NCT03147859

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
10

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Nov 2017

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 3, 2017

Completed
1 month until next milestone

First Posted

Study publicly available on registry

May 10, 2017

Completed
6 months until next milestone

Study Start

First participant enrolled

November 1, 2017

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2023

Completed
Last Updated

May 11, 2023

Status Verified

May 1, 2023

Enrollment Period

6.2 years

First QC Date

April 3, 2017

Last Update Submit

May 10, 2023

Conditions

Outcome Measures

Primary Outcomes (1)

  • Vedolizumab safety and tolerance

    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0, with their timing of onset and resolution.

    6 months vedolizumab treatments, serial assessments over 12 months

Secondary Outcomes (2)

  • PVL rebound and remission after ATI on vedolizumab treatment, and after discontinuation of vedolizumab.

    serial phlebotomy measures over 12 months

  • PVL sustained rebound after ATI, and re-suppression on ART.

    serial phlebotomy measures over 12 months

Study Arms (3)

Group A-150mg dose of vedolizumab per infusion followed by ATI - Low Dose

EXPERIMENTAL

\* Please note that the previous low dose arm was 75mg of vedolizumab per infusion, but no participant was ever given this dose. The study will have a 20-week treatment phase and a 28-week follow-up phase over one year. Intravenous infusion of 150 mg of vedolizumab per infusion per visit schedule will be administered to 4 participants. The visit schedule will be the same for each group - Infusion at weeks 0, 2, 5, 8 and every 4 weeks thereafter up to 40 weeks for at least 7 doses as tolerated. ATI will begin between weeks 6 and 7, and infusions continued at weeks 8, 12, 16 and 20.

Biological: Vedolizumab (brand name Entyvio)

Group B-300mg dose of vedolizumab per infusion followed by ATI - Mid Dose

EXPERIMENTAL

The study will have a 20-week treatment phase and a 28-week follow-up phase over one year. Intravenous infusion of 300 mg of vedolizumab per infusion per visit schedule will be administered to 4 participants. The visit schedule will be the same for each group - Infusion at weeks 0, 2, 5, 8 and every 4 weeks thereafter up to 40 weeks for at least 7 (and up to 12) doses as tolerated. ATI will begin between week 10, and infusions continued at weeks 12, 16 and 20. Infusions may also be given at weeks 24, 28, 32, 36 and 40 depending on tolerance and pVL response.

Biological: Vedolizumab (brand name Entyvio)

Group C-600mg dose of vedolizumab per infusion followed by ATI - High Dose

EXPERIMENTAL

The study will have a 20-week treatment phase and a 28-week follow-up phase over one year. Intravenous infusion of 600 mg of vedolizumab per infusion per visit schedule will be administered to 4 participants. The visit schedule will be the same for each group - Infusion at weeks 0, 2, 5, 8 and every 4 weeks thereafter up to 40 weeks for at least 7 (and up to 12) doses as tolerated. ATI will begin between week 10, and infusions continued at weeks 12, 16 and 20. Infusions may also be given at weeks 24, 28, 32, 36 and 40 depending on tolerance and pVL response.

Biological: Vedolizumab (brand name Entyvio)

Interventions

IV infusion

Group A-150mg dose of vedolizumab per infusion followed by ATI - Low DoseGroup B-300mg dose of vedolizumab per infusion followed by ATI - Mid DoseGroup C-600mg dose of vedolizumab per infusion followed by ATI - High Dose

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Ottawa Hospital -General Campus

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Related Publications (2)

  • Barros PO, Burke Schinkel SC, Nayak AL, Haas B, Berthoud TK, McGuinty M, Cameron DW, Angel JB. Failure of gammadelta T Cell Recovery in the Gut With Effective Anti-HIV Therapy. J Immunol Res. 2025 Nov 27;2025:9883892. doi: 10.1155/jimr/9883892. eCollection 2025.

  • McGuinty M, Angel JB, Cooper CL, Cowan J, MacPherson PA, Kumar A, Murthy S, Sy R, Dennehy M, Tremblay N, Byrareddy SN, Cameron DW. Vedolizumab treatment across antiretroviral treatment interruption in chronic HIV infection: the HAVARTI protocol for a pilot dose-ranging clinical trial to assess safety, tolerance, immunological and virological activity. BMJ Open. 2020 Oct 8;10(10):e041359. doi: 10.1136/bmjopen-2020-041359.

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Bill Cameron, MD

    Ottawa Hospital Research Institute

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Bill Cameron, MD

CONTACT

Michaeline McGuinty, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 3, 2017

First Posted

May 10, 2017

Study Start

November 1, 2017

Primary Completion

December 31, 2023

Study Completion

December 31, 2023

Last Updated

May 11, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will share

Study dataset, after study closure and publication, by request.

Locations