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Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody (VRC01) in HIV-Infected Adults Undergoing a Brief Treatment Interruption

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02463227
First received: May 29, 2015
Last updated: May 6, 2016
Last verified: May 2016
  Purpose
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and antiviral activity of an antibody (called VRC01) in HIV-infected adults whose HIV is well-controlled with HIV medicines. The study will examine whether VRC01 controls or delays the return of HIV viremia when the participants' HIV medicines are briefly stopped during the study.

Condition Intervention Phase
HIV Infections
Biological: VRC01
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label Study of the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody, VRC-HIVMAB060-00-AB (VRC01), With Broad HIV-1 Neutralizing Activity, Administered Intravenously to HIV-Infected Adults Undergoing a Brief Analytical Treatment Interruption

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Occurrence of a Grade 3 or greater systemic (i.e., not a local reaction) adverse event (AE) that is possibly, probably, or definitely related to the administration of the VRC01 antibody [ Time Frame: Measured through week 21 ]
  • Confirmed HIV-1 RNA greater than or equal to 200 copies/mL at week 8 of the analytical treatment interruption (ATI) or indication to re-initiate ART prior to week 8 of the ATI [ Time Frame: Measured through week 8 of the ATI ]

Secondary Outcome Measures:
  • Measurement of Cmax in the plasma [ Time Frame: Measured through week 21 ]
  • Measurement of Cmin in the plasma [ Time Frame: Measured through week 21 ]
  • Measurement of AUC (area under the curve) in the plasma [ Time Frame: Measured through week 21 ]
  • Confirmed HIV-1 RNA greater than or equal to 200 copies/mL at week 4 of the ATI or indication to reinitiate ART prior to week 4 of the ATI [ Time Frame: Measured through week 4 of the ATI ]

Enrollment: 14
Study Start Date: July 2015
Study Completion Date: March 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VRC01
Participants will receive an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42.
Biological: VRC01

40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP.

Administered over about 30 to 60 minutes using a volumetric pump.

Other Name: VRC-HIVMAB060-00-AB

Detailed Description:

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and antiviral activity of a human monoclonal antibody, VRC-HIVMAB060-00-AB (known as VRC01), in HIV-infected adults whose HIV is well-controlled with antiretroviral therapy (ART). The study will examine whether VRC01 delays or prevents the return of HIV viremia in participants who are undergoing a brief analytical treatment interruption (ATI).

The study will enroll HIV-infected participants 18 years and older who are on ART. (ART will not be provided by the study). At a pre-entry study visit, participants will undergo blood collection, a leukapheresis procedure, and a rectal biopsy. The study will last about 34 weeks and proceed in three stages: Step 1 (approximately 9 weeks), Step 2 (approximately 12 weeks), and Step 3 (approximately 13 weeks).

During Step 1, participants will receive three doses of VRC01 via intravenous (IV) infusion. The first dose of VRC01 will be given on day 0. Seven days after receiving this first dose of VRC01, participants will discontinue ART. Participants will receive the second and third doses of VRC01 at days 21 and 42, respectively. For 7 days after each VRC01 IV infusion, participants will monitor and record their temperature and any symptoms. In addition to the 3 injection study visits, participants will attend weekly visits from day 7 through approximately day 63 (week 9).

Participants will enter Step 2 of the study and resume ART when they have a confirmed return of HIV-1 viremia or a confirmed CD4+ T-cell count of less than 350 cells/μL.

Step 2 study visits will occur on the day ART is resumed (Step 2, week 1) and every four weeks thereafter (approximately at Step 2, weeks 4, 8, and 12) until a participant's HIV viral load decreases to less than 50 copies/mL.

Throughout the study, visits will include clinical assessments and blood collection. Some blood will be stored for future testing. Some study visits will include the collection of oral, rectal, and (for women) cervical secretion samples. On day 63, participants will undergo another leukapheresis procedure and a rectal biopsy.

Participants who have completed Step 2 may optionally enter Step 3 for additional testing. Entry into Step 3 will occur at least 3 months after the participant has completed Step 2. Step 3 participants will have additional study visits for a leukapheresis procedure, a rectal biopsy, and clinical follow up.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Step 1 Inclusion Criteria:

  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load (VL). More information on this criterion can be found in the protocol.
  • Ability and willingness of participant or legal representative to provide informed consent
  • Men and women greater than or equal to 18 years old
  • Clinically stable on their first or second ART regimen that includes a boosted protease inhibitor or an integrase inhibitor. The current regimen should be stable for 8 weeks at the time of entry. Changes while the patient HIV viral load is undetectable does not count toward the number of ART regimens used, (for example an individual switching from a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen to an integrase inhibitor based regimen while the HIV viral load is undetectable will still be in their first regimen).
  • HIV-1 RNA that is less than 50 copies/mL using a Food and Drug Administration (FDA)-approved assay performed by any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent within 45 days prior to study entry
  • HIV-1 RNA less than 50 copies/mL using a FDA-approved assay for at least 24 weeks prior to study entry performed by any laboratory that has a CLIA certification or its equivalent. More information on this criterion can be found in the protocol.
  • Screening CD4+ T-cell count greater than or equal to 450 cells/μL within 45 days prior to study entry
  • Nadir CD4+ T-cell count greater than 200 cells/μL
  • Willingness to have blood samples collected, stored indefinitely, and used for study-related research purposes
  • The following laboratory values obtained within 45 days prior to enrollment:

    • Absolute neutrophil count (ANC) greater than or equal to 1000 cells/mm^3
    • Hemoglobin greater than or equal to 12.0 g/dL for men and greater than or equal to 11.0 g/dL for women
    • Platelet count greater than or equal to 100,000/mm^3
    • Creatinine clearance greater than or equal to 60 mL/min estimated by the Cockcroft-Gault equation. More information on this criterion can be found in the protocol.
    • Alanine aminotransferase (ALT) less than or equal to 2.0 times the upper limit of normal (ULN)
  • At least eight participants will have availability of plasma or serum specimen before the initiation of ART either in the Center for AIDS Research (CFAR) repository of the University of Pennsylvania, University of Alabama, or in the AIDS Clinical Trials Group (ACTG) central repository
  • For females of reproductive potential (i.e., women who have not been post-menopausal for at least 24 consecutive months; who have had menses within the preceding 24 months; or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy), negative urine pregnancy test (with a sensitivity of 15 to 25 mIU/mL) within 48 hours prior to screening and entry. More information on this criterion can be found in the protocol.
  • Contraceptive methods will be required for female participants of reproductive potential. Female participants of reproductive potential and their male partners MUST appropriately use at least two contraceptives, with one method being highly effective and the other method being either highly effective or less effective. More information on this criterion, including a list of acceptable contraceptive options, can be found in the protocol.
  • Contraceptive methods will be required for female partners of reproductive potential of male study participants on study drug. Female partners of reproductive potential of male study participants and/or their male partners MUST appropriately use at least two contraceptives, with one method being highly effective and the other method being either highly effective or less effective. More information on this criterion, including a list of acceptable contraceptive options, can be found in the protocol.
  • Negative hepatitis B surface antigen (HBsAg) result obtained within 6 months prior to study entry
  • Hepatitis C virus (HCV) antibody negative result within 6 months prior to entry, or if the HCV antibody result is positive, a negative HCV RNA obtained within 6 months prior to study entry
  • Adequate venous access in at least one arm

Step 2 Inclusion Criteria:

  • Entry into Step 1 of this study (A5340)
  • Receipt of at least one dose or partial dose of VRC01 in Step 1
  • Reinitiating ART for protocol or non-protocol-defined reasons. More information on this criterion can be found in the protocol.

Step 3 Inclusion Criteria:

  • Entry into and completion of Step 2 of this study (A5340) at least 3 months ago
  • HIV-1 RNA less than 50 copies/ml at pre-entry visit
  • Ability and willingness of participant or legal representative to provide informed consent
  • Willingness to have blood samples/specimens collected, stored indefinitely, and used for study-related research purposes
  • Adequate venous access in at least one arm

Step 1 Exclusion Criteria:

  • Previous receipt of humanized or human monoclonal antibody whether licensed or investigational
  • Weight greater than 115 kg or less than 53 kg
  • History of an AIDS-defining illness
  • Ongoing AIDS-related opportunistic infection (including oral thrush)
  • History of a severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis in the 2 years prior to enrollment
  • Currently breastfeeding
  • Receipt of other investigational study agent within 30 days prior to enrollment
  • Treatment with systemic glucocorticoids (e.g., prednisone or other glucocorticoid) or other immunomodulators (other than nonsteroidal anti-inflammatory drugs [NSAIDs]) within 30 days prior to enrollment
  • Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the participant, including, but not limited to diabetes mellitus type I, OR clinically significant forms of drug or alcohol abuse, severe asthma, autoimmune disease, uncontrolled hypertension, liver disease, psychiatric disorders, heart disease, or cancer
  • Treatment during acute infection (i.e., treatment within 6 months of acute infection)
  • Current use of a NNRTI

Step 2 Exclusion Criteria:

  • Non-participation in Step 1

Step 3 Exclusion Criterion:

  • Non-participation in Step 2
  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: NCT02463227

Locations
United States, Alabama
Alabama CRS
Birmingham, Alabama, United States, 35294
United States, Pennsylvania
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Pablo Tebas, MD University of Pennsylvania
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02463227     History of Changes
Other Study ID Numbers: A5340
11998 ( Registry Identifier: DAIDS ES Registry Number )
Study First Received: May 29, 2015
Last Updated: May 6, 2016

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
Antibodies, Monoclonal
Antiviral Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Infective Agents

ClinicalTrials.gov processed this record on March 30, 2017