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VRC 601: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC HIVMAB060-00-AB (VRC01), With Broad HIV-1 Neutralizing Activity, Administered Intravenously or Subcutaneously to HIV-Infected...

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 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:
NCT01950325
First received: September 21, 2013
Last updated: July 18, 2014
Last verified: August 2013
  Purpose

This is the first clinical trial of the VRC-HIVMAB060-00-AB (VRC01) monoclonal antibody. VRC01 is a broadly neutralizing antibody directed against HIV. This is a dose-escalation study to examine safety, tolerability, dose and pharmacokinetics of VRC01. The hypothesis is that VRC01 will be safe for administration to HIV-1 infected adults by the intravenous (IV) and subcutaneous (SC) routes and will not elicit hypersensitivity reactions. Samples will be collected to learn if VRC01 is detectable in mucosal secretions and blood of participants and how long VRC01 can be detected in the blood after it is given.

Between 15 and 25 HIV-1 infected adults, ages 18-50 years will be enrolled. There are 4 dose escalation groups for IV administration; the doses are 1 mg/kg, 5 mg/kg, 20 mg/kg and 40 mg/kg. There is 1 group for SC administration at 5 mg/kg. Each group is expected to include at least 3 participants. Each participant will receive two infusions of VRC01 with about 1 month between doses. Infusions are administered in an inpatient unit and an overnight stay at the NIH Clinical Center is required. No more than one subject per day per group will receive a first infusion of the VRC01 product by the IV route and no more than one subject per week will receive a first infusion of the product by the SC route. Study participation lasts for 24 weeks. Participant health and effect on CD4 count and HIV viral load will be monitored. Samples will be collected and stored for research purposes.


Condition Intervention Phase
HIV-1 Infection
Neutralizing Antibody
Monoclonal Antibody
Viral Load
HIV Antibodies
Biological: VRC-HIVMAB060-00-AB
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: VRC 601: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC HIVMAB060-00-AB (VRC01), With Broad HIV-1 Neutralizing Activity, Administered Intravenously or Subcutaneously to HIV-Infected Adults

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Adverse events of all severities [ Time Frame: From first product admin thru 56 days after last admin ] [ Designated as safety issue: Yes ]
  • Solicited systemic adverse events [ Time Frame: For 3 days after ea product admin ] [ Designated as safety issue: Yes ]
  • Serious adverse events and new chronic medical conditions requiring ongoing medical management [ Time Frame: From first product admin thru Study Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics at each dose level [ Time Frame: Thru 4 weeks after first dose and thru 8 wks after second dose ] [ Designated as safety issue: No ]
  • Assess whether anti-drug antibody can be detected in study agent recipients [ Time Frame: From first product admin thru Study Week 24 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: August 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
1mg/kg IV
Biological: VRC-HIVMAB060-00-AB
VRC01 Human Monoclonal Antibody
Experimental: Group 2 or Group 3
5 mg/kg IV (Group 2) or 5 mg/kg SC (Group 3)[only portion of the study that is randomized]
Biological: VRC-HIVMAB060-00-AB
VRC01 Human Monoclonal Antibody
Experimental: Group 4
20 mg/kg IV
Biological: VRC-HIVMAB060-00-AB
VRC01 Human Monoclonal Antibody
Experimental: Group 5
40 mg/kg IV
Biological: VRC-HIVMAB060-00-AB
VRC01 Human Monoclonal Antibody

Detailed Description:

This is the first clinical trial of the VRC-HIVMAB060-00-AB (VRC01) monoclonal antibody. VRC01 is a broadly neutralizing antibody directed against HIV. This is a dose-escalation study to examine safety, tolerability, dose and pharmacokinetics of VRC01. The hypothesis is that VRC 01 will be safe for administration to HIV-1- infected adults by the intravenous (IV) and subcutaneous (SC) routes and will not elicit hypersensitivity reactions. Samples will be collected to learn if VRC 01 is detectable in mucosal secretions and blood of participants and how long VRC01 can be detected in the blood after it is given.

Between15 and 30 HIV-1 infected adults, ages 18-60 years will be enrolled. There are 4 dose escalation groups for IV administration; the doses are 1 mg/kg, 5 mg/kg, 20 mg/kg and 40 mg/kg. There is 1 group for SC administration at 5 mg/kg. Each group is expected to include at least 3 participants. Each participant will receive two infusions of VRC01 with about 1 month between doses. Infusions are administered in an inpatient unit and an overnight stay at the NIH Clinical Center is required. No more than one subject per day per group will receive a first infusion of the VRC01 product by the IV route and no more than one subject per week will receive a first infusion of the product by the SC route. Study participation lasts for 24 weeks. Participant health and effect on CD4 count and HIV viral load will be monitored. Samples will be collected and stored for research purposes.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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 to 60 years of age.
  3. HIV infected and clinically stable, without changes in ARV status (whether or not taking an ARV regimen) in the 24 weeks prior to enrollment.
  4. Plasma viral load (VL) and CD4 count that meet eligibility criteria on at least two measurements performed within the 24 weeks prior to enrollment. The two measurements used for eligibility must have at least 3 days between tests and at least one set of the tests must be performed at the NIH Clinical Center within the 84 days prior to enrollment.

    For volunteers who are not on ARV treatment the criteria are:

    -VL less than or equal to 50,000 copies/mL and a CD4 count greater than or equal to 400/mcL.

    For volunteers on ARV treatment without a history of highly resistant virus the criteria are:

    -VL less than or equal to 50 copies/mL and a CD4 count greater than or equal to 3500/mcL.

    [Note: A viral blip of < 400 copies/mL during the 24 weeks prior to enrollment is permitted if preceded and followed by test results showing VL less than or equal to 50 copies/mL on the same ARV regimen.]

    For volunteers with highly drug resistant HIV who are on ARV therapy, the criteria are:

    -VL less than or equal to 20,000 copies/mL and a CD4 count greater than or equal to 250/mcL.

    [Note: Highly drug resistant HIV is defined in this protocol as:

    --genotype test results showing the presence of HIV with resistance to at least one drug in the following ARV classes: a) nucleoside reverse transcriptase inhibitor (NRTI); b) non-nucleoside reverse transcriptase inhibitor (NNRTI); and c) protease inhibitor (PI) resistance defined as greater than or equal to 3 major PI-associated mutations.

    OR

    --phenotype test results reporting resistance to at least one drug from the NRTI, NNRTI and PI classes.]

  5. In general good health and with an identified primary health care provider for medical management of HIV infection and willing to maintain a relationship with a primary health care provider for medical management of HIV infection while participating in the study.
  6. Willing to have blood samples collected, stored indefinitely, and used for various research purposes.
  7. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  8. Screening laboratory values within 84 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 2.0 times ULN

    Female-Specific Criteria:

  9. Agrees not to become pregnant from the time of study enrollment until the last study visit. If a woman is sexually active and has no history of hysterectomy or tubal ligation or menopause, she must agree to use a prescription birth control method or a barrier birth control method.
  10. Negative Beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for any women unless she is post-menopause for 24 consecutive months or has undergone a surgical procedure that precludes pregnancy.

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. Weight > 130 kg or < 53 kg.
  3. Detectable hepatitis B surface antigen (HBsAg) or hepatitis C viral load on tests performed within 84 days prior to enrollment.
  4. Ongoing AIDS-related opportunistic infection (including oral thrush)
  5. Active injection drug use within previous 12 months or active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  6. History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis in the 2 years prior to enrollment.
  7. Physical finding on examination considered clinically significant such as murmur (other than functional), hepatosplenomegaly, lymphadenopathy or focal neurological deficit.
  8. Hypertension that is not well controlled by medication.
  9. Breast-feeding.
  10. Receipt of other investigational study agent within 28 days prior to enrollment.
  11. 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, severe 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: NCT01950325

Contacts
Contact: Pamela Costner, R.N. (301) 451-8715 vaccines@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For additional information , please contact VRC Clinic    301-451-8715    vaccines@nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Julie E Ledgerwood, D.O. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT01950325     History of Changes
Other Study ID Numbers: 130189, 13-I-0189
Study First Received: September 21, 2013
Last Updated: July 18, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
HIV-1 Viral Load
CD4 Count
Antiviral
HIV-1 Infection
Broadly Neutralizing Antibody

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
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014