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Vedolizumab Treatment in Antiretroviral Drug Treated Chronic HIV Infection (HAVARTI)

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified May 2017 by Ottawa Hospital Research Institute
Sponsor:
Collaborators:
Children's Hospital of Eastern Ontario (CHEO) Research Institute
Nebraska Centre for Substance Abuse Research
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT03147859
First received: April 3, 2017
Last updated: May 11, 2017
Last verified: May 2017
  Purpose

Background:

In nearly all people with human immunodeficiency virus (HIV) infection, immunity cannot either control or eradicate the infection. There are good medicinal treatments, collectively called "ART" (antiretroviral therapy) which control HIV infection by suppressing the virus in the bloodstream. ART is needed for life, and if a person stops taking ART the HIV infection returns in the bloodstream. So, there is good treatment, but no cure. The researchers want to test whether a period of treatment with vedolizumab can be used to control HIV infection in the bloodstream in persons with HIV on ART, after stopping ART.

Objective:

To determine whether vedolizumab is safe and tolerable in people with HIV, to assess the safety of an analytical treatment interruption (ATI), and to determine whether vedolizumab can control HIV infection in the bloodstream without the use of ART.

Eligibility:

Adults 18-65 with HIV who are being treated with ART

Design:

Participants will be screened with: Physical exam, medical history, blood and urine tests Participants will have a baseline visit which will include repeat of the screening testing.

Participants will then present for their first study visit which will include: receiving vedolizumab infusions through an arm vein, repeats of the baseline testing. Participants will then have serial visits on a pre-specific schedule to receive ongoing vedolizumab doses every 2-4 weeks until week 20. Each visit will also include repeat of the baseline tests.

After week 6 and before week 7 patients will discontinue ART. After the final infusion of vedolizumab at week 20 patients will continue to be assessed with physical exam, medical history, and repeat of the baseline testing every 4 weeks up to 1 year.

ART will be re-started for participants if the level of HIV in the blood becomes too high, persists for too long, or if the CD4 count decreases by too much.


Condition Intervention Phase
HIV-infection/AIDS Biological: Vedolizumab (brand name Entyvio) Phase 2

Study Type: Interventional
Study Design: Intervention Model: Sequential Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Vedolizumab Treatment in Antiretroviral Drug Treated Chronic HIV Infection

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Vedolizumab safety and tolerance [ Time Frame: 6 months vedolizumab treatments, serial assessments over 12 months ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0, with their timing of onset and resolution.


Secondary Outcome Measures:
  • PVL rebound and remission after ATI on vedolizumab treatment, and after discontinuation of vedolizumab. [ Time Frame: serial phlebotomy measures over 12 months ]
    Quantitative PVL (Abbott HIV1 Viral Load Assay) measured serially during and after ATI.

  • PVL sustained rebound after ATI, and re-suppression on ART. [ Time Frame: serial phlebotomy measures over 12 months ]
    Quantitative PVL (Abbott HIV1 Viral Load Assay) measured serially during and after ATI.


Estimated Enrollment: 12
Anticipated Study Start Date: May 2017
Estimated Study Completion Date: December 21, 2018
Estimated Primary Completion Date: December 21, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: vedolizumab infusions and ATI
The study will have a 20-week treatment phase and a 28-week follow-up phase over one year. Intravenous infusion of vedolizumab will be administered in 3 groups of 4 participants at 75, 150 and 300 mg doses. The visit schedule will be the same for each group - Infusion at weeks 0, 2, 5, ATI will begin between weeks 6 and 7, and infusions continued at weeks 8, 12, 16 and 20, for a total of up to 7 doses.
Biological: Vedolizumab (brand name Entyvio)
IV infusion

Detailed Description:

HIV is a chronic active infection of lymphocytes and monocytoid cells resulting in a progressive and profound depletion of T cell subsets and ultimately in acquired immune deficiency syndrome (AIDS). HIV infects cells of the immune system throughout the body and may cause an active cytolytic infection in activated lymphocytes, become dormant as a latent infection in resting lymphocytes, or continue as a chronically active infection in macrophages. Continuous anti-retroviral drug treatment (ART) suppresses virus within the bloodstream and allows some degree of immune healing so as to permit near-normal health and life expectancy. However, interruption of ART is uniformly followed by rebound of viremia as a result of ongoing chronic active infection, and reactivation of latent infection. Successful ART requires daily medications indefinitely. There is an ongoing need for treatments which are more effective in the eradication of HIV. Counter to past expectations for cell-mediated immunity, broadly neutralizing monoclonal antibodies (nmAb) have been developed which show anti-HIV activity in vivo in reducing viremia (plasma virus load, PVL), and in slightly reducing recurrence of lasting PVL following analytical treatment interruption (ATI). Monoclonal antibody therapies against host cellular markers such as HIV co-receptors have been put forward as potential strategy in immunological treatment of HIV infection. If activated lymphocytes could be protected from cytolytic HIV infection in the presence of concurrent active HIV infection of other cells and tissues, then unperturbed potent acquired specific or innate immunity might confer lasting immunological remission of HIV infection.

This year, an unexpected finding of sustained remission of plasma viremia level (PVL) to below quantifiable assay limits in a rhesus macaque SIV infection model of AIDS was reported. The envelope of SIV (and HIV) appears to interact with α4β7 integrin, a lymphocyte homing receptor for trafficking to gut mucosal-associated lymphoid tissue (GALT) that was the target of mAb treatment in this study. This study showed that in animals treated with the mAb while discontinuing ART there was a diminished rebound and sustained remission of PVL, and less GALT associated viral load for a long-lasting period of at least 24 months. The mechanism of this unexpected post-treatment effect is unknown. In humans infected with HIV, such an effect sustained over time with continued remission of progressive immunodeficiency would meet definitional criteria of "functional cure" of HIV/AIDS. The results observed in the SIV model reveal a promising avenue for investigation in this area of research towards control of HIV infection in absence of ART. We propose to assess the safety and tolerability of anti-α4β7 integrin monoclonal antibody in healthy HIV-infected adults on ART, to assess the safety of ATI and whether anti-α4β7 integrin monoclonal antibody treatment can induce sustained virologic remission in the absence of ART.

  Eligibility

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

Inclusion Criteria:

  1. Adult (≥ 18 to 65 years) with HIV infection.
  2. Nadir CD4 T cell count ≥ 200 and current CD4 T cell count > 500 cells/mcL
  3. Adherent on ART 2 to 9 years with sustained pVL ≤ 50 copies/mL
  4. Ability to comprehend and provided informed consent

Exclusion Criteria:

  1. Past AIDS-defining or AIDS-related immune deficiency diseases
  2. Past drug-resistant HIV or ART-refractory pVL response
  3. Current hepatitis B or C virus infection, or untreated latent TB infection
  4. Clinically significant concurrent health condition.
  5. Pregnancy, lactation, or non-adherence with contraception if fertile.
  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: NCT03147859

Contacts
Contact: Bill Cameron, MD 613-737-8923 bcameron@toh.ca
Contact: Michaeline McGuinty, MD 289-668-3798 mimcguinty@toh.ca

Locations
Canada, Ontario
The Ottawa Hospital -General Campus
Ottawa, Ontario, Canada, K1H 8L6
Sponsors and Collaborators
Ottawa Hospital Research Institute
Children's Hospital of Eastern Ontario (CHEO) Research Institute
Nebraska Centre for Substance Abuse Research
Investigators
Principal Investigator: Bill Cameron, MD Ottawa Hospital Research Institute
  More Information

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT03147859     History of Changes
Other Study ID Numbers: 20160928-01H
Study First Received: April 3, 2017
Last Updated: May 11, 2017
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Study dataset, after study closure and publication, by request.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Vedolizumab
Gastrointestinal Agents

ClinicalTrials.gov processed this record on June 23, 2017