRC Vaccine Pilot Plant operated under contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick, MD. Vials are provided at 100 mg/mL.

Subjects:

HIV-1-infected viremic adults; 18-70 years of age.

Study Plan:

This is an open-label, single dose study to assess VRC01LS administered at 40 mg/kg IV in HIVinfected viremic subjects. Safety lab samples, HIV viral load, CD4 count, PK samples and blood samples for human anti-VRC01LS antibody detection will be drawn at baseline and intervals throughout the study. Subjects will keep a daily diary of reactogenicity symptoms for the 3 days after

study product administration and will be queried at each study visit for adverse events.

VRC 607 Study Schema:

Subjects-10 (*The expected enrollment is 10 subjects. Up to 20 subjects may be enrolled in

the event that there are subjects who do not complete the sampling schedule, if additional PK evaluations are needed, or if additional subjects are needed for safety evaluations)

Administration Schedule-Day 0; 40 mg/kg IV

Study Duration: Subjects will be followed for 48 weeks after the study product administration.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

A volunteer must meet all of the following criteria:

  1. Able and willing to complete the informed consent process.
  2. 18-70 years old
  3. Available for clinic visits for 48 weeks after study product administration.
  4. HIV-1 infected and clinically stable.
  5. No change in ARV regimen for the past 12 weeks prior to enrollment whether on or off ARVs
  6. At least one plasma viral load >=500 copies/mL and a detectable most recent plasma viral load within 28 days prior to enrollment. (Note: subjects must have a screening viral load less than or equal to 100,000 copies/mL. Outside laboratory results will be acceptable.)
  7. A CD4 count >= 350 cells/mcL on two of three consecutive testing occasions (or on two of two sequential test) within 28 days prior to enrollment. (Note: outside laboratory results will be acceptable.)
  8. In general good health as assessed by a study clinician and under the care of a primary health care provider for medical management of HIV infection while participating in the study. Willing to give consent to contact and send laboratory results to, the subject s primary health provider.
  9. Willing to have blood samples collected, stored indefinitely, and used for various research purposes.
  10. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  11. Screening laboratory values within 28 days prior to enrollment must meet the following criteria:

    • Absolute neutrophil count greater than or equal to 800/mcL
    • Platelets greater than or equal to 100,000/mcL
    • Hemoglobin greater than or equal to 10.0 gm/dL
    • Creatinine less than or equal to 1.31 mg/dL
    • Alanine aminotransferase (ALT) less than or equal to 2.5 x ULN
    • Negative Hepatitis B Surface Antigen
    • Undetectable Hepatitis C Viral Load

    Female-Specific Criteria:

  12. If a woman is sexually active with a male partner and has no history of hysterectomy, tubal ligation, or menopause, she must agree to use either a prescription birth control method or a barrier birth control method from the time of study enrollment until the last study visit, or have a monogamous partner who has had a vasectomy.
  13. Negative Beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential.

EXCLUSION CRITERIA:

A volunteer will be excluded if one or more of the following conditions apply:

  1. Previous receipt of humanized or human monoclonal antibody whether licensed or investigational.
  2. Ongoing AIDS-related opportunistic infection (including oral thrush).
  3. Active drug or alcohol use or dependence in the opinion of the site investigator that would interfere with adherence to study requirements.
  4. Any history of a severe allergic reaction including generalized urticaria, angioedema or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the study.
  5. Physical finding on examination considered clinically significant.
  6. Hypertension that is not well controlled.
  7. Breast-feeding.
  8. Receipt of any investigational study agent within 28 days prior to enrollment.
  9. Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02840474


Contacts
Contact: VRC Clinic (301) 451-8715 vaccines@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: VRC Clinic    301-451-8715    vaccines@nih.gov   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104-6056
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Grace L Chen, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02840474     History of Changes
Other Study ID Numbers: 160147
16-I-0147
First Submitted: July 19, 2016
First Posted: July 21, 2016
Last Update Posted: October 19, 2017
Last Verified: July 12, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
HIV Viral Load
Antiviral
CD4 Count
HIV-1 Infection

Additional relevant MeSH terms:
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs