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.
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: March 15, 2014
Last verified: August 2013

September 21, 2013
March 15, 2014
August 2013
September 2016   (final data collection date for primary outcome measure)
To evaluate the safety and tolerability of VRC-HIVMAB060-00-AB administered at 1 mg/kg IV, 5mg/kg IV, 5 mg/kg SC, 20 mg/kg IV and 40 mg/kg IV on Day 0 and Week 4 to HIV-infected adults. [ Time Frame: October 2014 ] [ Designated as safety issue: Yes ]
To evaluate the safety and tolerability of VRC-HIVMAB060-00-AB administered at 1 mg/kg IV,5mg/kg IV,5 mg/kg SC, 20 mg/kg IV and 40 mg/kg IV on Day 0 and Week 4 to HIV-infected adults. [ Time Frame: October 2014 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01950325 on ClinicalTrials.gov Archive Site
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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...
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

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.

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 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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV-1 Infection
  • Neutralizing Antibody
  • Monoclonal Antibody
  • Viral Load
  • HIV Antibodies
Drug: VRC-HIVMAB060-00-AB
N/A
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
25
September 2016
September 2016   (final data collection date for primary outcome measure)
  • 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. 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.
Both
18 Years to 50 Years
No
Contact: Pamela Costner, R.N. (301) 451-8715 vaccines@nih.gov
United States
 
NCT01950325
130189, 13-I-0189
Not Provided
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Principal Investigator: Julie E Ledgerwood, D.O. National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health Clinical Center (CC)
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP