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Evaluating the Safety, Tolerability, and Effect of a Human Monoclonal Antibody (VRC01) on Markers of HIV Persistence in HIV-Infected Adults Receiving Antiretroviral Therapy (ART)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02411539
First received: April 2, 2015
Last updated: November 9, 2016
Last verified: November 2016
  Purpose
The purpose of this study is to evaluate the safety, tolerability, and effect of an experimental human monoclonal antibody (mAb), VRC-HIVMAB060-00-AB (VRC01), in adults infected with HIV who are receiving antiretroviral therapy (ART).

Condition Intervention Phase
HIV Infections
Biological: VRC01
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I Study to Evaluate the Safety, Tolerability, and Effect of a Human Monoclonal Antibody, VRC-HIVMAB060-00-AB (VRC01), on Markers of HIV Persistence in ART-treated, HIV-infected Adults

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Occurrence of Grade 3 or greater adverse event (AE) [ Time Frame: Measured through Week 30 ]
    Including signs/symptoms, lab toxicities, and/or clinical events that are possibly, probably, or definitely related to study treatment (as judged by the core team, blinded to treatment arm) at any time from the initial dose of VRC01 to end of study follow-up.

  • Cell-associated HIV-1 RNA/DNA ratio in total CD4+ cells [ Time Frame: Measured through Week 6 ]

Secondary Outcome Measures:
  • Plasma HIV-1 RNA by single copy assay (SCA) [ Time Frame: Measured through Week 30 ]
  • Cell-associated HIV-1 RNA level [ Time Frame: Measured through Week 30 ]
  • Cell-associated HIV-1 DNA level [ Time Frame: Measured through Week 30 ]
  • Cell-associated HIV-1 RNA/DNA ratio in total CD4+ cells [ Time Frame: Measured through Week 30 ]
  • Change in inducible virus recovery [ Time Frame: Measured through Week 30 ]
  • VRC01 antibody level [ Time Frame: Measured through Week 30 ]
  • Detectability of antibody to VRC01 as measured in serum [ Time Frame: Measured through Week 30 ]
  • Measurement of CD4+ T-cell counts [ Time Frame: Measured through Week 30 ]
  • Measurement of CD8+ T-cell counts [ Time Frame: Measured through Week 30 ]
  • Levels of T-cell activation [ Time Frame: Measured through Week 30 ]
    % CD4+ and CD8+ T-cells co-expressing human leukocyte antigen (HLA)-DR and CD38

  • Levels of NK cell activation [ Time Frame: Measured through Week 30 ]
    % NK cells expressing CD69 or CD95

  • Plasma levels of sCD163 [ Time Frame: Measured through Week 30 ]
  • Plasma levels of sCD14 [ Time Frame: Measured through Week 30 ]
  • Plasma levels of interleukin-6 (IL-6) [ Time Frame: Measured through Week 30 ]
  • Plasma levels of human soluble tumor necrosis factor alpha-receptor (sTNFαR) [ Time Frame: Measured through Week 30 ]
  • Plasma levels of tumor necrosis factor alpha (TNFα) [ Time Frame: Measured through Week 30 ]
  • Plasma levels of high-sensitivity C-reactive protein (hsCRP) [ Time Frame: Measured through Week 30 ]
  • Premature treatment discontinuation for reasons related to study treatment [ Time Frame: Measured through Week 30 ]

Enrollment: 40
Study Start Date: May 2015
Study Completion Date: September 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: VRC01 followed by placebo
Participants will receive an infusion of VRC01 at Day 0 and Week 3 and an infusion of placebo at Weeks 6 and 9.
Biological: VRC01
40 mg/kg of VRC01 will be administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump
Other Name: VRC-HIVMAB060-00-AB
Biological: Placebo
Administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump
Experimental: Arm B: placebo followed by VRC01
Participants will receive an infusion of placebo at Day 0 and Week 3 and an infusion of VRC01 at Weeks 6 and 9.
Biological: VRC01
40 mg/kg of VRC01 will be administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump
Other Name: VRC-HIVMAB060-00-AB
Biological: Placebo
Administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump

Detailed Description:

Monoclonal antibodies (mAbs) have been developed as treatment for a variety of conditions including cancer, autoimmune disorders, and infections. mAbs may also be a potential treatment for people infected with HIV. The purpose of this study is to evaluate the safety and tolerability of an experimental human mAb, VRC-HIVMAB060-00-AB (VRC01), in HIV-infected adults receiving ART. Study researchers will also evaluate the effect of VRC01 on the number of infected cells containing unspliced HIV-1 transcripts in the blood in participants.

This study will enroll HIV-infected people 18 to 65 years old, who have been receiving ART for at least 2 years and who have a CD4+ count of 200 cells/mm^3 or greater. Participants will be randomly assigned to Arm A or Arm B. Participants in Arm A will receive an intravenous (IV) infusion of VRC01 at Day 0 and Week 3 and an IV infusion of placebo at Weeks 6 and 9. Participants in Arm B will receive an IV infusion of placebo at Day 0 and Week 3 and an IV infusion of VRC01 at Weeks 6 and 9. Participants will record their temperature and symptoms for 3 days after each infusion. Study visits will occur at study entry (Day 0), and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, and 30. Study visits will include physical examinations, clinical assessments, and blood collection.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection, documented by any FDA-approved 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 or E/CIA tests, or by HIV-1 antigen, or plasma HIV-1 RNA assay. More information on this criterion is available in the protocol.
  • Receiving continuous ART for at least 2 years (defined as no interruptions longer than 14 consecutive days) and with no changes in the components of the ART for at least 90 days prior to study entry
  • CD4+ cell count greater than or equal to 200 cells/mm^3 obtained within 60 days prior to study entry in a clinical laboratory improvement amendments (CLIA)-certified laboratory
  • Plasma HIV-1 RNA below the limit of detection of the FDA-approved assays (limit of detection: 75, 50, 40 or 20 copies/mL) for greater than or equal to 2 years on ART. Participants must have at least one documented HIV-1 RNA less than the limit of detection 12-24 months prior to study entry and at least one HIV-1 RNA less than the limit of detection within 12 months prior to study entry. All available HIV-1 RNA measurements must be below the assay limit of detection during the 2 years prior to study entry except as allowed by the following note. NOTE: A single unconfirmed plasma HIV-1 RNA greater than the limit of detection but less than 200 copies/mL within 6-24 months is allowed if followed by a subsequent value below the limit of detection.
  • Plasma HIV-1 RNA level of less than 40 copies/mL obtained by the Abbott Real-time HIV assay (m2000) or less than 20 copies/mL obtained by the Roche COBAS Taqman HIV-1 v2.0 assay within 60 days prior to entry
  • Men and women greater than or equal to 18 years of age and less than or equal to 65 years of age
  • The following laboratory values obtained within 60 days prior to entry by any U.S. laboratory that has a CLIA certification or its equivalent.

    • Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3
    • Hemoglobin greater than or equal to 11.0 g/dL for men and greater than or equal to 10.0 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. NOTE: A program for calculating creatinine clearance by the Cockcroft-Gault method is available on www.fstrf.org.
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (SGPT) less than or equal to 2.0 times upper limit of normal (ULN)
  • Hepatitis C virus (HCV) antibody negative result within 60 days prior to study entry or, if the HCV antibody result is positive, a negative HCV RNA result within 60 days prior to study entry
  • Negative HBsAg result obtained within 60 days prior to study entry
  • Ability and willingness of participant to provide informed consent
  • Females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or bilateral salpingectomy), will need a negative serum or urine pregnancy test within 48 hours prior to study entry. NOTE: Acceptable documentation of hysterectomy and bilateral oophorectomy, bilateral salpingectomy, tubal micro-inserts, partner who has undergone vasectomy, and menopause is participant-reported history.
  • All participants must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the participant/partner must use at least one reliable form of contraception (condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an intrauterine device (IUD); or hormone-based contraceptive), while receiving study treatment and for 12 weeks after stopping study treatment
  • Documentation of the availability of the following stored samples from the screening visit: peripheral blood mononuclear cell (PBMC) for CD4+ T-cell associated HIV-1 RNA, DNA assay and plasma for HIV-1 SCA. Sites must receive confirmation from the processing lab via phone, email, or fax, that specimens have been entered into the AIDS Clinical Trials Group (ACTG) Laboratory Data Management System (LDMS).

Exclusion Criteria:

  • Previous receipt of humanized or human monoclonal antibody (licensed or investigational)
  • Weight greater than 115 kg or less than 53 kg
  • Acute or ongoing AIDS-defining illness within 60 days prior to study entry
  • History of a severe allergic reaction with generalized urticarial, angioedema, or anaphylaxis within 2 years of study entry
  • Currently breastfeeding or pregnant
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Acute or serious illness that, in the opinion of the site investigator, requires systemic treatment and/or hospitalization within 60 days prior to entry
  • Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry. NOTE: Participants receiving stable physiologic doses of glucocorticoids, defined as the equivalent of prednisone less than or equal to 10 mg/day, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids will not be excluded.
  • Treatment for hepatitis C within 24 weeks of study entry
  • Vaccinations within 7 days prior to the screening, pre-entry, or study entry visits. NOTE: Participants are encouraged to get routine vaccinations, such as seasonal influenza vaccine more than 7 days prior to screening or between screening and pre-entry visits (outside of the 7-day window above).
  • Initiation of ART during acute HIV-1 infection (as determined by the site investigator by history and/or available medical records)
  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: NCT02411539

Locations
United States, California
UCSD Antiviral Research Center CRS
San Diego, California, United States, 92103
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins University CRS
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University Therapeutics (WT) CRS
St. Louis, Missouri, United States, 63110-1010
United States, New York
University of Rochester Adult HIV Therapeutic Strategies Network CRS
Rochester, New York, United States, 14642
United States, North Carolina
Chapel Hill CRS
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Ohio State University CRS
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, United States, 37204
United States, Texas
Houston AIDS Research Team CRS
Houston, Texas, United States, 77030
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104-9929
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Sharon Riddler, MD, MPH Pitt CRS
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02411539     History of Changes
Other Study ID Numbers: A5342
12003 ( Registry Identifier: DAIDS-ES )
Study First Received: April 2, 2015
Last Updated: November 9, 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, Monoclonal
Antibodies
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2017