Trial record 2 of 3 for:    VRC 500

Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), With Broad HIV-1 Neutralizing Activity, Administered Intravenously or Subcutaneously to Healthy Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT02599896
First received: November 6, 2015
Last updated: June 25, 2016
Last verified: June 2016
  Purpose

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.


Condition Intervention Phase
Prevention of HIV Infection
HIV Antibodies
Monoclonal Antibody, Human
Neutralizing Antibody
Biological: VRC-HIVMAB080-00-AB
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase 1, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), Administered Intravenously or Subcutaneously to Healthy Adults

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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 [ Time Frame: Through 24 weeks of study participation. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Through 48 weeks of study participation. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Through 48 weeks of study participation. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetics of VRC-HIVMAB080-00-AB at each dose level. [ Time Frame: Through 24 weeks after the last dose. ] [ Designated as safety issue: No ]
  • To determine whether anti-drug antibody (ADA) to VRC01LS can bedetected in recipients of VRC-HIVMAB080-00-AB. [ Time Frame: Through 24 weeks after the last dose. ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: October 2015
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
5 mg/kg/IV on Day 0
Biological: VRC-HIVMAB080-00-AB
VRC01LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.
Experimental: Group 2
5 mg/kg SC on Day 0
Biological: VRC-HIVMAB080-00-AB
VRC01LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.
Experimental: Group 3
20 mg/kg IV on Day 0
Biological: VRC-HIVMAB080-00-AB
VRC01LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.
Experimental: Group 4
40 mg/kg IV on Day 0
Biological: VRC-HIVMAB080-00-AB
VRC01LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.
Experimental: Group 5
5 mg/kg SC on Day 0, Week 12 and Week 24
Biological: VRC-HIVMAB080-00-AB
VRC01LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.
Experimental: Group 6
20 mg/kg IV on Day 0, Week 12 and Week 24
Biological: VRC-HIVMAB080-00-AB
VRC01LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.

Detailed Description:

VRC 606: A Phase 1, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), Administered Intravenously or

Subcutaneously to Healthy Adults

Study Design: This is the first study of the VRC-HIVMAB080-00-AB (VRC01LS) monoclonal antibody (MAb) in healthy adults. It is a dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics of VRC01LS. The hypothesis is that VRC01LS will be safe to administer to healthy adults by the intravenous (IV) and subcutaneous (SC) routes. 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 in human studies) with the addition of the LS , 2-amino acid mutation designed to improve the half-life of the antibody. It was developed by VRC/NIAID/NIH and manufactured under cGMP by the Vaccine Clinical Material Program operated for NIAID/VRC by Leidos Biomedical Research, Inc., Frederick, MD. Vials are provided at 100 mg/mL.

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

Study Plan: There are 4 open-label, dose escalation groups (Groups 1-4) to assess VRC01LS administered IV and SC once per subject and 2 open-label groups (Groups 5 and 6) to assess VRC01LS at 5 mg/kg SC or at 20 mg/kg IV administered every 12 weeks for a total of 3 administrations per subject.

Subjects will be randomized into Group 1 or Group 2 at a 1:1 ratio, or directly enrolled into Groups 3-6 per the dose escalation and safety evaluation plan. The study will begin with the 5 mg/kg dosage groups (Groups 1, 2 and 5). For each dose (5 mg/kg, 20 mg/kg and 40 mg/kg), following the first product administration, the study team will wait at least 2 days before administering VRC01LS to a second subject. Dose escalation, safety evaluation, and continued enrollments will be conducted in the same manner for each dose level.

Study Duration: Subjects will be followed for 24 weeks after the last study product administration.

  Eligibility

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

A volunteer must meet all of the following criteria:

  1. Able and willing to complete the informed consent process.
  2. 18 to 50 years of age.
  3. Based on history and examination, must be in general good health 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 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:

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

  1. Previous receipt of monoclonal antibody whether licensed or investigational.
  2. Weight > 115 kg.
  3. 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.
  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 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02599896

Contacts
Contact: Jamie G Saunders, R.N. Not Listed vaccines@NIH.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike 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: Julie E Ledgerwood, D.O. 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: NCT02599896     History of Changes
Other Study ID Numbers: 160018  16-I-0018 
Study First Received: November 6, 2015
Last Updated: June 25, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Dose Escalation
HIV Prevention
Broadly HIV-1 Neutralizing Activity
Open-Label
Half-Life

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2016