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

NCT02788175 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 16011816-I-0118
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Background: 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. Objective: To test if vedolizumab is safe and can control the amount of HIV in the blood when cART is not taken. Eligibility: People ages 18-65 who have HIV and are being treated with cART Design: 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. ...

Conditions

HIV

Keywords

HIV Immune Therapy; Monoclonal Antibody; Integrin

Outcome Measures

Primary Outcomes (1)

• Number of Grade 2 or Higher Related Adverse Events

  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.

  From the start of the initial infusion until up to 72 weeks.

Secondary Outcomes (1)

• Number of Subjects Who Met Criteria to Restart Antiretroviral Therapy Before Week 48

  From Week 22 until up to 48 weeks.

Study Arms (1)

HIV-infected Adults on cART

EXPERIMENTAL

HIV-infected Adults (age 18 - 65) on CART with suppressed viremia

Biological: Entyvio (Vedolizumab)

Interventions

Entyvio (Vedolizumab) BIOLOGICAL

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

HIV-infected Adults on cART

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age, 18 - 65 years
• Documented HIV-1 infection and clinically stable
• 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
• CD4+ T cell count \>450 cells/mm3 at screening
• 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:
• The blips are \<400 copies/mL, and
• Succeeding viral levels return to levels below the limit of detection on subsequent testing
• Willingness to undergo ATI
• 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)

You may not qualify if:

• 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.
• Documented nadir CD4+ T cell count \<200 cells /mm3
• 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
• HIV immunotherapy or vaccine(s) received within 1 year prior to screening
• Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment
• Receipt of other investigational study agent within 28 days of enrollment
• Any active malignancy that may require systemic chemotherapy or radiation therapy
• 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)
• 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
• 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)
• 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
• Pregnancy or breast-feeding

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, Xiao Z, Veenstra TD, Conrad TP, Lempicki RA, McLaughlin S, Pascuccio M, Gopaul R, McNally J, Cruz CC, Censoplano N, Chung E, Reitano KN, Kottilil S, Goode DJ, Fauci AS. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008 Mar;9(3):301-9. doi: 10.1038/ni1566. Epub 2008 Feb 10.

  PMID: 18264102 BACKGROUND

• Cicala C, Martinelli E, McNally JP, Goode DJ, Gopaul R, Hiatt J, Jelicic K, Kottilil S, Macleod K, O'Shea A, Patel N, Van Ryk D, Wei D, Pascuccio M, Yi L, McKinnon L, Izulla P, Kimani J, Kaul R, Fauci AS, Arthos J. The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20877-82. doi: 10.1073/pnas.0911796106. Epub 2009 Nov 20.

  PMID: 19933330 BACKGROUND

• Byrareddy SN, Kallam B, Arthos J, Cicala C, Nawaz F, Hiatt J, Kersh EN, McNicholl JM, Hanson D, Reimann KA, Brameier M, Walter L, Rogers K, Mayne AE, Dunbar P, Villinger T, Little D, Parslow TG, Santangelo PJ, Villinger F, Fauci AS, Ansari AA. Targeting alpha4beta7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection. Nat Med. 2014 Dec;20(12):1397-400. doi: 10.1038/nm.3715. Epub 2014 Nov 24.

  PMID: 25419708 BACKGROUND

MeSH Terms

Interventions

vedolizumab

Results Point of Contact

• Title: Dr. Michael C. Sneller
• Organization: NIAID

MSNELLER@niaid.nih.gov

301-496-0491

Study Officials

• Michael C Sneller, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2016
• First Posted: June 2, 2016
• Study Start: May 28, 2016
• Primary Completion: March 4, 2019
• Study Completion: March 4, 2019
• Last Updated: February 24, 2020
• Results First Posted: December 16, 2019

Record last verified: 2019-03-04

Locations

US (1)