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Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously to Healthy Adults

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ClinicalTrials.gov Identifier: NCT03538626
Recruitment Status : Recruiting
First Posted : May 28, 2018
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:

Background:

Human Immunodeficiency Virus (HIV) infection is a serious disease. It has no cure or vaccine to prevent it. Using antibodies is one way to prevent HIV infection that seems promising. Antibodies are naturally made by the body to fight germs so people stay healthy. Researchers want to see if the antibody N6LS, made artificially in the lab, can prevent HIV infection.

Objective:

To see if the antibody N6LS is safe and well-tolerated.

Eligibility:

Healthy people ages 18-50

Design:

Participants will be assigned to 1 of 6 groups.

Group 1-4 participants will have about 13 visits over about 24 weeks. They will get N6LS once.

Group 5-6 participants will have about 26 visits over about 48 weeks. They will get N6LS 3 times.

Visits that involve receiving N6LS may be up to 8 hours. Follow up visits are about 30 minutes. Female participants will have pregnancy tests at each one.

Some participants will get N6LS through a thin tube in an arm vein. A pump will give N6LS directly into the vein for about 30 minutes. A tube in a vein in the other arm will collect blood.

Some participants will get the antibody as an injection into the fatty tissue of the belly, arm, or thigh.

Participants will have blood taken at every visit.

Participants will get a measuring tool and thermometer. They will check their temperature every day for 3 days after they get N6LS. They will check the injection site and measure any redness, swelling, or bruising.

Non-N6LS visits will be about 2 hours. Participants will report any health changes and how they have been feeling.


Condition or disease Intervention/treatment Phase
HIV Antibodies Biological: VRC-HIVMAB091-00-AB Phase 1

Detailed Description:

VRC 609: APhase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously to Healthy Adults

Study Design:

This is the first study in healthy adults of the N6LS monoclonal antibody (MAb). It is a dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics (PK) of N6LS. The hypothesis is that N6LS administration to healthy adults will be safe by the intravenous (IV) and subcutaneous (SC) routes. A secondary hypothesis is that N6LS will be detectable in human sera with a definable half-life.

Product Description:

N6LS (VRC-HIVMAB091-00-AB ) is a human MAb targeted to the HIV-1 CD4 binding site. It was developed by the VRC/NIAID/NIH and manufactured under current Good Manufacturing Practice (cGMP) regulations at the VRC Vaccine Pilot Plant operated under contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick, MD. The product is provided as a sterile aqueous buffered solution in 10 mL glass vials at a concentration of 100 +/- 10 mg/mL and volume of 6.25 +/- 0.10 mL.

Subjects: Healthy adults, 18-50 years of age.

Study Plan:

This open-label study will include 6 dose groups to assess N6LS given as a single IV infusion at the 5, 20, or 40 mg/kg dose level (Groups 1, 3,4); a single SC injection at the 5 mg/kg dose level (Group 2); or in 3 administrations, 12 weeks apart by SC injection at the 5 mg/kg dose level (Group 5), or by IV infusion at the 20 mg/kg dose level (Group 6). Enrollments will initially open with Groups 1, 2 and 5; followed by the sequential activation of Groups 3, 4, and 6.

Study Duration:

Subject study participation will be approximately 24 weeks for subjects in Groups 1 to 4 and 48 weeks for subjects in Groups 5 and 6.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRCHIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously to Healthy Adults (VRC 609)
Actual Study Start Date : June 21, 2018
Estimated Primary Completion Date : July 31, 2019
Estimated Study Completion Date : May 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: 1
5 mg/kg IV
Biological: VRC-HIVMAB091-00-AB
N6LS

Experimental: 2
5 mg/kg SC
Biological: VRC-HIVMAB091-00-AB
N6LS

Experimental: 3
20 mg/kg IV
Biological: VRC-HIVMAB091-00-AB
N6LS

Experimental: 4
40 mg/kg IV
Biological: VRC-HIVMAB091-00-AB
N6LS




Primary Outcome Measures :
  1. To evaIuate the safety and tolerabiIity of N6LS administered as a single dose at 5 mg/kg IV, 20 mg/kg IV, 40 mg/kg IV,or 5 mg/kg SC to heaIthy aduIts [ Time Frame: Day O to week 24 ]
  2. To evaluate the safety and tolerability of N6LSa dministered at 5mg/kg SC or 20mg/kg IV by repeat dosing every 12 weeks for a total of 3 injections/infusions in healthy adults. [ Time Frame: Day 0 to week 48 ]

Secondary Outcome Measures :
  1. To evaluate the pharmacokinetics of N6LS at each dose level through 24 weeks after the last dose. [ Time Frame: Day 0 to week 24 ]
  2. To determine whether anti-drug antibody (ADA) to N6LS can be detected in sera of N6LS recipients atbaseline, 4-weeks post each product administration, and at the last study visit. [ Time Frame: Day 0 to week 48 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

A subject must meet all of the following criteria:

  1. Willing and able to complete the informed consent process.
  2. 18 to 50 years of age.
  3. Based on history and examination, must be in good general health and without history of any of the conditions listed in the exclusion criteria.
  4. Willing to have blood samples collected, stored indefinitely, and used for research purposes.
  5. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  6. Screening laboratory criteria within 84 days prior to enrollment must meet the following criteria:

    • White blood cell count (WBC): 2,500-12,000/mm(3).
    • WBC differential: 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 or accompanied by PI or designee approval.
    • Creatinine: less than or equal to 1.1 x Upper Limit of Normal (ULN).
    • ALT: less than or equal to 1.25 x ULN.
    • AST: less than or equal to 1.25 x ULN.
    • Negative for HIV infection by an FDA approved method of detection.

    Female-Specific Criteria:

  7. 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.
  8. 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 subject will be excluded if one or more of the following conditions apply:

  1. Prior receipt of licensed or investigational monoclonal antibody.
  2. Weight > 115 kg.
  3. Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis within the 2 years prior to enrollment that has a reasonable risk of recurrence during the study.
  4. Hypertension that is not well controlled.
  5. Woman who is breast-feeding, or planning to become pregnant during the study participation.
  6. Receipt of any investigational study agent within 28 days prior to enrollment.
  7. Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the subject 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.

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): NCT03538626


Contacts
Contact: Jamie G Saunders, R.N. (301) 451-8715 saundersjg@niaid.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   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Martin R Gaudinski, M.D. National Institute of Allergy and Infectious Diseases (NIAID)

Additional Information:
Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03538626     History of Changes
Other Study ID Numbers: 180105
18-I-0105
First Posted: May 28, 2018    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 9, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Immune Cells
bNAb
Plasma Cell
HIV
Immunotherapy

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