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Vedolizumab (Anti-alpha4beta7) in Subjects With HIV Infection Undergoing Analytical Treatment Interruption

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02788175
Recruitment Status : Completed
First Posted : June 2, 2016
Results First Posted : December 16, 2019
Last Update Posted : February 24, 2020
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information
First Submitted Date  ICMJE May 28, 2016
First Posted Date  ICMJE June 2, 2016
Results First Submitted Date  ICMJE November 25, 2019
Results First Posted Date  ICMJE December 16, 2019
Last Update Posted Date February 24, 2020
Study Start Date  ICMJE May 28, 2016
Actual Primary Completion Date March 4, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2020)
Number of Grade 2 or Higher Related Adverse Events [ Time Frame: From the start of the initial infusion until up to 72 weeks. ]
The primary endpoint was the number of grade 2 or higher adverse events, including serious adverse events, that were probably or definitely related to vedolizumab.
Original Primary Outcome Measures  ICMJE
 (submitted: May 28, 2016)
To evaluate the safety and tolerability of vedolizumab in HIV-infected individuals prior to and following analytical treatment interruption (ATI). [ Time Frame: Throughout ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2020)
Number of Subjects Who Met Criteria to Restart Antiretroviral Therapy Before Week 48 [ Time Frame: From Week 22 until up to 48 weeks. ]
The secondary endpoint was defined as number of subjects who experienced plasma viremia following ATI and met criteria to restart cART before week 48 [a confirmed >30% decline in baseline CD4+ T Cell count or an absolute CD4+ T Cell count in the setting of detectable HIV viremia (>40 copies/mL); a sustained (>4weeks) HIV RNA level of > 1000 copies/mL, or any HIV related symptoms or pregnancy.]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2016)
To evaluate the effect of vedolizumab administration on plasma viral rebound in HIV-infected individuals following ATI [ Time Frame: Throughout ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Vedolizumab (Anti-alpha4beta7) in Subjects With HIV Infection Undergoing Analytical Treatment Interruption
Official Title  ICMJE An Exploratory, Open-Label Study of Vedolizumab (Anti-alpha4beta7 Antibody) in Subjects With HIV Infection Undergoing Analytical Treatment Interruption
Brief Summary


In most people infected with human immunodeficiency virus (HIV), their immune system cannot control HIV infection. They need drugs called combination antiretroviral therapy (cART) to control the HIV. When people stop cART treatment, their immune system cannot control the infection again. They can also become resistant to cART and have lasting side effects. Researchers want to test if the drug vedolizumab is effective at controlling HIV infection without the need for cART.


To test if vedolizumab is safe and can control the amount of HIV in the blood when cART is not taken.


People ages 18-65 who have HIV and are being treated with cART


Participants will be screened with:

Physical exam

Medical history

Electrocardiogram: Soft, sticky patches on the chest, arms, and legs measure heart activity.

Blood and urine tests

Participants will have a baseline visit. This will be 2-5 hours each day for 1-2 days. It will include repeats of the screening tests and:

Leukapheresis: Blood is removed through a needle in the arm. A machine separates the white blood cells from the blood. The rest of the blood is returned to the participant.

Neurologic exam: The nerves and reflexes are tested.

First vedolizumab infusion through an arm vein

Participants will have visits every 4 weeks for 30 weeks. These will include:

Vedolizumab infusions

Repeats of baseline tests

Participants will have more visits for blood draws.

Participants will keep taking cART until after the week 22 infusion.

After discontinuing cART at study week 22, participants will be seen every two weeks to monitor the CD4 count and the level of HIV in the blood. Some of these visits will occur in between infusion visits and will only take about 1 hour to complete. cART will be restarted if a participant's HIV levels go up to high, or if their CD4 cell counts decreases by too much.

For the follow-up phase, participants will have visits every 4 weeks for 24 weeks. These will include blood tests and a physical exam.


Detailed Description While combination antiretroviral therapy (cART) has improved the clinical outcome for HIV-infected individuals, persistence of viral reservoirs in the peripheral blood and lymphoid tissues remains a hurdle to complete eradication of virus and cure of the infection. The concept that HIV preferentially infects discrete subsets of CD4+ T cells underscores the need to develop therapeutics that exploit specific cell-virus interactions. T cells expressing integrin alpha4beta7 not only regulate migration into the gut associated lymphoid tissue (GALT), but also concomitantly bind HIV, placing them in a prime position to disseminate HIV throughout the tissue. Previously, it has been shown that the HIV envelope protein gp120 binds to alpha4beta7 on CD4+ T cells in vitro, alpha4beta7high CD4+ T cells are highly susceptible to productive HIV infection in vitro, and the administration of anti-alpha4beta7 monoclonal antibody (mAb) prevents and/or delays transmission of SIV upon repeated challenges and preserves CD4+ T cells in rhesus macaques. Furthermore, it has been demonstrated that administration of anti-alpha4beta7 mAb in SIV-infected rhesus macaques receiving cART suppresses plasma viremia for extended periods following discontinuation of cART, collectively suggesting that sustained virologic remission in the absence of cART may be achieved via direct targeting of alpha4beta7 integrin. It is well established that the vast majority of HIV-infected individuals treated with cART experience plasma viral rebound within weeks of cessation of therapy. Considering that current research on the treatment of HIV-infected individuals has been heavily focused on developing strategies aimed at achieving sustained virologic remission in the absence of cART, it is of great interest to investigate whether administration of anti-alpha4beta7 mAb can prevent plasma viral rebound and allow durable suppression of viral replication in HIV infected individuals after discontinuation of cART. We propose to examine the effect of vedolizumab, an FDA approved anti-alpha4beta7 mAb for the treatment of ulcerative colitis and Crohn's disease, on plasma viral rebound in HIV-infected individuals following analytical treatment interruption (ATI).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV
Intervention  ICMJE Biological: Entyvio (Vedolizumab)
A humanized monoclonal antibody that specifically binds to the alpha4beta7 integrin with MAdCAM-1, which in turn inhibits the migration of T-lymphocytes across the endothelium into GALT
Study Arms  ICMJE Experimental: HIV-infected Adults on cART
HIV-infected Adults (age 18 - 65) on CART with suppressed viremia
Intervention: Biological: Entyvio (Vedolizumab)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 5, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: May 28, 2016)
Actual Study Completion Date  ICMJE March 4, 2019
Actual Primary Completion Date March 4, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  1. Age, 18 - 65 years
  2. Documented HIV-1 infection and clinically stable
  3. In general good health, 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
  4. CD4+ T cell count >450 cells/mm3 at screening
  5. Documentation of continuous cART treatment with suppression of plasma viral level below the limit of detection for more than or equal 2 years. Subjects with blips (i.e., detectable viral levels on cART) prior to screening may be included provided they satisfy the following criteria:

    1. The blips are <400 copies/mL, and
    2. Succeeding viral levels return to levels below the limit of detection on subsequent testing
  6. Willingness to undergo ATI
  7. Laboratory values within pre-defined limits at screening:

    • Absolute neutrophil count >1,000/mm3
    • Hemoglobin (Hgb) levels >10.0 g/dL for men and >9.0 g/dL for women
    • Platelet count >100,000/mm3
    • Prothrombin time (PT) and partial thromboplastin time (PTT) <1.5 upper limit of normal (ULN)
    • Estimated glomerular filtration rate (eGFR) of greater than or equal to 50 mL/min as determined by the NIH Clinical Center laboratory
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of <1.1 x ULN. Total bilirubin <1.1 x ULN (unless subject is taking atazanavir or has Gilbert s Syndrome)
  8. Willingness to have samples stored for future research

Participation of Women:

Contraception: The effects of vedolizumab on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.


  1. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.
  2. Documented nadir CD4+ T cell count <200 cells /mm3
  3. Documented multiclass antiretroviral drug resistance that, in the judgment of the investigator, would pose a risk of virologic failure should additional mutations develop during the study
  4. HIV immunotherapy or vaccine(s) received within 1 year prior to screening
  5. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment
  6. Receipt of other investigational study agent within 28 days of enrollment
  7. Any active malignancy that may require systemic chemotherapy or radiation therapy
  8. Systemic immunosuppressive medications received within 3 months prior to enrollment. The following are not excluded: [1] corticosteroid nasal spray or inhaler; [2] topical corticosteroids for mild, uncomplicated dermatitis; and [3] oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur (length of therapy less than or equal to 10 days, with completion in more than or equal to 30 days prior to enrollment)
  9. History or other clinical evidence of:

    • Significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent myocardial infarction)
    • Severe illness, chronic liver disease, malignancy, immunodeficiency other than HIV, active systemic infection other than HIV, or any other condition that, in the opinion of the investigator, would make the subject unsuitable for the study
    • Active or latent tuberculosis, regardless of treatment history
  10. Neurologic or neuropsychiatric disorder, the symptoms of which mimic PML and could interfere with the assessment of safety (e.g. history of encephalitis with motor sequela, stroke with sequela, severe major depressive disorder, severe bipolar disorder, seizure disorder)
  11. Active drug or alcohol abuse or any other pattern of behavior that, in the opinion of the investigator, would interfere with adherence to study requirements
  12. Pregnancy or breast-feeding

Co-enrollment Guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies. Study staff should be notified of co-enrollment as it will require the approval of the Principal Investigator.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02788175
Other Study ID Numbers  ICMJE 160118
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael C Sneller, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date March 4, 2019

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